ANOTHER GLAXO FAILURE

EMEA has been formally notified by GSK of its decision to withdraw application for a centralised marketing authorisation for casopitant mesilate

23.10.09

Category: Scientific News

The drug was expected to be used in the prevention of chemotherapy-induced nausea and vomiting

The European Medicines Agency (EMEA) has been formally notified by GlaxoSmithKline Research and Development Limited of its decision to withdraw its application for a centralised marketing authorisation for the medicine Zunrisa (casopitant mesilate), 50 mg and 150 mg film coated tablets.

Zunrisa was expected to be used in the prevention of post-operative nausea and vomiting and chemotherapy-induced nausea and vomiting.

The application for the marketing authorisation for Zunrisa was submitted to the Agency on 2 July 2008. At the time of the withdrawal, it was under review by the Agency’s Committee for Medicinal Products for Human Use (CHMP).

In its official letter, the company stated that the withdrawal of the application was based on the company’s assessment that further safety data would be required to support the registration of casopitant on a worldwide basis and that it would take considerable time to produce these data. The company further stated that consequently all ongoing applications for authorisation are being withdrawn.

Withdrawal of an application does not prejudice the possibility of a company making a new application at a later stage.

A NOVEL TARGET FOR INFLAMMATORY BREAST CANCER

EGFR TKI reverses mesenchymal to epithelial phenotype and inhibits metastasis in inflammatory breast cancer

26.10.09

Category: Scientific News

Targeting EGFR through the ERK pathway may represent an effective therapeutic approach

Inflammatory breast cancer (IBC) is a rare but aggressive type of advanced breast cancer. Epidermal growth factor receptor (EGFR) expression is an independent poor prognostic factor in IBC. The purpose of the study, led by Dr Naoto T Ueno of the Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, USA was to determine the effect on IBC tumorigenicity and metastasis of blocking the EGFR pathway.

IBC cell lines, which express high level of EGFR, were treated with EGFR small interfering RNA and with the EGFR tyrosine kinase inhibitor erlotinib. The role of EGFR in IBC cell proliferation, motility, invasiveness, and change of the expression levels of epithelial-mesenchymal transition markers was examined. The role of extracellular signal–regulated kinase (ERK)-1/2 in erlotinib activity was also studied. The activity of erlotinib in tumor growth and metastasis was examined in an orthotopic xenograft model of IBC.

Erlotinib inhibited proliferation and anchorage-independent growth of IBC cells, and this inhibition was ERK dependent. Erlotinib inhibited cell motility and invasiveness and reversed the mesenchymal phenotype of IBC cells to epithelial phenotype in three-dimensional culture. Erlotinib dramatically inhibited IBC tumor growth in a xenograft model. Interestingly, erlotinib inhibited spontaneous lung metastasis, even at a low dose that had no significant effect on primary tumor growth. These erlotinib-treated tumors were converted to epithelial phenotype from mesenchymal phenotype.

The authors published results in the Clinical Cancer Research Online First on 13 October 2009. They concluded that the EGFR pathway is involved in tumor growth and metastasis of IBC. Targeting EGFR through the ERK pathway may represent an effective therapeutic approach to suppress tumorigenicity and prevent metastasis in EGFR-expressing IBC.

The study was supported by NIH grant R01 CA123318-01A1, Morgan Welch Inflammatory Breast Cancer Research Program, State of Texas Rare and Aggressive Breast Cancer Research Program, and Susan G. Komen Postdoctoral Fellowship grant.

A NEW ANTI-CD20 ANTIBODY APPROVED FOR CLL

October 28, 2009 — The US Food and Drug Administration (FDA) has granted accelerated approval of ofatumumab intravenous infusion (Arzerra, GlaxoSmithKline) for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab.

"The approval of Arzerra illustrates FDA's commitment to using the accelerated approval process to approve drugs for patients who have limited therapeutic options," said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in an agency news release. Approximately 16,000 patients are diagnosed and about 4400 die from CLL each year.

Ofatumumab is a cytolytic monoclonal antibody that binds specifically to the CD20 molecule expressed on the surface of normal and malignant B lymphocytes, making them more susceptible to immune system attack.

The approval of the drug was based primarily on data from a single-arm, multicenter study of 154 patients, of whom 93% had received prior treatment with alkylating agents and 59% had received rituximab therapy; all had received fludarabine and alemtuzumab.

Results demonstrated that treatment with ofatumumab yielded an investigator-determined overall response rate of 42% (99% confidence interval [CI], 26 – 60), with a median duration of response of 6.5 months (95% CI, 5.8 – 8.3); no complete responses were observed.

Although there are currently no data demonstrating an improvement in disease-related symptoms or increased survival, ongoing clinical studies are expected to confirm that the addition of ofatumumab to standard chemotherapy delays CLL progression.

The recommended regimen for ofatumumab consists of a 12-dose cycle: a 300-mg initial dose followed 1 week later by 2000 mg weekly for 7 doses, which is then followed 4 weeks later by 2000 mg given every 4 weeks for 4 doses. Patients should be premedicated with an intravenous corticosteroid, oral analgesic, and oral or intravenous antihistamine to reduce the risk for infusion reactions. In the study, 88% of patients received at least 8 infusions, and 54% were able to tolerate all 12.

Adverse reactions reported in 10% or more of patients receiving ofatumumab therapy include neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections.

Prolonged (≥1 week) severe neutropenia and thrombocytopenia can occur during treatment with ofatumumab, and complete blood and platelet counts should be monitored regularly.

As with other monoclonal antibodies, ofatumumab is linked to a risk for potentially fatal progressive multifocal leukoencephalopathy, which should be considered in patients who present with new onset or changes in preexisting neurologic signs and symptoms.

Ofatumumab may also cause hepatitis B virus reactivation, and high-risk patients should be screened for infection before initiation of therapy. Hepatitis B virus carriers should be closely monitored for signs of active infection during treatment and for 6 to 12 months after discontinuation of therapy.

DCIS AND RADIOTHERAPY

October 27, 2009 — Women with low- to intermediate-grade ductal carcinoma in situ (DCIS) with margins 3 mm or wider had an "acceptably low rate" of ipsilateral breast events 5 years after excision without irradiation, according to the results of a new study published online October 13 in the Journal of Clinical Oncology.

It is the first multi-institutional prospective study to examine foregoing radiation therapy (RT) in DCIS patients.

However, because longer-term follow-up is needed, the results do not mean that radiation should be skipped; therefore, the results are not practice-changing, says an editorial that accompanies the study.

The editorialists, Jay R. Harris, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, and Monica Morrow, MD, from Memorial Sloan–Kettering Cancer Center in New York City, also believe that the results might not be generalizable to the majority of women with DCIS because of the select nature of the patients involved.

Furthermore, given that fact that patients with DCIS are increasingly choosing bilateral mastectomy as their treatment, the "major clinical dilemma in DCIS today" is probably not choosing between local excision with or without radiation, suggest the editorialists. Instead, the bigger challenge might be trying to improve patients' understanding of the risks and benefits of therapies for "a disease that has almost no risk of mortality," they write.

In the new study, the 5-year rate of ipsilateral breast events in 565 patients with low- or intermediate-grade DCIS was 6.1% (95% confidence interval [CI], 4.1% to 8.2%). This prospectively determined local failure rate is in keeping with the 5% to 10% rates found in retrospective studies of similar patients treated with local excision alone, note the study authors, led by Lorie L. Hughes, MD, from Emory University in Atlanta, Georgia.

However, for patients in the study with high-grade lesions, excision alone is probably an "inadequate treatment," write Dr. Hughes and her colleagues from 8 other institutions involved in the study.

The 5-year rate of ipsilateral breast events for 105 patients with high-grade DCIS was "much higher" (15.3%; 95% CI, 8.2% to 22.5%).

The study authors also note that the overall survival was "excellent" for all of the participants in the study, and that none of the small number of deaths was related to breast cancer.

Take a Good Look at the Patients

In their editorial, Drs. Harris and Morrow question the generalizability of the results, saying that the "entered patients were generally older than the usual median age of diagnosis of DCIS, had lesions smaller than 1 cm, had margins greater than 5 mm."

Dr. Hughes and her colleagues also called attention to their patients' characteristics, noting that "patients entered in this trial had a more favorable median lesion size and width of margins than the entry criteria required."

These favorable characteristics were further delineated by the editorialists, who note that "median lesion size for this group was only 6 mm (rather than the 25 mm allowed by the protocol), and only approximately a quarter of entered patients had lesions 10 mm or larger."

About margins, the editorialists note that "approximately two thirds of patients had margins greater than 5 mm, and approximately half of patients had margins greater than 10 mm (rather than the 3 mm allowed by the protocol)."

Finally, only 9% were younger than 45 years, the editorialists highlight.

Dr. Hughes and colleagues seemed to have anticipated criticisms about their patients' characteristics. In the paper's conclusions and in its discussion section, they specify that the results in low- or intermediate-risk DCIS applied to "rigorously evaluated and selected patients."

Despite suggesting that the participating patients are not typical and emphasizing the relatively wide median margin width and relatively small median lesion size, the editorialists go on to say that excision and lesion size are not of ultimate importance in DCIS outcomes.

For the low- to intermediate-grade group, there was no significant difference in the 5-year rate of local recurrence based on margins greater or less than 10 mm (6.7% and 5.6%, respectively), and lesion size was also not a predictor of local recurrence, they write.

"Taken together, these observations indicate that the long-cherished concept that widely excised, small, low-grade DCIS lesions are least likely to recur is an overly simplistic notion," they continue.

The editorialists note that the "underlying biology of the disease, rather than the mechanics of the excision, will be the primary determinant of outcome."

"The challenge for the future is to identify markers that reliably predict behavior," they write.

What About Other Trials That Showed That RT Helped?

In their editorial, Drs. Harris and Morrow point out that the study is not a randomized controlled trial and wonder if local excision plus RT might have been better than excision alone.

"Because the study is not a randomized clinical trial, what it cannot tell us is what the reduction in the incidence of local recurrence in this highly favorable group of patients would be with the addition of RT," they write.

They note that 4 randomized trials have shown a reduction of approximately 50% in local recurrence when RT is added to excision.

"So why is the use of RT in DCIS controversial?" ask the editorialists.

The answer is found, foremost, in the lack of survival benefit. "None of the individual trials of breast-conserving surgery with and without RT showed a survival benefit for breast irradiation," they note.

However, they also note that invasive breast cancer offers a "cautionary tale" in this regard. It took 15 years of follow-up in multiple randomized clinical trials to show that local recurrence affected overall survival, observe the editorialists.

The authors and editorialists have disclosed no relevant financial relationships.

J Clin Oncol. Published online October 13, 2009. Abstract, Abstra

"LUMPECTOMY" FOR PROSTATE CANCER?

October 23, 2009 — A new finding has given fresh impetuous to the idea of focal therapy for prostate cancer, which focuses ablation on the index malignant lesion, not — as is the current standard — the whole gland.

The subject is discussed in a paper on the clinical implications of basic research in the October 22 issue of the New England Journal of Medicine.

"There is a lot of interest in this focal approach to treatment, because it reduces side effects," says author Hashim Uddin Ahmed, MRCS, BM, BCh, from University College Hospital in London, United Kingdom.

"It is based on the idea that management of localized prostate cancer can follow the organ preservation approach taken in the treatment of almost all other solid tumors," he writes. "In other words, ablation of only the malignant areas within the prostate, along with a margin of normal tissue, and preservation of normal prostate and surrounding structures will help reduce side effects."

Although the data are early, the focal approach appears to be comparable to the standard radical approach in terms of cancer control, and it greatly reduces the risk for "collateral damage" to tissues surrounding the prostate gland, Dr. Ahmed told Medscape Oncology in an interview.

The radical approach of ablating the whole prostate — with surgery, radiation, or cryotherapy — carries with it about a 70% risk for impotence and a 10% risk for incontinence, Dr. Ahmed pointed out.

Four trials have now been carried out in the United States with a focal approach, using cryotherapy, and the retrospective data from these suggest a 20% risk for impotence and risk for incontinence of less than 5% — in some series, no cases of incontinence were reported.

Both approaches show a cancer control of around 80% to 90%, he noted.

Data for the focal approach are still short term, with a follow-up of around 2 to 4 years after the procedure, whereas the radical approaches have been in use for much longer, so there are far more data; results for surgery go out 20 to 30 years. Also, because prostate cancer tends to progress slowly, it can take years before there is a relapse, so cancer control is measured by biopsies (with negative biopsies suggesting no cancer present) and biochemically (by prostate-specific antigen [PSA] screening), he added.

But the data so far suggest that the focal approach to prostate cancer therapy looks "very encouraging," Dr. Ahmed noted.

"It's like the difference between a mastectomy and a lumpectomy in breast cancer," he continued. "In prostate cancer, we are about 20 years behind, but the focal approach has been made possible only in the past few years; it's only now that we have the technology that can pinpoint lesions with millimeter accuracy."

Now that such technology is available, there is a growing interest in this focal approach to therapy, he said: "This is taking prostate cancer clinical researchers by storm."

Dr. Ahmed previously discussed the focal approach to therapy for prostate cancer in Nature Clinical Practice Oncology (2007;4:632-642).

The new finding that caused him to revisit the idea was published recently in Nature Medicine (2009;15:559-565). That study, conducted by Wennuan Liu, PhD, from Wake Forest University of Medicine, in Winston-Salem, North Carolina, and colleagues, under the leadership of Steve Bova, MD, from Johns Hopkins University, in Baltimore, Maryland, suggests that a single precursor cell is responsible for generating metastatic disease.

Those researchers analyzed tissue samples taken from men with prostate cancer who had died of disseminated disease and who had donated their bodies to science.

The team obtained 94 samples of malignant tissue from various metastatic sites taken from 30 men, and analyzed them with a high-resolution genome-wide survey of single-nucleotide and copy-number polymorphisms. They found that within each patient, metastases at various anatomically distinct sites originated from a single precursor cell.

"All of the metastases came from a single cancer cell in the prostate," Dr. Ahmed explained.

Unfortunately, Dr. Ahmed notes, the researchers were unable to determine where this single precursor cell came from, and if it was situated in the index lesion. These men had died from disseminated disease, and had undergone many different treatments for the prostate cancer, including androgen-deprivation therapy, which shrinks the gland and causes morphologic and histologic changes, he explained.

It is highly likely that this single precursor cell is found in the index lesion, Dr. Ahmed explained. There is accumulating evidence, including some new research from the Memorial Sloan-Kettering Center in New York City, which shows that the majority of aggressive cancer cells (more than 90%) are located in the index lesion. This is usually an aggressive high-grade tumor with a tendency to extend into the capsule, he said.

In contrast, there might be other "spots" of cancer within the prostate gland that are low grade. More than half of all men who are older than 60 years of age have these small low-grade tumors in their prostate, which might never grow to a point where they threaten health, he pointed out, so "it makes sense that small lesions don't need to be treated."

Focal therapy focuses on ablating just the index lesion, leaving the low-grade tumor spots and the rest of the prostate gland intact. At University College Hospital, Dr. Ahmed is involved in a clinical trial program, headed by Mark Emberton, FRCS, which is investigating focal therapy with high-intensity focused ultrasound. This is used to ablate the index lesion, and the men are followed closely with active surveillance and PSA tests every 3 months. A similar trial is ongoing at the University of Texas MD Anderson Cancer Center in Houston, but there, ablation of the index lesion is carried out with cryosurgery.

Currently, the main aim of focal therapy is to reduce the adverse effects of treatment, Dr. Ahmed said. But the hope is that by focusing on the index lesion, this approach will destroy the aggressive clone that goes on to metastasize and ultimately kill the patient, he added.

Dr. Ahmed has disclosed no relevant financial relationships.

N Engl J Med. 2009;361:1704-1706. Abstract

DOUBLING OF RISK FOR BLEEDING WITH SORAFENIB AND SUNITINIB

October 27, 2009 — Treatment of cancer patients with the targeted agents sorafenib (Nexavar, Bayer and Onyx) and sunitinib (Sutent, Pfizer) is associated with a significant increase in the risk for bleeding, a new meta-analysis concludes.

The risk for bleeding was doubled by the use of these agents, the authors report in the October issue of Lancet Oncology.

Bleeding is already mentioned as a warning in the labeling of both products, but the findings from this meta-analysis — which consisted of 6779 patients — go "beyond the label," said senior author Toni Choueiri, MD, from the Dana-Farber Cancer Institute, Harvard Medical School, in Boston, Massachusetts. The quantification of risk is new, and so is the finding that the risk is statistically significant, he told Medscape Oncology.

"Clinicians should be aware of the possibility of increased bleeding, especially in patients at high risk," the authors note.

"The risk of bleeding might be higher and more relevant in the older and frailer population, in whom even a grade 2 bleed is of clinical importance," they note. Also, the risk for bleeding might be increased in patients who are receiving chemotherapy, because this leads to bone marrow suppression and thrombocytopenia, and by the concurrent use of anticoagulant (e.g., warfarin) or antiplatelet (e.g., aspirin, clopidogrel, ticlopidine) treatment.

Currently, clinicians are "barely aware" of the risk for bleeding with these drugs, Dr. Choueiri said. It might be necessary to stop certain therapies before using these agents, or to proceed with caution in patients who are taking concomitant medication, he added.

Consequence of Their Mode of Action

Sorafenib and sunitinib both act as inhibitors of vascular endothelial growth-factor (VEGF) tyrosine kinase, and both were originally approved for use in advanced renal cell carcinoma. Sorafenib is also approved for use in hepatocellular carcinoma, and sunitinib has an additional indication for gastrointestinal stromal tumors. Both drugs are being tested in a variety of other cancers, and so "an increase in their use is expected in the near future," the authors note.

"Recognition of patterns of toxic effects and understanding the mechanism of action of these drugs is important so that early and adequate intervention or prevention can be done," they write.

An increased risk for bleeding has been reported for another drug that inhibits VEGF — bevacizumab (Avastin) — but by a different mechanism. Bevacizumab is a humanized monoclonal antibody directed against serum VEGF ligand, the authors note.

VEGF is important for the survival of endothelial cells and helps to maintain the architecture and integrity of the microvasculature, the authors explain. If VEGF is blocked, the repair and renewal capacity of endothelial cells in response to trauma could be altered, increasing the risk for hemorrhage.

Doubling in Risk for All Grades of Bleeding Events

The meta-analysis — which the authors believe is the first on this issue — included 23 clinical trials. The calculation of relative risk involved 1325 patients receiving VEGF receptor inhibitors (748 receiving sorafenib and 577 receiving sunitinib), and 1215 patients in the control group receiving placebo.

The relative risk for all grades of bleeding events associated with sorafenib and sunitinib (for randomized clinical trials only) was 2.0 (1.14–3.49; P = .015).

"The overall incidence of risk of all-grade bleeding events was 16.7%, with no difference recorded between sorafenib or sunitinib or type of malignant disease," the authors report.

However, a further analysis suggested that among patients treated with sorafenib, the incidence of all-grade bleeding was higher in those with renal cell carcinoma than with other tumors.

The risk for high-grade bleeding events was not significantly higher; the overall incidence was 2.4%, the authors report. The most important of these seemed to be grade 5 cerebral and pulmonary hemorrhages.

Dr. Choueiri and colleagues suggest several explanations for the fact that the risk for high-grade bleeding events was raised only slightly, including the small number of these events and the differences in the way that bleeding events were graded by the trials.

The incidence of high-grade bleeding events for sorafenib and sunitinib (2.4%) is similar to that reported for bevacizumab (2.7%) in a meta-analysis presented earlier this year at the American Society of Clinical Oncology 45th Annual Meeting (Abstract 9584). In that case, this increase in risk for high-grade bleeding events was significant, the authors note, as was the increase in the risk for all grades of bleeding events (36.3%). However, they add, in another meta-analysis of bevacizumab (in which only industry-sponsored trials were selected), the risk for bleeding was slightly higher than that in the control group (hazard ratio, 1.69; P = .09) and was not significantly increased (J Natl Cancer Inst. 2007;99:1232-1239).

The risks for bleeding with bevacizumab are not well quantified, and this adverse effect is not well known, in contrast to some of the other adverse effects seen with this agent, such as thromboembolism, hypertension, bowel perforation, and proteinuria, Dr. Choueiri noted.

BRCA1 AND DEPLETION OF OOCYTE RESERVE

October 26, 2009 (Atlanta, Georgia) — BRCA1 gene mutations appear to be associated with early depletion of oocyte reserve, supporting the link between breast and ovarian cancer risk and infertility.

Kutluk Oktay, MD, from the Department of Obstetrics & Gynecology at the Westchester Medical Center-New York Medical College in Valhalla, presented the findings here at the American Society for Reproductive Medicine 65th Annual Meeting.

According to the researchers, murine models suggest a relation between DNA repair gene function and germ cell reserve. Their study sought to determine a link between deleterious mutations in BRCA genes and diminished oocyte reserve, as assessed by response to ovarian stimulation.

Dr. Oktay and colleagues analyzed previous data from 82 women with breast cancer who underwent oocyte/embryo freezing. Patients younger than 38 years with normal baseline ovarian reserve received 5 mg/day of letrozole and 150 to 300 IU/day of follicle stimulating hormone (FSH) prior to chemotherapy.

Of the 82 women, 57% were tested for BRCA mutations. Of those tested, 14 (30%) did have a BRCA mutation (9 had a BRCA1 mutation, 4 had a BRCA2 mutation, and 1 had both BRCA1 and BRCA2 mutations).

Poor ovarian response rate was significantly higher in patients with a BRCA1 and/or 2 mutation (33.3%) than in those who did not have the mutation (3.3%; P = .014) and in BRCA untested women (2.9%; P = .012). All poor responders were BRCA1-positive, and none had only a BRCA2 mutation.

After controlling for age, FSH level, and body mass index, the researchers found a significantly increased risk for poor response in women who were BRCA-positive, compared with those who were BRCA-negative, with an odds ratio of 28.7 (95% confidence interval, 1.8 - 447.0; P =.016).

BRCA-positive women also tended to have lower oocyte numbers (P = .025), and BRCA1 but not BRCA2 mutations were associated with poor response (P = .001).

According to Dr. Oktay, BRCA mutations are found in 1 in 1000 females in the general population and in up to 2.5% of Jewish-Ashkenazi patients. "Poor response to in vitro fertilization with a family history of breast and/or ovarian cancer should raise the flag that a BRCA mutation might be involved," he told Medscape Ob/Gyn & Women's Health.

"The finding that oocyte numbers may be diminished with BRCA mutations is not surprising, since BRCA is a DNA repair gene and oocytes may not survive if that mechanism is deficient," he said. "We need to do basic research studies to determine the mechanism by which BRCA mutations result in diminished egg reserve, as well as a larger clinical study," he added.

"These findings are very novel," said Dr. Keefe, chair of the Department of Obstetrics and Gynecology at the NYU Langone Medical Center in New York CIty, "but based on what we now know from this work, women with BRCA mutations should be advised that they may lose their eggs earlier than women of the same age without BRCA mutations," he told Medscape Ob/Gyn & Women's Health.

Dr. Keefe also noted that women with BRCA mutations considering preimplantation genetic diagnosis (PGD) should be aware that they might not have as many eggs and embryos to test as women of their same age undergoing PGD for other indications.

According to Dr. Keefe, most egg problems may eventually be linked to one or another specific genetic change, just like fever has been linked to specific bacteria.

This study was supported by a National Institutes of Health grant. Dr. Oktay and Dr. Keefe have disclosed no relevant financial relationships..

American Society for Reproductive Medicine (ASRM) 65th Annual Meeting: Abstract O-103. Presented October 21, 2009.

RITUXIMAB FOR ANCA+ VASCULITIS

October 23, 2009 (Philadelphia, Pennsylvania) — Rituximab is as effective as cyclophosphamide for the treatment of vasculitis and superior to cyclophosphamide for patients experiencing a severe disease flare, according to results of a randomized controlled trial, called RAVE, presented here at American College of Rheumatology 2009.

Cyclophosphamide has been the standard of care for reduction remission for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for many decades, but it is associated with serious toxicities, including neutropenia, infections, genitourinary malignancies, and infertility.

RAVE was a multicenter randomized double-blind placebo-controlled trial comparing rituximab (375 mg/m² intravenous weekly for 4 weeks) with cyclophosphamide (2 mg/kg per day orally). The study met its primary end point of noninferiority, showing that rituximab is as effective as cyclophosphamide.

Although rituximab was not superior to cyclophosphamide in the overall study population, it was superior for the induction of remission in ANCA-associated vasculitis for patients who entered the trial with a severe disease flare, explained Ulrich Specks, MD, from the Mayo Clinic in Rochester, Minnesota, for severe ANCA-associated vasculitis.

"Rituximab is the first proven alternative to cyclophosphamide in severe ANCA-associated vasculitis, and it is effective and well tolerated. This is particularly relevant for patients with severe disease and those of child-bearing age," Dr. Specks stated.

ANCA vasculitis is a systemic autoimmune disease caused by an overreaction of the immune system to many organs of the body. Wegener's granulomatosis, microscopic polyangiitis, and Churg–Strauss syndrome are variants of ANCA-associated vasculitis.

The study assigned 99 patients to rituximab and 98 to cyclophosphamide, with the goal of obtaining complete remission and withdrawing patients from prednisone. Three quarters of the group had Wegener's granulomatosis and one quarter had microscopic polyangiitis.

Disease remission was reported in 63.6% of the rituximab group and 53.1% of the cyclophosphamide group. A reduction in disease activity, measured by a score of 0 on the Birmingham Vasculitis Activity Score for Wegener's granulomatosis, and tapering of prednisone to less than 10 mg/day was observed in 70.7% of the rituximab group and 62.2% of the cyclophosphamide group.

Rituximab obtained almost complete depletion of B-cells, which is thought to be important in controlling this disease. Cyclophosphamide also depleted B-cells, but the effect was less robust, Dr. Specks said.

The difference between the 2 treatment groups was not significant in the newly diagnosed patients (n = 96), but rituximab was superior in achieving complete remission in the 101 patients with severe disease flares at baseline (66.7% vs 42%, representing almost a 25% absolute improvement).

The rate of protocol-defined adverse events was similar between groups (0.06% for rituximab and 0.08% for cyclophosphamide), with no difference in rate of infection. Fewer patients treated with rituximab experienced 1 or more adverse event(s), compared with cyclophosphamide (19.2% vs 32.7; P = .03).

"Strong and Exciting" Data

"These data are strong and exciting," said Robert Terkeltaub, MD, from the VA Medical Center, University of California, San Diego.

"This is good news because oral cyclophosphamide is associated with toxicities that include genitourinary malignancies, loss of fertility, and infection. Many patients have difficulty tolerating long-term cyclophosphamide treatment for ANCA-associated vasculitis. Studies in this patient group have shown that after 10 to 15 years of treatment, the incidence of [genitourinary] transitional cell carcinoma was 10% to 15%, which is startlingly high and unacceptable," Dr. Terkeltaub stated.

He commended the RAVE investigators for a well-designed study. "It's great to know that this alternative therapy works as well, with more rapid B-cell depletion, as cyclophosphamide," he continued. Another plus is that rituximab is already used to treat rheumatoid arthritis, and rheumatologists are comfortable using it.

In Dr. Terkeltaub's opinion, "RAVE showed that rituximab is a significant therapeutic advance in ANCA-associated vasculitis."

Medications were provided by Genentech and Biogenic Idec, and the study received support from the Immune Tolerance Network. Dr. Specks has disclosed no relevant financial relationships. Dr. Terkeltaub reports being a consultant for URL Pharma, Regeneron, Novartis, Takeda, Savient, and Ardea.

American College of Rheumatology (ACR) 2009: Abstract 550. Presented October 18, 2009.

GLEEVEC FOR SCLERODERMA

October 23, 2009 (Philadelphia, Pennsylvania) — Imatinib (Gleevec), a drug that has significantly improved survival in chronic myelogenous leukemia and gastrointestinal stromal tumor, is showing beneficial effects on skin and lung manifestations in patients with diffuse cutaneous scleroderma. Interim results of a preliminary trial were reported here at American College of Rheumatology (ACR) 2009.

Imatinib was tolerable for most patients with dose adjustments and management of adverse effects, researchers announced.

These promising preliminary results in scleroderma need to be replicated in a phase 3 randomized controlled trial of longer duration, said lead author Jessica Gordon, MD, from the Hospital for Special Surgery in New York City.

The phase 2a single-center single-group open-label clinical trial involved 30 patients with diffuse scleroderma; 20 had the disease for less than 4 years and 10 had it for 4 years or more. Imatinib 400 mg/day was given for 12 months, and patients were evaluated 15 months after the initiation of treatment. About one quarter of the patients had received no previous therapy; the other three quarters were taking multiple antirheumatic drugs. Mean age was 48.4 years, 80% were women, 74% were Caucasian, 13% were African American, and 13% were Hispanic.

Efficacy data were available at 3 and 6 months for 26 patients, at 9 months for 21 patients, and at 12 months for 17 patients. Safety data were available for all patients who took at least 1 dose of the study drug.

Of the 340 adverse events reported, 177 were possibly related to imatinib. Thirty six infections occurred, and 7 required hospitalization. There were 24 serious adverse events — 1 possibly related to imatinib and 14 occurring in 1 patient who dropped out of the study. That patient had received multiple antirheumatic drugs prior to imatinib, Dr. Gordon noted. Edema occurred in 80% of patients, nausea in 73%, myalgia in 63%, and fatigue in 37%.

Eighty-three percent of patients required dose adjustments for muscle-related problems (37%), fluid retention (30%), fatigue (13%), and nausea (13%). The median dose of imatinib was 350 mg.

At 12 months, in 17 evaluable patients, the mean improvement in Modified Rodnan Skin Score (MRSS) was 7.1 points, reflecting a reduction in skin thickening. The change in average MRSS became more pronounced over time. Skin biopsy showed reduced sclerosis and increased interstitial space.

Pulmonary function tests showed a 7.8% improvement in forced vital capacity after 12 months of treatment and an 8.8% improvement in diffusion capacity.

"Imatinib stabilized pulmonary parameters in patients with and without interstitial lung disease," Dr. Gordon said.

A smaller proof-of-concept study of 10 patients with active diffuse scleroderma was also reported at ACR 2009. That study failed to show improvement in skin thickening with imatinib and found that patients had difficulty tolerating the drug. Lead author Janet Pope, MD, from St. Joseph's Health Care in London, Ontario, said imatinib was unlikely to be a feasible treatment for early active diffuse scleroderma.

What to Make of Conflicting Results

A scleroderma specialist put these 2 preliminary studies into perspective for Medscape Rheumatology. Monique Hinchcliff, MD, from the Scleroderma Program at Northwestern University School of Medicine in Chicago, Illinois, said: "The effect on skin thickening reported by Gordon et al. is an important finding. Pope et al. found that imatinib 600 mg/day was not well tolerated in patients with diffuse scleroderma and that there was no reduction in skin thickening in patients taking the drug.

Despite these findings, patient- and physician-reported outcomes were the same or improved in 6 patients in the second study. "Some patients felt better on the drug despite the side effects and lack of skin improvement," she explained.

"The take-home message from these preliminary studies is that imatinib may be a drug for some people with scleroderma — probably a subset of patients, perhaps with early disease. We need to identify subgroups prospectively that are imatinib responders. Also, we need a bigger study with proper controls powered to show a significant difference between groups," she stated.

Dr. Gordon, Dr. Pope, and Dr. Hinchcliff have disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2009: Abstract 606 and 608. Presented October 18, 2009.

TRADITIONAL THERAPY FOR RHEUMATOID ARTHRITIS

Traditional Therapy as Effective as Newer Biologics in Early Rheumatoid Arthritis

Alice Goodman

October 27, 2009 (Philadelphia, Pennsylvania) — Three older disease-modifying anti-rheumatic drugs (DMARDs) were as effective as the biologic agent etanercept (Enbrel) plus methotrexate in patients with early rheumatoid arthritis (RA). Researchers said they were surprised by the results of the 2-year Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial, which were announced here at American College of Rheumatology (ACR) 2009.

"Most rheumatologists would have predicted that the biologic therapy [anti-tumor necrosis factor agent] would be better. We still need to see the x-ray results, which will be available in 2010, to see if either treatment [approach] is better," said Larry Moreland, MD, from the University of Pittsburgh in Pennsylvania.

Although these findings raise questions about the value of more expensive therapy with new biologic agents for an overall population of RA patients, Dr. Moreland said that biologic therapy might be better for specific subsets of patients, but exactly which subsets will have preferential benefit is currently unknown.

Investigators with the TEAR trial enrolled 755 patients with early aggressive RA (mean duration from diagnosis, 3.6 months), limited exposure to DMARDs (less than 2 months), and treatment-naïve to biologics used to treat RA. A total of 48% had previous exposure to oral prednisone (≤10 mg/day). The majority were females (72%), and 79.6% were Caucasian. Mean age was 49 years.

The study had 4 treatment groups. Two groups were initiated on drug therapy at the start of the study: 1 group with a triple-drug combination of older drugs (methotrexate, sulfasalazine, and hydroxychloroquine) and 1 group with methotrexate plus the anti-tumor necrosis factor agent etanercept. Two other groups were treated initially with methotrexate and then, at 6 months, if they had evidence of persistent disease activity, they were assigned to either the traditional 3-drug combination or to methotrexate plus etanercept (step-up therapy).

Dr. Moreland and colleagues presented 6-month Disease Activity Score (DAS) 28 findings. No difference between the 2 treatments was observed, either in the immediate-therapy groups or the step-up therapy groups. At 2 years, DAS 28 scores were 3.1 for triple therapy and 3.0 for methotrexate/etanercept in the immediate-therapy groups; for step-up therapy, DAS 28 was 2.8 for both groups.

Patients in both immediate-therapy groups improved more quickly than those in the step-up therapy groups. At 6 months, a much higher percentage of the immediate-therapy groups were improved, according to ACR20, ACR50, and ACR70 (instruments showing 20%, 50%, and 70% improvement, respectively, on the ACR measure). "This study provides exciting news that, for a significant number of patients, the 3-drug combination is as effective as biologic agents," stated Eric Matteson, MD, from the Mayo Clinic in Rochester, Minnesota. "It is compelling that we can do as well in a group of patients with these older drugs."

He also said that the x-ray data will be important. "It is intuitive that x-ray damage follows disease activity. We will know those results down the road."

Biologics might not work in individual patients, and DMARDs might not work in individual patients, he continued. "We are just starting to understand which patients don't respond well to these agents. We hope to be able to tease out these factors and to define which drugs are best in specific subsets of patients."

"This study showed that biologics are not the right approach for every patient, and this has cost implications," he said.

The study was supported by Immunex and Amgen. Dr. Moreland reports having financial ties with Amgen, Barr, Pharmacia, and NIAMS-NIH. Dr. Matteson reports having financial ties with Amgen, Wyeth, UCB, Genentech, and Pfizer.

American College of Rheumatology (ACR) 2009: Abstract 1895. Presented October 20, 2009.

NEW TREATMENT FOR LUPUS

October 26, 2009 (Philadelphia, Pennsylvania) — Positive 1-year results from the BLISS-52 study show that belimumab (Benlysta) achieved clinically meaningful improvements and was safe in patients with systemic lupus erythematosus (SLE). "Belimumab represents the first new treatment for SLE in decades," said Sandra Navarra, MD, from the University of Santo Tomas Hospital in Manila, Philippines, who presented results here at a late-breaking session of American College of Rheumatology (ACR) 2009.

It has been more than 50 years since the US Food and Drug Administration (FDA) has approved a new medication for lupus. Belimumab inhibits the B-lymphocyte stimulator and presumably reduces autoantibody levels in SLE.

Belimumab significantly reduced disease activity, disease flares, and use of steroids, and improved fatigue and quality of life, compared with placebo. BLISS-52 is the first of 2 pivotal phase 3 trials in SLE. If results of the second phase 3 trial (BLISS-76) are positive when released in November 2009, the drug will be submitted for FDA approval in the first half of 2010.

The double-blind placebo-controlled BLISS-52 study involved 865 patients with active SLE who were randomized to 1 of 3 groups: placebo (n = 286), belimumab 1 mg/kg (n = 288), or belimumab 10/mg/kg (n = 290). Patients in all 3 groups also received standard of care, including prednisone (96%) and immunosuppressants (42%). Baseline demographic and disease characteristics were similar in the 3 groups. Average age was about 35 years, 95% of the study population was female, and Asians comprised 36% of the population.

At week 52, belimumab achieved a clinically and statistically significant improvement in the primary composite end point, called the SLE Responder Index (SRI) (a 4-point improvement on the SELENA SLE Disease Activity Index [SLEDAI], plus no new British Isles Lupus Assessment Group [BILAG] 1A or 2B flares, plus no worsening on Physician Global Assessment [PGA]).

Both doses of belimumab achieved a significant improvement on SRI, compared with placebo; response rates were 57.6% for belimumab 10 mg/kg plus standard of care; 51.4% for belimumab 1 mg/kg plus standard of care; and 43.6% for placebo plus standard of care (P = .0006 and P = .013 for the 10 and 1 mg/kg doses, respectively).

Improvement was sustained for both doses of belimumab from week 24 and week 28, respectively, through week 52 (P < .05 for both treatment groups compared with placebo). The improvement was consistent across subgroups and ethnicities, Dr. Navarra said. A dose-response trend was seen, with more responses in the higher-dose group.

Time to severe flares and moderate flares was delayed with belimumab. Median time to first SLE flare was 119 days for belimumab 10 mg/kg, 126 days for belimumab 1 mg/kg, and 84 days for placebo (P = .0036 and P = .0026 for the 2 doses, respectively, vs placebo). The risk of having a severe flare was reduced by 43% and 24% in the 2 groups, respectively (P = .0055 and P = .01342, respectively, vs placebo). The risk of experiencing a severe flare (BILAG A) or more than 1 moderate flare (BILAG B) was reduced by 42% and 13% in the 2 treatment groups, respectively (P = .0016 and P = .3722, respectively, vs placebo).

Belimumab 10 mg/kg significantly improved PGA at week 52 (P = .0003), and both doses improved quality of life results as reflected by the SF-36 Physical Component Summary (P = .02 and P = .025 for the 1 and 10 mg/kg doses, respectively, vs placebo).

Belimumab was also prednisone-sparing, with a higher percentage of patients who reduced their steroid drugs by at least 50% at week 52 (27.7% for the 10 mg/kg group, 23% for the 1 mg/kg group, and 17.7% for the placebo group).

Fatigue and quality of life were also better in the 10 mg/kg group than in the placebo group within 4 to 8 weeks of study initiation and, by week 52, both belimumab groups achieved significant improvement in health-related quality of life on the FACIT-Fatigue Scale (P < .05 for both doses vs placebo).

Belimumab was generally well tolerated, with comparable rates of adverse events, serious adverse events, infections, and deaths for all 3 groups. Serious infections occurred in 6.1% of the belimumab-treated patients and 5.9% of the placebo-treated patients. The most common adverse events included headache, arthralgia, upper respiratory tract infections, urinary tract infections, and influenza, and these were comparable between groups. No malignancies were reported.

Results Called a Major Achievement

Zahi Touma, MD, from the University of Toronto in Ontario, called this trial a major achievement. "Other trials of biologic agents for treatment of lupus have failed. Finally, we have a study that shows a drug that works, with positive results in lupus patients. This is very important. Nothing has been approved by the FDA since cyclophosphamide," he said.

Dr. Touma believes that the explanation for the failure of other drug trials is the lack of a good primary outcome measure to assess disease activity in SLE. "The BLISS-52 investigators generated a novel outcome measure — the SLE Responder Index, which is a composite measure of SLEDAI, BILAG, and quality-of-life measures. It's too early to validate this measure, but the composite end point allowed the investigators to demonstrate improvement," he said.

Dr. Touma is developing an instrument called the SRI-50, which shows at least a 50% improvement in SLE, similar to the ACR50 for rheumatoid arthritis.

The BLISS-52 study was funded by Human Genome Sciences and GlaxoSmithKline. Dr. Navarra reports financial ties with Pfizer, Merck, Roche, Wyeth, Human Genome Sciences, and Schering-Plough. Dr. Touma has disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2009: Late-Breaking Abstract 1. Presented October 20, 2009.

ΑΠΟ ΧΑΝΟΥΜΟ-BLOG ΣΧΕΤΙΚΑ ΜΕ ΤΗ ΝΤΟΥΝΤΟΥΚΑ ΤΟΥ ΜΠΑΚΑΛΟΓΑΤΟΥ

TT1981
ΠΑΙΔΙΑ ΣΤΕΙΛΤΕ Ε-ΜΑΙL ΣΤΟΝ ΑΛΦΑ ΣΤΟ pr@alphatv.gr

ΑΝ ΕΙΝΑΙ ΔΥΝΑΤΟΝ ΜΕ ΤΟΝ ΚΑΡΑΓΙΟΖΗ ΤΟ SPEAKER!!!!
mixalis rodos 2009
BARCA o Gayros,xa xa xa xa xa xa xa xa xa.
Braveheart
Φτού σας ρε... που χαίρεστε επειδή αποκλείστηκε ο θρύλος.

Με τι θα γελάμε αύριο ε;

Τώρα που οι έμμισθοι κονδυλοφόροι δεν θα μπορούν να εκθειάζουν την Καρδιά του Πρωταθλητή....

Γιατί θα γράφουν τώρα ε;

Για τη νεφραμιά του Πρωταθλητή;

Είναι αστείο αυτό ε;
aisxos
einai ntropi gia ton alpha na vazei tetoious sportcaster na metadidoun ton agona..o anthropos prepei na einai vammenos osfp kai to kako einai pos den krataei oute kan ta prosximata....
βαγγος αεκαρα
ρε παιδια ελεος πια με αυτους τους εκφωνητες! αυτος ο παπαρας στον ΑΛΦΑ μολις εφαγε το γκολ ο γαυρος,εκανε σαν Μ.Παρασκευη! και μολις κανει καμια ευκαιρια ο Διορισμενος,ενθουσιαζεται λες και εχει καμια γκομενα διπλα του και τον...γαργαλαει!!! ασε που ολα τα φαουλ τα βλεπει υπερ του γαυρου και αυτα που δεν δινει υπερ των Σερρων τα κανει γαργαρα. ουστ πια,ουστ!
Τselemba
Ρουφάτε ρε κολόγαυροι.
Τα έβαψε μαύρα ο εκψωνητής
ΓΑΤΟΣ 21
ΘΕΙΑ ΔΙΚΗ...ΟΛΑ ΕΔΩ ΠΛΗΡΩΝΟΝΤΑΙ...
βαγγος αεκαρα
πω πω ρε π****η μου δεν παιζεται ο εκφωνητης! θα βαλει τα κλαματα σε λιγο!
τηνος
μ'αρεσει!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
nickpet21
Και κλαμα τα γαυρακια
kostas giannena
xa xa xa xa kala na pathoune xa xa xa xa
adriano
ΕΝΣΤΑΣΗΗΗΗΗΗΗΗΗΗΗ
ΕΝΣΤΑΣΗΗΗΗΗΗΗΗΗΗΗ
greek1973
Καλά ρε παιδία ξέχασε ο θειος να στείλει το Δαλουκα;
showman28
Ti egine re magkes gaurakoi??? mipws o athanasiadis eixe plirwsei ton papadopoulo kai itan syke to matsaki??giati mono ama einai syke xanete... K...iolia dimosiografoi twra o gauros den mikrainei?
Mono i AEK mikrainei ama xanei???H arxi tou telous sas...Pame re Timour
anastimenos
ti klapsa einai ayti me ton ekfwniti re paidia????
lamia21
arxisame na sfyrame oti theloyme...
vale tn swthrakh na teleiwsei tn doyleia!
kostas
paei o gay-ros apo twra!!!!!ante gia sas ante gia sas ante spiti pou .....
spesialistas21
diploi einai oi agwnes?????????
ενωσις
Αν πραγματικά εκνευρίζεστε με τον εκφωνητή στείλτε e-mail στον ALPHA. Εγώ το έκανα ήδη. Χωρίς καθωσπρεπισμούς και αηδίες. Βρίστε τους χύμα, πελάτες είστε. Οταν κάτι σας χαλάει κάντε μια κίνηση...
kyriakosv
oraios o mitroglou! den itan offside?
kyriakosv
Thrile mporeis mporeis na prokritheis!!!
mpouaxaxaxaxa
τηνος
μ΄αρεσει!!!!!!!!!!!!!!!!!!!!
vagos30
TON HPIE KANONIKA O GAVROS...PAME AEKARA MOU NA PAROYME TO KYPELLO!
nickpet21
3-1
Ζητωωωωωωωωωωωωωωωωωωωωωω!!!!!!!!
popay
ΜΠΡΑΒΟ ΡΕ ΣΕΡΡΕΣ ...ΟΧΙ ΓΙΑ ΜΕΝΑ ΓΙΑ ΤΟ ΦΟΥΚΑΡΙΑΡΗ ΤΟΝ ΣΠΙΚΕΡ...ΧΑΧΑΧΑΧΑΧΑΧΧΑΑΧΑΧΑΧ
popay
ΜΠΡΑΒΟ ΡΕ ΣΕΡΡΕΣ ...ΟΧΙ ΓΙΑ ΜΕΝΑ ΓΙΑ ΤΟ ΦΟΥΚΑΡΙΑΡΗ ΤΟΝ ΣΠΙΚΕΡ...ΧΑΧΑΧΑΧΑΧΑΧΧΑΑΧΑΧΑΧ
τηνος
μ΄αρεσει!!!!!!!!!!!!!!!!!!!!
nickpet21
Την γλιτωσατε με την Καβαλα.
Την γλιτωσατε με τον Εργοτελη.
Ρουφατε τον ρε κωλογαυροι απο τις Σερρες.
cosa nostra
Το γλέντι των Σερρών!
El_Pasooo
Re milame piga na spasw to TV me ton spiker poso gavros piaaaaa poso ???

Eleoessss pia sto ALPHA den ntreponte ligo ???
Prepi na katalavoun oti den tous vlepoun mono gabri alla oloi i ellada ntropi sou kseftila spiker.

Bravo ston sfiriktra pantos pou esto kai an afise ligo to skliro peknidi meta to 70 den edose kana penalti na mas teliosi opos kanoun sinithos ...

FISA ROUFA TRAPATONEEEE SAS PIGAN REE
Avtwvns
Μπουχαχαχαχαχαχα! Καποτε επρεπε να τελειωσει η ρεντα του Ζικο!
PANOS
ΜΟΛΙΣ Η ΚΩΛΟΦΑΡΔΙΑ ΕΣΠΑΣΕ Η ΣΕΡΕΣ ΕΚΑΝΑΝ ΤΟ ΓΑΥΡΟ ΣΚΟΝΗ ΚΑΙ Ο ΔΙΑΙΤΗΤΗΣ ΣΤΟ 3-1 ΔΕΝ ΕΔΩΣΕ ΤΟ ΠΕΝΑΛΤΙ Ο ΕΠΟΠΤΗΣ ΤΟ ΕΔΩΣΕ ΟΧΑΡΑΛΑΜΠΙΔΗΣ ΕΣΠΡΩΧΝΕ ΟΣΟ ΜΠΟΡΟΥΣΕ ΑΛΛΑ Ο ΘΡΥΛΟΣ ΧΩΡΙΣ ΚΟΡΑΚΙ ΕΙΝΑΙ ΛΙΓΟΣ Η ΑΕΚΑΡΑ ΦΕΤΟΣ ΕΙΝΑΙ ΑΤΥΧΗ ΥΠΟΜΟΝΗ ΘΑ ΣΤΡΩΣΕΙ ΟΜΑΔΑ ΠΟΥ ΚΑΝΕΙ ΕΥΚΑΙΡΙΕΣ ΜΗ ΤΙ ΦΟΒΑΣΤΕ ΘΑ ΕΡΘΟΥΝ ΤΑ ΓΚΟΛ ΟΙ ΓΑΥΡΟΙ ΣΕ ΛΙΓΟ ΚΑΙΡΟ ΘΑ ΔΙΩΞΟΥΝ ΤΟ ΖΙΚΟ ΘΥΜΗΘΕΙΤΕ ΤΟ ΟΙ ΙΣΟΡΟΠΙΕΣ ΕΙΝΑΙ ΛΕΠΤΕΣ
kostas
Απο κακού ήτανε!!!!
Μια του κλέφτη δυο του κλεφτη(για να μην πω του κατσικοκλέφτη) αλλα είπαμε ! Η κολοφαρδία έχει και τα όριά της!
Αι σιχτιρ κολογαυροι παρτε να χετε τωρα.
rock21
RE GAVRAKIA MIA FORA PE3ATE ME TI DIETISIA STA ISA (SXEDON) KAI NA POU EGINE! AFTA GIA NA MA8ENETE NA MIN KANETE APATEWNIES!! ANTE NA DOUME TI 8A KANOUME K EMEIS!!
omd
Μπραβο στο διαιτητή για το αυστηρό 50-50. Κανα παιχτάκι Ελληνα απ τις Σέρρες δεν μπορούμε να παρουμε?? Τι μπαλαρα παίξανε τα παιδια ρε!!
popay
ΚΑΙ ΚΛΑΜΑΑΑΑΑ ΤΑ ΓΑΥΡΑΚΙΑ.........Κ Ο ΣΠΙΚΕΡ ΜΗΝ ΞΕΧΝΙΟΜΑΣΤΕ...ΧΑΧΑΧΧΑΧΧΑΧΑΧΧΑΧ
Alex AEK
Κύριε εκφωνητά, κυριε εκφωνητά, Μ Π Α Ν Α Ν Α !!!!!! Πολλά μπράβο στον Πανσερραικό. " Ο Ολυμπιακός με τις πολλές απουσίες" χαχαχαχαχαχα . Υπάρχει και θεός για τούς αλαζόνες..........
Kamelot21
Φέρτε να πιω να ξημερωθώ....
Christos21
Καιρός ν'αρχίσει να καταρέει το παραμύθι.... Όλο στο τέλος και με χάλια μπάλα να παίρνουμε τα παιχνιδάκια δεν γίνεται. Άντε να φάνε και το Ζίκο τώρα. Έρχονται και αναβιώνουν εποχές κορνέ.....! Όλοι ΡΕΝΤΗ να απωθεώσουμε τους νταμπλούχους!!!
Avtwvns
Κανε μας μια αναλυση τωρα ρε σπηκερ της πλακας!!!
R21

ΚΑΙΡΟΣ ΗΤΑΝ ΝΑ ΤΗΝ ΠΛΗΡΩΣΕΙ Κ ΜΙΑ ΦΟΡΑ ΤΟ ΠΤΩΜΑ ΠΟΥ ΛΕΓΕΤΑΙ ΟΣΦΠ.
dolmance
Ante geia sas ante geia sas,kai ante spiti pou plekei i mama mas
blade21
ΕΛΑ ΖΙΚΟ ΜΠΑΝΑΝΑ!!!!!!!!!!!!!!!! ΒΡΑΖΙΛΙΑΣ ΕΙΝΑΙ!
dim-aekara21
pou itan smr o ntopo-sidis oeo?????kala gia polla gelia o ekfwnitis.....re pote tha katalavoun oti paizoun sto podosfairo tou gay-rou kai oxi sto volley???????? S A P S A L W T H I K A M E REEEEEEEEEEEEEEEEEEEEEEEE!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
ΓΑΤΟΣ 21
ΚΑΙ ΤΟΥ ΧΡΟΝΟΥ,ΜΕ ΑΓΑΠΗ....
Ναξιώτης
Η ΚΑΛΥΤΕΡΗ ΟΜΑΔΑ ΚΕΡΔΙΣΕ!!!! Μπράβο στον Όγιος που είναι προπονητάρα και απέδειξε ότι το μπάτζετ δεν κάνει ομάδες από μόνο του. Που να του δίναμε και τα λεφτά του Κοτσώνη (τώρα που ο Μπάγεβιτς θα πάει στην Εθνική). Αν και Ναξιώτης, σήμερα αγαπώ τις Σέρρες! Μπράβο τους και καλές διακοπές στους διορισμένους.
mavros21
Koitaxte ti pa8an oi gayroi gi auto ksypnate min pa8oume kamia tetoia nila...twra pou o megalyteros antipalos efyge apo ti mesi einai wra na na ktypisoume to kupello.emeis k o pao meiname prepei na ftasoume teliko
Kain
ΦΦΦΦΦΦΦΦΦΦΦΦΦΦΑΑΑΑΑΑΑΑΑΠΠΠΠΠΠΠΠΠΠΠΠΠΠΠΠ
aekpanwapola
ΟΛΟΙ ΟΙ ΔΙΕΣΤΡΑΜΕΝΟΙ ΞΕΣΠΑΝΕ ΠΑΝΩ ΣΤΟ ΝΕΑΡΟ, ΤΡΥΦΕΡΟ, ΣΤΕΦΑΝΩΜΕΝΟ ΕΦΗΒΟ.
WHY?
ΘΡΥΝΟΣ
NA ΠΟΙΟΣ ΕΙΝΑΙ Ο ΟΛΥΜΠΙΑΚΟΣ...GAYROI ΡΟΥΦΙΑΝΟΙ,ΚΟΤΟΠΟΥΛΑ ΜΕ ΚΡΑΝΗ.ΟΥΣΤ ΑΠΟ ΤΟ ΚΥΠΕΛΟ...
Ναξιώτης
Η ΚΑΛΥΤΕΡΗ ΟΜΑΔΑ ΚΕΡΔΙΣΕ!!!! Μπράβο στον Όγιος που είναι προπονητάρα και απέδειξε ότι το μπάτζετ δεν κάνει ομάδες από μόνο του. Που να του δίναμε και τα λεφτά του Κοτσώνη (τώρα που ο Μπάγεβιτς θα πάει στην Εθνική). Αν και Ναξιώτης, σήμερα αγαπώ τις Σέρρες! Μπράβο τους και καλές διακοπές στους διορισμένους.
kostas 21
αντε γεια αντε γεια. το κυπελο το χασαμε παιδιααααααα, τ τσ.
R21
Κυπελλοοοοοοο κυπελλοοοοο ΑΕΚΑΡΑ ΦΕΡΕ ΜΑΣ ΤΟ ΚΥΠΕΛΛΟΟΟΟ ΚΥΠΕΛΛΟΟΟΟ ΚΥΠΕΛΟΟΟ ΓΙΑ ΤΟΝ ΔΙΚΕΦΑΛΟΟΟΟΟ !
xokan
να ποιος ειναι ο ολυμπιακοςςςςςςς χαχαχαχαχαχα
ΠΡΟΒΟΚΑΤΟΡΑΣ!!!
ΑΠΟ ΔΙΑΣΤΡΟΦΗ ΚΑΙ ΜΟΝΟ ΕΙΔΑ ΤΟ ΠΑΙΧΝΙΔΙ. ΦΥΣΙΚΑ ΚΑΙ ΧΑΡΗΚΑ ΤΟ ΑΠΟΤΕΛΕΣΜΑ. ΑΛΛΑ ΠΙΟ ΠΟΛΥ ΧΑΡΗΚΑ ΤΗΝ ΠΙΚΡΑ ΣΤΗΝ ΦΩΝΗ ΤΟΥ ΚΑΡΑΓΚΙΟΖΗ ΠΟΥ ΜΕΤΕΔΙΔΕ ΤΟ ΜΑΤΣ !! ΤΙ ΗΤΑΝ ΑΥΤΟΣ ΡΕ ΠΑΙΔΙΑ . Ο ΤΣΟΥΚΑΛΑΣ ΠΙΟ ΑΝΤΙΚΕΙΜΕΝΙΚΟΣ ΘΑ ΗΤΑΝ !!!
kostas 21
αντε γεια αντε γεια. το κυπελο το χασαμε παιδιααααααα, Τ. ΤΣ
foros 21
zikoooooooooooo!!!!!!!!!! ti epathes stis seres bre!!!!!!!
Babylon21
emeis na ta vlepoume....
r21
kolosate gatoules. gauroi r@@@ kotopoula me krani
Μάκης - Αθήνα
Eμείς να τα βλέπουμε αυτά...
Δεν υπήρχαν για ένα ημίχρονο στο ΟΑΚΑ, και όμως κέρδισαν! Άθλια ομάδα, θα πάθει πολλά τέτοια φέτος, γιατί απλά οι παικταράδες του Ζίκο δεν τρέχουν, περπατάνει..
Μπράβο στα "λιοντάρια" των Σερρών!
ALEXSAXIB
Επιτέλους άρχισε να φαίνεται το πραγματικό πρόσωπο αυτής της ομάδας... Όχι τίποτε άλλο αλλά μας έπρηξαν ότι και καλά έχουν ποιοτικούς παίκτες και παρόμοιες ανοησίες. Γυμνοί ήταν, γυμνοί είναι... μικρή ομάδα, μικρός προπονητής. Θα ακολουθήσουν πολλές ακόμα ήττες. Έχουμε να γελάσουμε πολύ
kosmas
ΟΟΟΟΟΟΛΛΛΛΕΕΕΕΕ!!!!! ΟΥΣΤ ΑΠΟ ΔΩ ΧΑΡΤΙΝΟΙ ΚΛΕΦΤΕΣ ΥΓ: ΣΕΒΑΣΜΟΣ ΣΤΙΣ ΣΕΡΡΕΣ! 3 ΣΤΟΝ ΒΑΖΕΛΟ 3 ΚΑΙ ΦΕΤΟΣ ΣΤΟΝ ΘΡΗΝΟ! ΕΕΕΛΑ ΜΩΡΗ ΠΑΝΣΕΡΡΑΙΚΑΡΑΑΑΑΑΑΑΑΑΑΑΑΑΑΑΑΑ
adriano
Τι έγινε ρε παιδιά δεν μίλησε η καρδιά του χάρτινου πρωταθλητή ; Μουγγάθηκε ;
ΕΤΣΙ , ΕΤΣΙ .......... ΒΕΝΤΟΥΖΑΑΑΑΑΑΑΑΑ
Braveheart
Φτού σας ρε... που χαίρεστε επειδή αποκλείστηκε ο θρύλος.

Με τι θα γελάμε αύριο ε;

Τώρα που οι έμμισθοι κονδυλοφόροι δεν θα μπορούν να εκθειάζουν την Καρδιά του Πρωταθλητή....

Γιατί θα γράφουν τώρα ε;

Για τη νεφραμιά του Πρωταθλητή;

Είναι αστείο αυτό ε;
Dimitris21
Ρε παιδιά τα πράγματα είναι άπλα ο Γαύρος έπαιξε όπως παίζει μέχρι τώρα τίποτα το διαφορετικό απλά σήμερα έλειπε η κωλοφαρδία του Κηπουρού!!Ο Ζηκο λίγο ακόμα και θα έβαζε τα κλάματα!!! χαχαχαχαχαχα!! ΠΑΜΕ ΡΕ ΑΕΚΑΡΑΑΑΑΑ!!!!!
dolmance
Re paidia??Pou pige i kardia prwtathliti kai to metalo tou?Ah re sportday avrio tha exeis mavro protoselido gia tin thrilara sou krima
Dimitris21
Ρε παιδιά τα πράγματα είναι άπλα ο Γαύρος έπαιξε όπως παίζει μέχρι τώρα τίποτα το διαφορετικό απλά σήμερα έλειπε η κωλοφαρδία του Κηπουρού!!Ο Ζηκο λίγο ακόμα και θα έβαζε τα κλάματα!!! χαχαχαχαχαχα!! ΠΑΜΕ ΡΕ ΑΕΚΑΡΑΑΑΑΑ!!!!!
PAPPOUS
Η ΕΥΚΑΙΡΙΑ ΤΟΥ ΜΗΤΡΟΓΛΟΥ ΗΤΑΝ ΟΦΣΑΙΝΤ. Ο ΤΕΡΜΑΤΟΦΥΛΑΚΑΣ ΕΙΧΕ ΒΓΕΙ ΚΑΙ ΤΟΝ ΚΑΛΥΠΤΕ ΕΝΑΣ ΠΑΙΚΤΗΣ ΜΟΝΟ. ΟΙ ΕΚΦΩΝΗΤΕΣ ΓΙΑ ΚΛΑΜΑΤΑ. ΣΤΟ ΠΕΝΑΛΤΙ ΤΟΥ ΠΑΝΣΕΡΡΑΙΚΟΥ ΦΩΝΑΞΕ ΟΦΣΑΙΝΤ ΕΝΩ Η ΠΑΣΑ ΕΓΙΝΕ ΑΠΟ ΤΗ ΓΡΑΜΜΗ ΠΡΟΣ ΤΑ ΠΙΣΩ ΚΑΙ ΣΤΟ ΤΕΡΜΑ ΗΤΑΝ 3 ΠΑΙΚΤΕΣ ΤΟΥ ΓΑΥΡΟΥ. ΣΗΜΕΙΩΣΤΕ. ΤΟ ΠΕΝΑΛΤΙ ΤΟ ΕΔΩΣΕ Ο ΒΟΗΘΟΣ.
ΠΑΝΤΩΣ, ΚΡΙΜΑ ΕΙΝΑΙ ΚΑΙ ΓΙΑ ΤΗΝ ΑΕΚ ΠΟΥ ΔΕ ΜΠΟΡΕΣΑΜΕ ΝΑ ΚΕΡΔΙΣΟΥΜΕ ΟΠΩς Ο ΠΑΝΣΕΡΡΑΙΚΟΣ
YiAndronix
Να και τα ευχάριστα σήμερα. Κ. . . . . φαρδία ΤΕΛΟΣ.
Όνομα
den nomizo na eine lalakas o kokalis.to tameio einai mion 30 kai kati miria.tha kanei ta panta na parei to protathlima,kai na ferei to tameio sto 0.alitheia poso edine to stoixima ston asso?
GEORGE 21
ΑΝΥΠΑΡΚΤΟΣ Ο ΓΑΥΡΟΣ!ΞΕΦΤΙΛΗΣΤΗΚΕ ΤΟ ΚΟΚΚΙΝΟ ΠΑΡΑΜΥΘΙ......
ΜΙΧΑΛΗΣ
ΥΠΕΡΟΧΗ ΝΥΧΤΑ!!!!

nickpet21
Τι εγινε ρε μαγκες;
Ο ηρωας ο Ζικο που επαιρνε τα παιχνιδια στο παρα 5, ενω επρεπε να τα χανει, τωρα τον στησατε στον τοιχο;
Σε ευχαριστω Θεε μου προκαταβολικα γι αυτα που θα δουμε και θα ακουσουμε τις επομενες μερες.
Κωλογαυροι ωραιος ο ακανες;
SOUFLIAEK
ΗΔΟΝΗ
ΚΑΙ ΚΛΑΜΑ Ο ΔΑΛΟΥΚΑΣΣΣΣΣΣΣΣ
xristos
ενα προπονητη θελουμε επιτελουσ..ο ογιοσ απαντησε στισ δικαιολογιεσ του ντουσαν..
Dimitris21
Ρε παιδιά τα πράγματα είναι άπλα ο Γαύρος έπαιξε όπως παίζει μέχρι τώρα τίποτα το διαφορετικό απλά σήμερα έλειπε η κωλοφαρδία του Κηπουρού!!Ο Ζηκο λίγο ακόμα και θα έβαζε τα κλάματα!!! χαχαχαχαχαχα!! ΠΑΜΕ ΡΕ ΑΕΚΑΡΑΑΑΑΑ!!!!!
Ermolaos
Telika...yparxei Theos!!!
nikolas
paidia mhn psaronete o gayros aurio tha kanei enstash kai tha to parei to mats sta xartia ....
Όνομα
ο διορισμενος [[πρωταθλητης]] παλι μας εκανε να γελασουμε....για γελια πολλα ηταν....οταν παιζεις κανονικα και χωρις [βοηθεια] ξερεται τι εννοω...ο [νταπλουχος] πρωταθλητης θα μας χαριζει καθε κυριακη αφθονο γελιο...
ackis
Ζήτω οι προσφυγικές ομάδες,
κάτω οι ομάδες της διαφθοράς και του παρασκηνίου, της (Stazi το ταβάνι), και της παράνγκας.
Ζήτω η άξια ομάδα του Πανσεραικού, καλή τύχη στην συνέχεια.
Ο ΟΦΣΠ εκεί που του αξίζει, στόν σκουπιδοτενεκέ στο χρονοντούλαπος της ποδοσφαιρικής ιστορίας, γιά όλους τούς άδικους, γιά όλους τους διεφθαρμένους.
Τέρμα το Kokalistan έρχεται νέα βυζαντινή εποχή. Πάρτε δύναμη, χαρά κα αγαλλίάση έρχεται ο Bob μαζί με όλους μας θα τα καταφέρουμε να δώσουμε τέλος στην δικτατορία της παράνγκας καί της διαφθοράς της Ελλάδος.
Ντέμαρε πάντα χρειαζόμαστε την αγνή ΑΕΚντζήδηκη ψυχή σου,έλα ξανά δίπλα στην ΑΕΚάρα.
Ολοι μαζί, ΕΝΩΣΗ.
Dimitris21
ΑΑΑΑΑ ΚΑΙ ΕΝΑ ΜΠΡΑΒΟ ΣΤΟ ΕΠΟΠΤΗ ΠΟΥ ΥΠΟΔΕΙΞΕ ΤΟ ΧΕΡΙ ΤΟΥ ΠΑΠΑΔΟΠΟΥΛΟΥ ΓΙΑΤΙ Ο ΔΙΑΙΤΗΤΗΣ ΧΑΜΠΑΡΙ ΔΕΝ ΕΙΧΕ ΠΑΡΕΙ.....
Dimitris21
ΑΑΑΑΑ ΚΑΙ ΕΝΑ ΜΠΡΑΒΟ ΣΤΟ ΕΠΟΠΤΗ ΠΟΥ ΥΠΟΔΕΙΞΕ ΤΟ ΧΕΡΙ ΤΟΥ ΠΑΠΑΔΟΠΟΥΛΟΥ ΓΙΑΤΙ Ο ΔΙΑΙΤΗΤΗΣ ΧΑΜΠΑΡΙ ΔΕΝ ΕΙΧΕ ΠΑΡΕΙ.....
TT1981
ΠΑΙΔΙΑ ΣΤΕΙΛΤΕ Ε-ΜΑΙL ΣΤΟΝ ΑΛΦΑ ΣΤΟ pr@alphatv.gr

ΑΝ ΕΙΝΑΙ ΔΥΝΑΤΟΝ ΜΕ ΤΟΝ ΚΑΡΑΓΙΟΖΗ ΤΟ SPEAKER!!!!
kostas ΠΕΙΡΑΙΑΣ
ρε κοκκαλιάρη μην είσαι τσιγκούνης. Πλήρωσε τους δαλούκες και στα εύκολα παιχνίδια να έχεις το κεφάλι σου ήσυχο.
Γαύροι μ****ά ντροπή του Πειραιά
ΠΟΛΥΚΑΡΠΟΣ
APO 3ARA SE 3ARA OI SERRES MIA SE PAO KAI TORA OSFP ΛΟΛ!! ΑΝΤΕ ΝΑ ΑΠΟΚΛΕΙΣΤΕΙ ΚΑΙ Ο ΒΑΖΕΛΟΣ ΚΑΙ ΝΑ ΤΟ ΣΗΚΩΣΟΥΜΕ ΓΙΑΤΙ ΕΤΣΙ ΟΠΩΣ ΕΙΝΑΙ Η ΟΜΑΔΑ ΜΑΣ(ΚΑΙ Η ΔΙΑΤΗΣΙΑ) ΔΕΝ ΕΧΟΥΜΕ ΕΛΠΙΔΑ ΝΑ ΠΑΙΖΟΥΜΕ ΜΑΖΙ ΤΟΥΣ
mixalis rodos 2009
san klameno M.... htane o ZHKOS
SERRES21
GIATI POLY APLA THRILOS EINAI O PANSERRAIKOS K OXI O @@@ O OLYMPIAKOS!!!!!!!!!!!!!!!
dikefaleThaTrelathw
xaaaaaaaaaaaaaxaxaxaxaxaxa na se kala re thryne kairo eixa na gelasw etsi . Pantos thelw na dw tha synexizoun na sas xaideuoun ta aftia oi dhmosiografoi ?
omd
Αντε Ντουσαν παρε καμια ιδεα πως παιζετε το τόπι γιατί βγηκανε τα ματια μας μάυτά που βλέπουμε. Ογιος δεν ερχεσαι απο Θρακομακεδόνες μερια μήπως κι αλλαξουμε κανα δυο πάσες?
Α που σαι Ντούσαν! Οι Σέρρες έπαιξαν μπαλάρα και στα 2 ημίχρονα...
panos21
Ο Θεός τους πήρε πίσω, αυτό που μας στέρησε περυσι το Μάη στο 96.......
Demis21
Κριμα ρε παιδια....τους ηθελα τελικο..
knikos21
ΡΟΜΠΑ ΤΟ ΟΛΥΜΙΑΚΑΚΙ!!!
Madbutcher
κοιτα απο ποιους χανουμε το πρωταθλημα,γ*μω τη καταδικη μου
aektzis o rodios!
mhn me geloun ta matia mou?mhn me 3egeloun tautakia mou?mhpws zw se ena paralogo oneiro???ti glukia hdonh htan auth pou elaba shmera!!eeeetsi!!!kai tora welcome to the machine!!ainte giati me daloukes kai maurra korakia den ginete mia zwh na kerdizoun!!!tous mpip me sklhra faoul kai oi bentetes ta eidan skoura!!!
nick777
Γκιγιέρμο Όγιος vs Μπάγιεβιτς = ???
jijj
DEITE TI LEGANE TA GAVRAKIA XTHES..XAXA...GELIOI TYPOI

http://gavros.gr/Default.aspx?id=40909&nt=108&lang=1
ΚΩΣΤΑΣ ΑΜΠΕΛΩΝΑΣ ΛΑΡΙΣΑΣ
ΟΤΑΝ ΤΟΥΣ ΠΑΙΖΕΙ Η ΔΙΑΙΤΗΣΙΑ 50-50 ΔΕΙΧΝΟΥΝ ΤΟ ΠΡΑΓΜΑΤΙΚΟ ΤΟΥΣ ΠΡΟΣΩΠΟ ΤΟ ΑΘΛΙΟ ΟΛΩΝ ΤΩΝ ΕΤΩΝ ΕΙΔΑΤΕ ΤΑ ΠΑΙΔΙΑ ΤΟΥ ΠΕΙΡΑΙΑ(ΚΑΦΡΟΙ) ΜΑΣ ΘΑΜΠΟΣΑΝ ΠΑΛΙ ΣΕΡΕΣ ΣΕ ΕΥΧΑΡΙΣΤΗ ΟΛΟΙ Η ΕΛΛΑΔΑ
sid
Επιτέλους Ξεγυμνώθηκαν οι Κωλόφαρδοι !!!

Σειρά σας βαζελάκια !!!
ΑΕΚg
Υποτίμησε το παιχνίδι ο ολυμπιακός και για αυτό έχασε.

ΠΟΥ ΠΑ ΡΕ ΚΑΡΑΜΗΤΡΟ ΧΩΡΙΣ ΔΑΛΟΥΚΑΑΑΑ;;;;;
maskoforos21
re paidia einai adiko.ligo poly oloi ton thelame ston teliko na paroume ekdikisi.alla fimes lene oti o rimoldi kai o athanasiadis epaizan xwris deltio.kokkali gera parto sta xartia.
BOKO 21
βαλτε μεσα τον δαλουκα!!!
panos_21
OLOI E MAIL STON ALPHA GIA TI DROPI POY MAS ANAGAZOYN NA AKOYME...........ELEOS.....STEILTE E MAIL ADERFIA....OLOI....VARETHIKAME TI XOYDA TOU KOKKALI
christoss21
mallon 3exase o 8eios na parei kanena thlefwno h phre kai eide oti o gagatshs leipei pia
xaos
paidia μην ωαιρεστε και πολυ...................
μπορει να κανει ο γαυρος ΕΝΣΤΑΣΗκαι να το παρει στα χαρτια, ΟΛΑ ΤΑ ΕΧΟΥΜΕ ΔΕΙ ΜΕ ΤΟΝ ΓΑΥΡΟ
xarat
etsi oxi tipota allo na vgaloume kai kana frago apo to stoixima
xaos
paidia μην Χαιρεστε και πολυ...................
μπορει να κανει ο γαυρος ΕΝΣΤΑΣΗ και να το παρει στα χαρτια, ΟΛΑ ΤΑ ΕΧΟΥΜΕ ΔΕΙ ΜΕ ΤΟΝ ΓΑΥΡΟ
ΓΙΑΝΝΗΣ 33
ΣΑΣ ΣΑΨΑΛΩΣΕ Ο ΠΑΝΣΕΡΡΑΙΚΟΣ ΓΑΥΡΑΚΙΑ!!!
ΧΑΧΑΧΑΧΑΧΑΧΑΧΑΧΑΑΑΑΑΑΑΑΑΑΑ... ΤΙ ΦΑΠΑ ΣΒΟΥΡΙΧΤΗ ΗΤΑΝ ΑΥΤΗ!!!!!
ΑΛΛΑ ΘΑ ΒΓΕΙ Ο ΝΙΚΟΛΑΚΟΠΟΥΛΟΣ ΚΑΙ ΘΑ ΠΕΙ ΟΤΙ ΦΤΑΙΕΙ Ο ΚΕΤΣΠΑΓΙΑ!!!!!
aeki marseillais
wx apo tetarti tha xoume episkepseis ston pilavio pali gt den tous epaikse 100-0 i diaitisia kai giati apevalle ton papadopoulo afou oute xeri itan oute to thele oute epireaze.
na rwtisw kai kati ksereis kaneis apo pou pan sta SERRAS???????????/
Scocco32
ETSI.....APLA KAI OMORFA....WS POTE 8A KERDIZAN OI KWLOFARDOI OI XARTINOI KAI OI KLEFTES.....
O VLAXOS O MITROGLOU PANIGURIZE POU MEIOSE ME TIS SERRES,KAI OFSIDE SE ADEIO TERMA TO STEILE STIN KAVALA XAXAXAXAXAXA
NA DW AURIO TI SKATA 8A LENE OTI EPA8E I KARDIA TOU PROTA8LITI TROMARA SAS...!!!!
giannis speed
mia mono leksi perigrafei t sinasthimata p niwthw gia tn apokleismo t gaurou!!!k@@@@!!!!megali xara...sxedon anatrixiasa...ola ksafnika arxisa na t vlepw pio wraia...ma ola....paidia egw tn speaker dn tn akousa gt dn eida tn agona alla an ontws simperiferotane opws eipate na zitisoume na diwxthei apo tv na mn ksanaperigrapsei agona...m olous tous karagkiozides p exoume mpleksei...s ola t kanalia net ant1 alpha iper panathinaikou osfp k enantion aek...oust re poulimenoi....
μακαρος
θρυλε γερα παρτο στα χαρτια!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
gl_21
swstos o TT1981...to parakane...supersport to kanane...alla tous timwrhse shmera...ferte ton anakoglu k ton athanasiadh k dwste mako,yahagia,paulh...poli mpalla!
alex21p.faliro
xaxaxaxaxa oi ampaloi

thryle gera kai parto sta xartia
karagkiozhdes GAYroi
geezer21
KANTE ENSTASI KANTE ENSTASI!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
XEFTILISMENOI!!!!!!!!!!!!!!!!!!!!!!!!!
FERTE PISO TON GAGATSI!!!!!!!!!!!!!!!!!!!!
HarrisPi
Εγω εχω καταντησει να βλεπω ποδοσφαιρο με κλειστη φωνη.
Φατε τη φουτσα των Σερρων καφροι. Τρια παιχνιδα στα τελευταια λπτα και με τη βοηθεια του κορακιου. Τωρα να σας δω που θα παρετε τηλεφωνο ?
2
ligise i kardia tou protathliti....
i armada-germada tou ziko den katafere tin 3i anatropi gia na grapsei me xrysa grammata to onoma tis sto thesmo tou kypellou
aekara mia zwh aderfia
δεν θα ηταν σωστος ο διαιτητης μαλλον.....χαχαχαχαχαχαχ ετσι ειναι αυτα δεν εχεις παντα τον δεκατοτεταρτο παιχτη μαζι σου[διαιτητης και εποπτες}...χαχαχ αντε ρε κολογαυροι..παει το ενα για φετος....αν χασετε και το αλλο απο την αεκαρα τοτε θα γελαμε τρελα για μια ζωη...παμε ρε αρρωστια αεκ δειξε ποια εισαι με ενα κυπελλο.
gl_21
swstos o TT1981...to parakane...supersport to kanane...alla tous timwrhse shmera...ferte ton anakoglu k ton athanasiadh k dwste mako,yahagia,paulh...poli mpalla!
skoco 21
φορα δεν επαιξε το super φαρδος ο κηπουρος και αμεσως φανηκε οτι ειναι και λιγοι αλλα και τυχεροι τοσο καιρο!αν βαλεις οτι επιτελους καποιος καταλαβε οτι volley παιζουν σε αλλα γηπεδα και σφυριξε πεναλτι εναντιον τους,τοτε ολα γινονται πολυ απλα!αντε γεια τωρα!
max bos
Ρε παιδια, ποσο κανουν οι κορνεδες σημερα? Λεω να φορτωσω και να παω Ρεντη αυριο. Βλεπω τρελα κερδη
sid
Αυτό δεν ήταν μπανάνα,
Αυτό ήταν Π@@@

ΕΓΚΛΗΜΑ ... ΧΩΡΙΣ ΤΙΜΩΡΙΑ

Καρκινοπαθείς: Έγκλημα οι χημειοθεραπείες από απλούς παθολόγους

Χημειοθεραπείες χωρίς την παρουσία ειδικού γιατρού φαίνεται ότι γίνονται σε διάφορα νοσοκομεία της Βόρειας Ελλάδας. 

Της Νικολέτας Μπούκα

Όπως καταγγέλλουν στη “ΜτΚ” οι ίδιοι οι καρκινοπαθείς, απλοί παθολόγοι, χωρίς ειδικότητα στην ογκολογία, όπως προβλέπει ο νόμος, αναλαμβάνουν να χορηγήσουν στους ασθενείς τα απαραίτητα για τη θεραπεία τους φάρμακα

Ωστόσο τα φάρμακα αυτά είναι τοξικά και η δοσολογία συγκεκριμένη, με αποτέλεσμα να τίθεται σε κίνδυνο ακόμη και η ζωή των ασθενών, αφού στη διάρκεια της χημειοθεραπείας μπορεί να παρουσιαστούν σοβαρά προβλήματα, τα οποία είναι αδύνατον να αντιμετωπιστούν από μη ειδικό γιατρό.
Χαρακτηριστική είναι η περίπτωση του νοσοκομείου των Σερρών, όπου, σύμφωνα με τους καρκινοπαθείς, στις 29 Ιουνίου του 2007 άρχισε να λειτουργεί μονάδα χημειοθεραπείας, χωρίς να προΐσταται γιατρός ογκολόγος-παθολόγος, μία ειδικότητα που είναι θεσμοθετημένη και αναγνωρισμένη από το ελληνικό δημόσιο από το 1998 (Π.Δ. 204/98).
“Δυστυχώς σε πολλές περιπτώσεις η κατάσταση είναι ανεξέλεγκτη και άρα επικίνδυνη για τους καρκινοπαθείς. Παρόμοιες περιπτώσεις μ’ αυτήν του νοσοκομείου Σερρών συναντάμε και σε άλλα νοσηλευτικά ιδρύματα, όπως της Καβάλας, της Κοζάνης και της Βέροιας. Οι γιατροί στις μονάδες χημειοθεραπείας των νοσοκομείων αυτών δεν είναι παθολόγοι-ογκολόγοι, ενώ συχνά η χορήγηση των δόσεων των φαρμάκων γίνεται με οδηγίες μέσω… τηλεφώνου”, δηλώνει στη “ΜτΚ” η πρόεδρος του Συλλόγου Καρκινοπαθών Μακεδονίας-Θράκης Περσεφόνη Μήττα.
Παράλληλα εξηγεί ότι πλέον η διάγνωση της νόσου γίνεται στη Θεσσαλονίκη και οι ειδικοί γιατροί δίνουν την προβλεπόμενη θεραπεία, η οποία γίνεται στις μονάδες χημειοθεραπείας των περιφερειακών νοσοκομείων.
“Η χημειοθεραπεία δεν είναι κάτι απλό. Μιλάμε για χορήγηση τοξικών φαρμάκων σε ανθρώπους. Πώς μπορεί ένας απλός παθολόγος και όχι παθολόγος-ογκολόγος να κάνει μίξη των φαρμάκων και ποιες είναι οι δόσεις που χορηγεί; Αν γίνει έστω κι ένα λάθος ή προκληθούν παρενέργειες από τη θεραπεία, ποιος θα φροντίσει άμεσα τον ασθενή; Η άγνοια σε τέτοια λεπτά ζητήματα μπορεί να θέσει σε κίνδυνο την ίδια τη ζωή του ασθενούς”, επισημαίνει η κ. Μήττα.

ΧΕΙΡΟΥΡΓΕΙΑ ΑΠΟ ΜΗ ΟΓΚΟΛΟΓΟΥΣ
Την ίδια στιγμή εγκληματικά είναι και τα λάθη που γίνονται κατά τη διάρκεια των χειρουργικών επεμβάσεων σε ασθενείς με καρκίνο. Σύμφωνα με την κ. Μήττα, οι χειρουργοί, οι ορθοπεδικοί και οι γυναικολόγοι που ασχολούνται με καρκινοπαθείς δεν έχουν την ειδικότητα του ογκολόγου.
“Πώς είναι δυνατόν ένας γενικός χειρουργός ή ορθοπεδικός να μπορέσει να αντιμετωπίσει έναν άνθρωπο με καρκίνο; Έχουν ανοίξει στη Θεσσαλονίκη δύο τμήματα χειρουργικής μαστού, χωρίς οι γιατροί να είναι ογκολόγοι. Πώς μπορούν οι άνθρωποι αυτοί να διαγνώσουν τον καρκίνο και να τον αντιμετωπίσουν;

Προσωπικά, εξαιτίας της έλλειψης ογκολόγου, κινδύνεψα να χάσω το πόδι μου”, λεει η κ. Μήττα. Σύμφωνα με την ίδια, με το πέρασμα των χρόνων πολλοί γιατροί έχουν αποκτήσει εμπειρία και στην αντιμετώπιση περιστατικών με καρκίνο. Ωστόσο αυτή δεν είναι η λύση στο πρόβλημα. Είναι αναγκαία η τοποθέτηση ειδικευμένων ογκολόγων σε όλους τους τομείς της ιατρικής.
“Υπάρχουν πολλές περιπτώσεις, όπου έγιναν τραγικά λάθη από μη ογκολόγους γιατρούς. Γιατρός ‘έκαψε’ το έμβρυο, διότι νόμιζε ότι επρόκειτο για καρκίνο, ενώ άλλος χορήγησε χημειοθεραπεία σε γυναίκα που ήταν έξι μηνών έγκυος. Επιπλέον έχουμε και περιστατικά, όπου άνθρωποι μπήκαν στο χειρουργείο και τους έγινε ακόμη και αφαίρεση μαστού χωρίς να χρειάζεται. Είναι επιτακτική ανάγκη να σταματήσουν να γίνονται τέτοια λάθη”, εξηγεί η κ. Μήττα.
Παράλληλα προτείνει την ενίσχυση των νοσηλευτικών ιδρυμάτων και των τμημάτων που απευθύνονται σε καρκινοπαθείς με εξειδικευμένο προσωπικό, το οποίο σήμερα δεν επαρκεί, καθώς και τη δημιουργία ογκολογικών συμβουλίων, τα οποία λειτουργούν σε Ευρώπη και Αμερική. Αυτά θα απαρτίζονται από έναν καθηγητή ογκολογίας, ένα κυτταρολόγο κι ένα παθολόγο-ογκολόγο, οι οποίοι θα συναποφασίζουν για την καταλληλότερη θεραπεία ενός ασθενούς, δηλαδή, εάν ένα περιστατικό με καρκίνο πρέπει πρώτα να χειρουργηθεί και μετά να υποβληθεί σε χημειοθεραπεία ή το αντίθετο.
“Με τον τρόπο αυτό, οι ειδικοί θα αποφασίζουν για την πιο κατάλληλη θεραπεία και θα αποφεύγονται τυχόν λάθη και παραλείψεις. Δεν είναι τυχαίο ότι σήμερα, όπως ομολογούν οι ίδιοι οι γιατροί, σχεδόν οκτώ στις δέκα επεμβάσεις σε καρκινοπαθείς, δεν έπρεπε να έχουν γίνει”, λεει η κ. Μήττα.

ΑΥΤΑ ΒΛΕΠΟΥΝ ΟΡΙΣΜΕΝΟΙ ΚΑΙ ΠΡΟΣΠΑΘΟΥΝ ΝΑ ΤΑ ΜΙΜΗΘΟΥΝ. ΕΔΩ ΕΙΝΑΙ ΟΜΩΣ ΒΑΛΚΑΝΙΑ...

Forty Years' War

A Place Where Cancer Is the Norm

By GINA KOLATA
Published: October 24, 2009

HOUSTON — M. D. Anderson Cancer Center has a mission statement, and everyone who works there, from the president to the cleaning crews, can state it like a catechism: to “eliminate cancer in Texas, the nation and the world.”

For the nearly 90,000 patients who will go to the center in Houston this year, that mission cannot be fulfilled soon enough. They and their families arrive at the world’s largest freestanding cancer hospital from around the world, often leaving behind jobs and stashing children with relatives for months. Some rent apartments or stay in mobile home parks near the hospital.

They enter through a soaring lobby, with cheery aquariums and exuberant volunteer greeters eager to help in any way. They come looking for hope.

But there is no mistaking what this place is: the front line of the frustrating war on a still largely incurable disease.

Doctors are encouraged to try everything, and when insurers balk, they pick up the phone, repeatedly, hoping to persuade them to pay for what may be unconventional treatments.

The federal government gives more cancer research money to this hospital than to any other, and the hospital has an abundance of specialists in many forms of cancer, including rare ones. Medicare offers more generous reimbursement, and the hospital offers treatments that often go far beyond what can be offered at most other places.

“I tell young physicians who are starting out here that the big limitation is imagination,” said Dr. Martin Raber, an oncologist — and a cancer patient himself — at Anderson. “If you are good at what you do and you have great ideas, we will help you find the resources you need to make them happen.”

But like a modern version of the tuberculosis sanatorium in Thomas Mann’s “Magic Mountain,” Anderson is a world where the best that medicine has to offer is often far from enough. The odds are still grim, and while there are exhilarating recoveries, the exhausting, dispiriting road traveled by many patients comes into sharp relief.

They are patients like 35-year-old Mindy Lanoux of San Antonio, who has melanoma that has spread to her liver and lungs, her odds of surviving in the single digits. She has been to the hospital 16 times in nine months, spending a week there each time for treatments so debilitating she wanted to give up. But she keeps returning, smearing peppermint oil under her nose when she walks in the medical center’s door to hide the odor.

“The smell gets to me,” Ms. Lanoux said. “It smells like cleaning products and the sickness and the medicines. It takes your brave edge off.”

Then she and her father go to her room and start putting her things away. “We don’t talk,” Ms. Lanoux said. “There is no polite conversation. It is like an army setting up to do battle.”

Planet Cancer

With more than 17,000 employees and warrens of color-coded hallways so vast that even employees get lost, M. D. Anderson is its own parallel universe, where nothing matters but cancer. Patients sit in the lobbies and compare notes.

“Everyone in the waiting room talks about ‘How did you find yours?’ ” said June Toland, 71, of Harlingen, Tex., who is being treated for sarcoma, a cancer of connective tissue.

Every patient at Anderson has cancer. Every family member sitting anxiously in the lounges or lingering at a bedside or sleeping in a Murphy bed in a patient’s room has had the life-changing experience of being touched by cancer.

“It feels sometimes like the entire world has cancer,” said Cindy Davis, a nurse in the breast cancer clinic who has breast cancer herself.

Anderson is a quiet place. No loud pagers. The walls are decorated with vivid photographs of serene scenes, like water views. The muted colors in the hallways, soft cranberry and dull green, are meant to be soothing. There is a special room, Kim’s Place, for young people only, cancer patients and their friends ages 15 to 30, giving them a place to gather. There is a library and a cybercafe. It is a place meant to give hope.

Sometimes, as happened with Frances Anderson of Shreveport, La., that hope is realized. She discovered three years ago that she had a brain tumor, but it did not start in her brain. In fact, it is not clear where it started. After being told by a doctor elsewhere that she had four to seven months to live, she ended up at Dr. Raber’s clinic, one of the few that specialize in treating patients with cancer throughout their bodies but with no obvious source for the tumors.

At 66, wearing pressed jeans, her short blond hair carefully styled, Ms. Anderson has vision problems from the surgery to remove the brain tumor, and she gets tired. She still has cancer, but she exercises every day and is living with her disease, returning to Anderson every six months for checkups and scans.

Others are not so fortunate. One morning last month, Joe Maxwell, 52, sat in a chair next to his hospital bed, a compression bandage around his now-useless swollen left arm, a large bandage over his left shoulder. He was going home to sit on his deck in Kerrville, Tex., a four-hour drive. He had tried everything Anderson had to offer and decided that, with an estimated two weeks left, he would go home to die.

Mr. Maxwell came to Anderson in January after his doctor told him a bump on his shoulder was a rare tumor, Merkel cell carcinoma, and added, “If you have a rare tumor, you need to go where tumors are not rare.”

At Anderson, doctors tried everything they could think of — surgery, round after round of chemotherapy, a clinical trial of an experimental drug. Nothing worked. Finally, the doctors suggested yet another drug.

“We spent a lot of time praying about it and just discussing it,” Mr. Maxwell said. “I wanted to go home; I was tired. They gave me a short amount of time and said, ‘If you want to go home, now is the time.’ ”

But leaving late last month was bittersweet. The doctors and nurses “have become our friends and our family,” his wife, Kathleen Maxwell, said. Anderson, she added, “has been our life for nine months.”

He died 10 days later, early in the morning of Oct. 8.

Even those who finish their treatments and live cancer-free are forever changed by the experience.

Mrs. Toland learned that lesson from her son, George Toland. Twenty-four years ago, when he was 21, he was a sarcoma patient at Anderson. One day he looked at his mother and said, “My life will never be the same.”

His mother tried to reassure him, telling him that he would be fine, that he would go on to a perfectly normal life.

But he demurred, saying, “You know, Mother, it’s a loss of innocence.”

Mrs. Toland knew he was right.

She told him: “Most people lose their innocence in little doses as they go through life. You lost yours all at once.”

Battling the Odds

Donald Berry, a statistician who is head of the division of quantitative sciences at Anderson, says part of his role at the cancer center is to provide a reality check.

Yes, it is true, as doctors and nurses there repeatedly say, that treatment has improved. Anti-nausea drugs have all but eliminated the constant vomiting that once accompanied chemotherapy. New drugs are attacking genes that go awry in cancer. Most cancer patients come and go over a period of years, for checkups, scans, treatment if the cancer is still there. In between they go on with their lives.

But there is still little that can be done for most of those whose cancer has spread. And, Dr. Berry said, “that is a fact that doctors at M. D. Anderson can have a hard time facing, understandably so.”

Dr. Russell Harris, an associate professor of medicine at the University of North Carolina and a member of a board that evaluates cancer therapies for the National Institutes of Health, said the temptation at major cancer centers like Anderson was to try treatment after treatment.

“Everyone is totally immersed in the idea that death is the enemy,” Dr. Harris said. Such a no-holds-barred stance, he added, is spurring a growing debate in the cancer community.

“There is a lot of concern within the oncology community right now, and appropriately so, that people don’t completely understand what they are getting into,” Dr. Harris said.

An aggressive — and expensive — course of treatment can place a huge burden on patients. Ms. Lanoux knows that all too well. She came hoping for a cure for her advanced melanoma, but got her first dose of reality the day she walked into the main lobby.

She saw patients in wheelchairs, their heads sunken on their chests. She saw patients who had lost their hair, patients wearing sky-blue masks to protect them from infections. And there were the children. She had to avert her eyes. “I still can’t look at the kids,” Ms. Lanoux said.

“I think we were all trying to be very brave,” she said. “But it was like walking into a coffin.”

Ms. Lanoux, a small blond English teacher, lives in San Antonio with her husband, also a teacher, a 19-month-old daughter, an 8-year-old daughter and a 12-year-old son. The day she arrived at Anderson, Feb. 9, was the beginning of a difficult journey at the cancer center. She has been coming about every three weeks since, staying for a week at a time.

Her problems began in August 2008 on the way to a beach vacation. She started coughing. Her doctor was not concerned, telling her he thought she had acid reflux because she had had it when she was pregnant. He gave her Nexium. She returned in November at a friend’s urging, and her doctor prescribed cough drops and steroids. But she kept coughing.

Finally, in January, when she still could not catch her breath, her doctor ordered a chest X-ray to see if she had bronchitis. The next week, she returned to learn the result. Her husband wanted to go with her, but she told him not to bother, it was probably just bronchitis.

The doctor “came in and said, ‘This is the part I hate most about being a doctor,’ ” Ms. Lanoux recalled. There was a spot on her lung. A CT scan also revealed spots on her liver. And a biopsy of the spots on her liver revealed what it was. Melanoma. It had spread from an initial lesion — no one could ever find where it started — and was now threatening her life.

Ms. Lanoux’s doctor in San Antonio told her to go to Anderson. “She very honestly told me, ‘I don’t want to try treating you,’ ” Ms. Lanoux said.

“I think I was in denial until last month,” she said. “I had a 10 percent chance to survive five years, and I was going to do it.”

She has tried everything. Immunological therapy with side effects so severe it has to be administered in the intensive care unit. It did not work. Then she started biochemotherapy — a combination of three chemotherapy drugs and two immune system hormones to stimulate her body to attack her tumors. It is a controversial treatment, said her doctor, Patrick Hwu, but some patients had lasting remissions.

Not Ms. Lanoux. At least not yet. On a recent sunny fall afternoon, she lay in her hospital bed on the 10th floor, wearing striped pajamas, blinking away tears as she told her story. She had just finished her sixth biochemotherapy treatment. Once again, she said, the therapy had made her feel “barely human.”

The effects hit her hard after the second treatment.

“I got home and ordered a wheelchair, a shower seat, a walker,” she said. “I am 35 years old and I have a wheelchair, a shower seat, a walker.” Just a few years ago she had run a marathon.

“My husband was helping me take a shower,” Ms. Lanoux said. “Of course it was awful. You’re cold, you can’t get enough water on you. I told him I don’t want to do this again. Call Dr. Hwu. I’m not going back.”

But she relented. Now Dr. Hwu wants her to try an experimental drug that takes the brakes off the immune system and might allow her body to destroy her cancer.

But the drug has not been approved by the Food and Drug Administration and is not available. Dr. Hwu knows it can have serious side effects and may not help Ms. Lanoux. But some who took the drug defied the odds, living for years. Maybe Ms. Lanoux could be one of those survivors, Dr. Hwu thinks.

And how about surgery, he asked her last month. “You can live with half a lung,” he said. But she probably would have to have her entire lung removed, he learned. And a surgeon would also have to take out the tumors on her liver. It may not be feasible, Dr. Hwu said, but, he added, “It’s definitely something I’m thinking about.”

Dr. Hwu struggles with the grim statistics — 8 percent of patients like Ms. Lanoux survive five years. The median survival rate is one year.

“It’s hard to see most patients die,” Dr. Hwu said. “You look at patients and see yourself and your family. We have to keep focusing on making these treatments better.”

On Wednesday, Ms. Lanoux was admitted for her eighth cycle of biochemotherapy. Dr. Hwu was worried.

“I don’t think her body will tolerate many more cycles,” he said. Already he has had to reduce the doses of some of the drugs and eliminate others.

In the meantime, he makes calls nearly every day, trying to get the experimental drug for Ms. Lanoux.

“We’re on the front lines,” he said. “We need armor.”

“I need this drug, and I need to be able to offer it to her.”

A View From Both Sides

As a breast cancer nurse, Cindy Davis thought she knew what her patients were going through. Until she went through it herself.

The first time she had a mammogram, it found cancer. She was 43. But after a lumpectomy, radiation and hormonal treatment with the drug tamoxifen, she was cancer free. The statistics were with her. She had every reason to think the cancer would not come back.

And that helped because she had taken a nursing job in the breast cancer clinic at Anderson, working with many patients pretty much like her — their cancer had been caught early, they would be fine.

Then, last April, nine years after the diagnosis, her cancer came back in a pelvic bone.

“You never think it is going to happen to you,” Mrs. Davis said. “I look at the risk factors, and I have none of them. It’s like, ‘Wait — I did everything right.’ ”

“I did the denial thing, 100 percent,” she said. “And I was angry. No, no, it can’t be that. And I was in shock — you’ve got to be kidding.”

As a nurse, she knew all too well there is no cure for breast cancer that has spread beyond the breast. Two-thirds with advanced disease are dead within five years.

“When you know what I know, it’s very scary,” Mrs. Davis said.

Her chemotherapy began a few days after she learned that her cancer had spread.

“I was scared; I was very scared,” Mrs. Davis said. “I know all the possible things that can go wrong.”

To her surprise, it was uneventful. Three weeks later, she and her husband went on a cruise. Just before it was over, her hair fell out.

“I got out of the shower and started combing my hair and it was coming out,” she said. “I started crying. Everyone says, ‘It’s just hair. It will grow back.’ But as women, that’s a big thing to us.”

Devastated, she got a wig and, feeling very self-conscious, went back to work. She has been working ever since, taking most of the week off after each chemotherapy treatment to recover from nausea and overwhelming fatigue. So far she has had 17 treatments, with more to come.

She is a nurse by day in the fifth-floor breast cancer clinic, and a patient in the evening, going to the eighth floor for chemotherapy. There she sees many of the women who were in the clinic earlier.

“It’s like a club,” Mrs. Davis said. The women talk about side effects — mouth sores and damage to the nerves of their feet — and the nausea and the anticipatory nausea.

“I have patients who say, ‘I just see a hospital gown and I feel nauseated,’ ” Mrs. Davis said. “I didn’t understand it before.”

She also asks patients for help, turning to those who learned they had advanced breast cancer two, three, four years ago.

“I say, ‘How do you do it?’ ” Mrs. Davis said. “They say they pray a lot and they just do it. They get through it one day at a time.”

Working at Anderson while being a patient there means cancer is always on her mind.

“You are around it all the time,” she said. “It’s just so hard to shut it off when you go home. Now I find myself thinking more and more about patients. I pray for them, and they hug me and say they are praying for me.”

She ran into a patient’s mother recently. The patient, a young woman, had advanced breast cancer and was terrified. Mrs. Davis told her she had advanced breast cancer, too, and she would help. “I am your nurse,” she told the young woman.

The mother came up to Mrs. Davis and said: “You have no idea how you have impacted this family. You gave my daughter hope that she could get through this.”

An Opponent That Won’t Quit

Dr. Raber used to think he understood when his patients told him that their appetite was good or that they were feeling more energetic.

But now, a cancer patient himself, he talks to patients in a very different way.

In the old days, if a patient said she had a good appetite, he would interpret that to mean her appetite was the same as his. Now he asks different questions.

“What did you have for lunch?”

“Crackers and soup.”

“What did you have for dinner?”

“Crackers and soup.”

“What did you have for breakfast?”

“I don’t eat breakfast.”

“Patients who say their appetite is fine often are saying it is better than it was,” Dr. Raber said. “They are not saying it is anything like the appetite of a healthy person.”

The same goes for energy level.

“When I came home from the hospital when I had been really, really sick, I was able to walk down the stairs once a day and up the stairs once a day. After I had been home for a couple of weeks, I could walk up and down maybe twice. If a doctor had asked how was my energy level, I would say, ‘Great, much better,’ ” Dr. Raber said. “The doctor would assume it was the same energy level as his.”

Dr. Raber’s journey as a cancer patient began in 1996, when he was 48 and physician-in-chief at Anderson. “I was at the top of my game,” he said.

A routine exam showed abnormalities in liver function tests. He thought it was nothing, waited six weeks, and had the test again.

The results were still abnormal. His internist suggested a CT scan, but neither Dr. Raber nor his doctor was concerned.

While Dr. Raber was on the table, the radiologist came in and said, “You have a problem.” There was a mass near his liver.

“This is serious,” he thought. “I figured, ‘This is early November. I could be dead by Christmas.’ ”

His doctor scheduled a biopsy for later that day.

That afternoon, after the biopsy, the pathologist told Dr. Raber he thought it was melanoma.

“I said to myself, melanoma. I could be dead by Thanksgiving,” Dr. Raber said.

It turned out to be lymphoma, a tumor of the lymphoid cells of the immune system, which is easier to treat and even cure than liver cancer or melanoma.

But treatment, with chemotherapy and radiation, made it impossible for Dr. Raber to work full time. At best, he could manage a few hours a day. He was ill, he was tired, and, he said, “My brain was scrambled.”

He stepped down as physician-in-chief. He no longer saw patients.

Two years later the cancer was back, in the same place. Once again he had aggressive chemotherapy and radiation. Two years after that, his kidneys failed. He spent time in the intensive care unit.

He did not work for a year, spending most of his time on the sofa. His lower body filled with fluid. His 32-inch waist ballooned to 52 inches. His size 9 ½ foot became a 12. All he could wear was a sweatsuit and slippers.

Finally, he went back to work for an hour, two or three times a week. And he went back not as an administrator but as a doctor and a teacher, “an earlier iteration of myself.”

In February, he got another cancer, melanoma.

By now he has gotten used to living with cancer.

“It just becomes your life,” Dr. Raber said. “You come in, you have tests, you go home, you do your thing, you come back again for treatment.

“I tell patients, ‘It used to be that you had cancer, you got treated, you died or you were cured,’ ” he said. “Now, for most of us, it’s a chronic illness. It’s not a question of being psyched up: I will have this surgery and then I will be cured. The disease comes back.”

He works part time, seeing patients on Tuesday and Thursday mornings and spending a day a week working at a clinic in the county hospital.

“A common question people would ask is ‘Are you a better doctor since you’ve been sick?’ ” Dr. Raber said. “My first answer is that I thought I was a good doctor before. I was worried about being a worse doctor. Having lived through these biopsies and all these tests, would I be hesitant to order all these things patients need because I had experienced them and knew they were not pleasant?

“Then I realized I am not better, but I am a different doctor,” he said. “I talk to patients differently. I understand more of what their situation might be.

“My life was very different than it was before that day in the CT scanner,” Dr. Raber said. “It’s not the life I thought I would have. But my life is still really good.

“My son is fond of saying, ‘It is what it is.’ That’s true. This is my life. I enjoy it a lot. It works out well for me.”

As for winning the war on cancer, Dr. Raber, on the front lines, has his own thoughts. “We are making a lot of progress,” he noted.

But “are we there yet?” he asked.

“Not even close.”

CYP2D6 POLYMORPHISM

Clin Pharmacokinet. 2009;48(11):689-723. doi: 10.2165/11318030-000000000-00000.

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Zhou SF.

Discipline of Chinese Medicine, School of Health Sciences, RMIT University, Victoria, Australia. shufeng.zhou@rmit.edu.au

Cytochrome P450 (CYP) 2D6 is one of the most investigated CYPs in relation to genetic polymorphism, but accounts for only a small percentage of all hepatic CYPs (approximately 2-4%). There is a large interindividual variation in the enzyme activity of CYP2D6. The enzyme is largely non-inducible and metabolizes approximately 25% of current drugs. Typical substrates for CYP2D6 are largely lipophilic bases and include some antidepressants, antipsychotics, antiarrhythmics, antiemetics, beta-adrenoceptor antagonists (beta-blockers) and opioids. The CYP2D6 activity ranges considerably within a population and includes ultrarapid metabolizers (UMs), extensive metabolizers (EMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). There is a considerable variability in the CYP2D6 allele distribution among different ethnic groups, resulting in variable percentages of PMs, IMs, EMs and UMs in a given population. To date, 74 allelic variants and a series of subvariants of the CYP2D6 gene have been reported and the number of alleles is still growing. Among these are fully functional alleles, alleles with reduced function and null (non-functional) alleles, which convey a wide range of enzyme activity, from no activity to ultrarapid metabolism of substrates. As a consequence, drug adverse effects or lack of drug effect may occur if standard doses are applied. The alleles *10, *17, *36 and *41 give rise to substrate-dependent decreased activity. Null alleles of CYP2D6 do not encode a functional protein and there is no detectable residual enzymatic activity. It is clear that alleles *3, *4, *5, *6, *7, *8, *11, *12, *13, *14, *15, *16, *18, *19, *20, *21, *38, *40, *42, *44, *56 and *62 have no enzyme activity. They are responsible for the PM phenotype when present in homozygous or compound heterozygous constellations. These alleles are of clinical significance as they often cause altered drug clearance and drug response. Among the most important variants are CYP2D6*2, *3, *4, *5, *10, *17 and *41. On the other hand, the CYP2D6 gene is subject to copy number variations that are often associated with the UM phenotype. Marked decreases in drug concentrations have been observed in UMs with tramadol, venlafaxine, morphine, mirtazapine and metoprolol. The functional impact of CYP2D6 alleles may be substrate-dependent. For example, CYP2D6*17 is generally considered as an allele with reduced function, but it displays remarkable variability in its activity towards substrates such as dextromethorphan, risperidone, codeine and haloperidol. The clinical consequence of the CYP2D6 polymorphism can be either occurrence of adverse drug reactions or altered drug response. Drugs that are most affected by CYP2D6 polymorphisms are commonly those in which CYP2D6 represents a substantial metabolic pathway either in the activation to form active metabolites or clearance of the agent. For example, encainide metabolites are more potent than the parent drug and thus QRS prolongation is more apparent in EMs than in PMs. In contrast, propafenone is a more potent beta-blocker than its metabolites and the beta-blocking activity during propafenone therapy is more prominent in PMs than EMs, as the parent drug accumulates in PMs. Since flecainide is mainly eliminated through renal excretion, and both R- and S-flecainide possess equivalent potency for sodium channel inhibition, the CYP2D6 phenotype has a minor impact on the response to flecainide. Since the contribution of CYP2D6 is greater for metoprolol than for carvedilol, propranolol and timolol, a stronger gene-dose effect is seen with this beta-blocker, while such an effect is lesser or marginal in other beta-blockers. Concordant genotype-phenotype correlation provides a basis for predicting the phenotype based on genetic testing, which has the potential to achieve optimal pharmacotherapy. However, genotype testing for CYP2D6 is not routinely performed in clinical practice and there is uncertainty regarding genotype-phenotype, gene-concentration and gene-dose relationships. Further prospective studies on the clinical impact of CYP2D6-dependent metabolism of drugs are warranted in large cohorts of subjects.