Oncology. 2008 Oct 1;75(3-4):169-174. [Epub ahead of print] Related Articles, LinkOut
Gender Differences in Treatment Outcomes among Patients with Non-Small Cell Lung Cancer Given a Combination of Carboplatin and Paclitaxel.
Yamamoto H, Sekine I, Yamada K, Nokihara H, Yamamoto N, Kunitoh H, Ohe Y, Tamura T.
Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Objectives: It was the aim of this study to investigate gender differences in the outcomes of carboplatin and paclitaxel chemotherapy in patients with unresectable stage IIIB-IV non-small cell lung cancer (NSCLC). Methods: Gender, age, performance status, histology, hematological toxicity, tumor responses and survival parameters obtained retrospectively by medical chart review were analyzed. Results: A total of 227 patients (147 males and 80 females) were included. The median lowest leukocyte count was 2,900 (range 1,200-12,400)/mul in males and 2,200 (range 600-6,500)/mul in females (p < style="border-bottom: 1px dashed rgb(0, 102, 204); cursor: pointer;" class="yshortcuts" id="lw_1223403352_14">leukopenia was noted in 15% of male and in 39% of female patients (p < class="yshortcuts" id="lw_1223403352_15">response rate in evaluable patients was 39%. The median progression-free survival was 4.4 months for men and 5.3 months for women (p = 0.0081). After progression of the disease, gefitinib was administered in 64 (44%) male and 45 (56%) female patients, with a median treatment of 35 and 144 days, respectively. The median survival time was 11.9 months for men and 22.2 months for women (p < class="yshortcuts" id="lw_1223403352_16">response rates did not differ between the genders. Of note, hematological toxicity was more severe in female patients. Copyright © 2008 S. Karger AG, Basel.
Τρίτη 7 Οκτωβρίου 2008
SURVIVAL BETTER FOR WOMEN
NO USE OF IMATINIB IN GLIOMAS
J Clin Oncol. 2008 Oct 1;26(28):4659-65. Related Articles, LinkOut
Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.
Raymond E, Brandes AA, Dittrich C, Fumoleau P, Coudert B, Clement PM, Frenay M, Rampling R, Stupp R, Kros JM, Heinrich MC, Gorlia T, Lacombe D, van den Bent MJ; European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.
Service Inter Hospitalier de Cancérologie, Beaujon University Hospital, Clichy.
PURPOSE: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas. PATIENTS: AND METHODS: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment. RESULTS: A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found. CONCLUSION: In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.
BEVACIZUMAB IN OVARIAN CANCER
Gynecol Oncol. 2008 Sep 29.
Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer.
Richardson DL, Backes FJ, Seamon LG, Zanagnolo V, O'Malley DM, Cohn DE, Fowler JM, Copeland LJ.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA.
OBJECTIVE: To describe the response rate (RR), progression-free survival (PFS), and toxicity profile of combination gemcitabine, platinum, and bevacizumab (GPB) for the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: A chart review of all patients with recurrent EOC who were treated with D1, D15 GPB in a 28-day cycle at a single institution was performed. Standard doses were gemcitabine 1000 mg/m(2), cisplatin 30 mg/m(2) or carboplatin AUC 3, and bevacizumab 10 mg/kg. All patients were analyzed for toxicity. RR and PFS were assessed in all patients who received at least 2 cycles of GPB. RESULTS: Thirty-five patients were identified, and 33 received at least 2 cycles of GPB. The majority of patients (80%) were platinum sensitive. Patients received a median of 6 cycles of GPB (range 1-24). Sixteen patients (48%) had a complete response (CR), and 10 patients (30%) had a partial response (PR), for a total RR of 78%. An additional 5 patients (15%) had stable disease, and only 2 (6%) patients had progressive disease. The median overall PFS was 12 months (95% CI 7-15), with a median follow-up time of 10 months (2-22). Two patients (6%) had bowel perforations, and both survived. Hematologic toxicities were most common, with 29% and 14% of patients experiencing grade 3 or 4 neutropenia and thrombocytopenia respectively. CONCLUSIONS: The combination of GPB demonstrated excellent efficacy for the treatment of recurrent EOC. However, serious toxicities occurred, and the safety profile of this combination requires further study.
Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer.
Richardson DL, Backes FJ, Seamon LG, Zanagnolo V, O'Malley DM, Cohn DE, Fowler JM, Copeland LJ.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA.
OBJECTIVE: To describe the response rate (RR), progression-free survival (PFS), and toxicity profile of combination gemcitabine, platinum, and bevacizumab (GPB) for the treatment of recurrent epithelial ovarian cancer (EOC). METHODS: A chart review of all patients with recurrent EOC who were treated with D1, D15 GPB in a 28-day cycle at a single institution was performed. Standard doses were gemcitabine 1000 mg/m(2), cisplatin 30 mg/m(2) or carboplatin AUC 3, and bevacizumab 10 mg/kg. All patients were analyzed for toxicity. RR and PFS were assessed in all patients who received at least 2 cycles of GPB. RESULTS: Thirty-five patients were identified, and 33 received at least 2 cycles of GPB. The majority of patients (80%) were platinum sensitive. Patients received a median of 6 cycles of GPB (range 1-24). Sixteen patients (48%) had a complete response (CR), and 10 patients (30%) had a partial response (PR), for a total RR of 78%. An additional 5 patients (15%) had stable disease, and only 2 (6%) patients had progressive disease. The median overall PFS was 12 months (95% CI 7-15), with a median follow-up time of 10 months (2-22). Two patients (6%) had bowel perforations, and both survived. Hematologic toxicities were most common, with 29% and 14% of patients experiencing grade 3 or 4 neutropenia and thrombocytopenia respectively. CONCLUSIONS: The combination of GPB demonstrated excellent efficacy for the treatment of recurrent EOC. However, serious toxicities occurred, and the safety profile of this combination requires further study.
TUMOR SIZE IMPORTANT IN T1 NSCLC
Tumor Size Important Indicator for Survival in Lung Cancer
September 4, 2008 — Among patients with resected non–small-cell lung carcinoma (NSCLC), tumors over 15 mm in diameter are associated with an increased risk for mediastinal metastases and with shorter 5-year survival. This was found to be the case in all tumor, node, and metastasis (TNM) system categories, researchers report in the September issue of the Journal of Thoracic Oncology.
"We have shown that inside the T1, tumors below 15 mm in diameter have a different behavior regarding survival than tumors over 15 mm," lead author Silvia Quadrelli, MD, a staff physician at Hospital Británico de Buenos Aires, in Argentina, told Medscape Oncology in an interview. "In practical terms, it means that we are putting patients together who are essentially different. And it also means that our estimates of survival may be wrong. The current system of classification doesn't clearly differentiate between these groups.
"In our study, we found that patients with tumors below 15 mm had a 5-year survival of 95%," she added. "In the other group, the patients had the same stage and the same pN0, but their tumors were larger than 15 mm, and their 5-year survival was only 65%. That is a great deal of difference."
The TNM system has been internationally recognized as the standard for staging extension and has also undergone repeated revision during the past 30 years. The last revision was in 2002 and has remained unchanged since then. Although the TNM stage remains the most important prognostic factor for patients with resected NSCLC, research during the past few years has begun to more closely examine the influence of tumor size, even within the same stage.
The increasing availability of more accurate imaging methods has allowed for the detection of very small lesions, but tumor size is a factor that has not changed since the initial staging system of 1973, and the cutoff value of 3 cm is still in use to discriminate between T1 and T2 tumors, the authors note. There has been growing controversy over the impact of tumor size by itself, as an independent variable unrelated to stage. Subdividing stage I in terms of tumor size has been considered as a result of these discussions.
"We have shown that size matters," said Dr. Quadrelli, "And we may need to redefine the T factor. Discovering very small tumors, even smaller than those discussed in our paper, may perhaps be more important."
Impact of Tumor Size
In this study, Dr. Quadrelli and colleagues evaluated the impact of tumor size on survival rates among 400 patients with NSCLC who underwent pulmonary resection with a curative intention. The median follow-up time was 44.7 months.
Adenocarcinoma was the most common type of malignancy, observed in 61.2% (n=245) of patients, followed by squamous cell, noted in 92 patients (23%). In 85.2% of the cohort (n=341), surgery was considered a complete resection. The majority of patients in the study were either clinical stage IA or IB (70.8%), and during the follow-up period, recurrences were reported in 137 patients, with distant recurrence being the most common (99 patients, 72.3%).
The researchers found that in an analysis looking at pathologic stage, the 5-year survival for patients at stage IA was 85.9%. However, when patients with neoplastic hilar, mediastinal, or distant metastases (pN0M0) were eliminated from the analysis and it included only those who had undergone a complete resection, the difference in survival was significantly altered in terms of tumor size. Patients with pN0 tumors that were smaller that 15 mm in diameter had a 5-year survival rate of 95%, compared with 65% among patients with tumors larger than 16 mm.
Upon multivariate analysis, tumor size and the T factor had independent prognostic effects on overall survival, and univariate analysis for pN0 patients showed that factors such as age, sex, location of tumor, or adenocarcinoma histology did not significantly affect survival. However, survival was negatively affected when the T factor was higher and the tumor size was larger.
"Our data suggest that tumors over 15 mm are associated with an increased risk of mediastinal metastases and with shorter 5-year survival in all TNM categories," conclude the researchers. "Current TNM categories are not sufficiently discriminatory, and the T factor requires to be reevaluated in further revisions of the TNM classification."
J Thorac Oncol. 2008;3:989-993. Abstract
September 4, 2008 — Among patients with resected non–small-cell lung carcinoma (NSCLC), tumors over 15 mm in diameter are associated with an increased risk for mediastinal metastases and with shorter 5-year survival. This was found to be the case in all tumor, node, and metastasis (TNM) system categories, researchers report in the September issue of the Journal of Thoracic Oncology.
"We have shown that inside the T1, tumors below 15 mm in diameter have a different behavior regarding survival than tumors over 15 mm," lead author Silvia Quadrelli, MD, a staff physician at Hospital Británico de Buenos Aires, in Argentina, told Medscape Oncology in an interview. "In practical terms, it means that we are putting patients together who are essentially different. And it also means that our estimates of survival may be wrong. The current system of classification doesn't clearly differentiate between these groups.
"In our study, we found that patients with tumors below 15 mm had a 5-year survival of 95%," she added. "In the other group, the patients had the same stage and the same pN0, but their tumors were larger than 15 mm, and their 5-year survival was only 65%. That is a great deal of difference."
The TNM system has been internationally recognized as the standard for staging extension and has also undergone repeated revision during the past 30 years. The last revision was in 2002 and has remained unchanged since then. Although the TNM stage remains the most important prognostic factor for patients with resected NSCLC, research during the past few years has begun to more closely examine the influence of tumor size, even within the same stage.
The increasing availability of more accurate imaging methods has allowed for the detection of very small lesions, but tumor size is a factor that has not changed since the initial staging system of 1973, and the cutoff value of 3 cm is still in use to discriminate between T1 and T2 tumors, the authors note. There has been growing controversy over the impact of tumor size by itself, as an independent variable unrelated to stage. Subdividing stage I in terms of tumor size has been considered as a result of these discussions.
"We have shown that size matters," said Dr. Quadrelli, "And we may need to redefine the T factor. Discovering very small tumors, even smaller than those discussed in our paper, may perhaps be more important."
Impact of Tumor Size
In this study, Dr. Quadrelli and colleagues evaluated the impact of tumor size on survival rates among 400 patients with NSCLC who underwent pulmonary resection with a curative intention. The median follow-up time was 44.7 months.
Adenocarcinoma was the most common type of malignancy, observed in 61.2% (n=245) of patients, followed by squamous cell, noted in 92 patients (23%). In 85.2% of the cohort (n=341), surgery was considered a complete resection. The majority of patients in the study were either clinical stage IA or IB (70.8%), and during the follow-up period, recurrences were reported in 137 patients, with distant recurrence being the most common (99 patients, 72.3%).
The researchers found that in an analysis looking at pathologic stage, the 5-year survival for patients at stage IA was 85.9%. However, when patients with neoplastic hilar, mediastinal, or distant metastases (pN0M0) were eliminated from the analysis and it included only those who had undergone a complete resection, the difference in survival was significantly altered in terms of tumor size. Patients with pN0 tumors that were smaller that 15 mm in diameter had a 5-year survival rate of 95%, compared with 65% among patients with tumors larger than 16 mm.
Upon multivariate analysis, tumor size and the T factor had independent prognostic effects on overall survival, and univariate analysis for pN0 patients showed that factors such as age, sex, location of tumor, or adenocarcinoma histology did not significantly affect survival. However, survival was negatively affected when the T factor was higher and the tumor size was larger.
"Our data suggest that tumors over 15 mm are associated with an increased risk of mediastinal metastases and with shorter 5-year survival in all TNM categories," conclude the researchers. "Current TNM categories are not sufficiently discriminatory, and the T factor requires to be reevaluated in further revisions of the TNM classification."
J Thorac Oncol. 2008;3:989-993. Abstract
Κυριακή 5 Οκτωβρίου 2008
RALOXIFENE AND ENDOMETRIAL CANCER
Raloxifene Reduces Risk of Endometrial Cancer
NEW YORK (Reuters Health) Sept 25 - While raloxifene and tamoxifen are broadly similar in reducing breast cancer risk, raloxifene also appears to lower the odds of developing endometrial cancer, researchers report in the September 1st issue of the Journal of Clinical Oncology.
"These data are important," lead investigator Dr. Angela DeMichele told Reuters Health, "because they suggest a critical difference between tamoxifen and raloxifene that could help physicians in tailoring therapy to the patient."
She added, "A randomized clinical trial has shown that the drugs are roughly equivalent in terms of their ability to prevent breast cancer."
To examine the effect of raloxifene and tamoxifen on endometrial cancer risk, Dr. DeMichele of the University of Pennsylvania, Philadelphia, and colleagues examined data on 547 women who were diagnosed with endometrial cancer and 1410 controls.
Some 3.3% of the cases had taken raloxifene compared to 6.6% of the controls. Corresponding proportions for tamoxifen were 6.2% and 2.4%.
After adjustment for other risk factors, the risk of endometrial cancer in raloxifene users was half that of nonusers (odds ratio = 0.50). Tamoxifen users were three times more likely to develop endometrial cancer than were raloxifene users (odds ratio = 3.0).
Overall, raloxifene users were at significantly reduced risk of endometrial cancer compared to both tamoxifen users and women who did not use a selective estrogen receptor modulator.
Given the similarity in protection against breast cancer, continued Dr. DeMichele, "a secondary benefit, like a reduction in the risk of endometrial cancer, may be very important to patients who have not had a hysterectomy and are concerned about the increased risk of endometrial cancer with tamoxifen."
J Clin Oncol 2008;26:4151-4159.
NEW YORK (Reuters Health) Sept 25 - While raloxifene and tamoxifen are broadly similar in reducing breast cancer risk, raloxifene also appears to lower the odds of developing endometrial cancer, researchers report in the September 1st issue of the Journal of Clinical Oncology.
"These data are important," lead investigator Dr. Angela DeMichele told Reuters Health, "because they suggest a critical difference between tamoxifen and raloxifene that could help physicians in tailoring therapy to the patient."
She added, "A randomized clinical trial has shown that the drugs are roughly equivalent in terms of their ability to prevent breast cancer."
To examine the effect of raloxifene and tamoxifen on endometrial cancer risk, Dr. DeMichele of the University of Pennsylvania, Philadelphia, and colleagues examined data on 547 women who were diagnosed with endometrial cancer and 1410 controls.
Some 3.3% of the cases had taken raloxifene compared to 6.6% of the controls. Corresponding proportions for tamoxifen were 6.2% and 2.4%.
After adjustment for other risk factors, the risk of endometrial cancer in raloxifene users was half that of nonusers (odds ratio = 0.50). Tamoxifen users were three times more likely to develop endometrial cancer than were raloxifene users (odds ratio = 3.0).
Overall, raloxifene users were at significantly reduced risk of endometrial cancer compared to both tamoxifen users and women who did not use a selective estrogen receptor modulator.
Given the similarity in protection against breast cancer, continued Dr. DeMichele, "a secondary benefit, like a reduction in the risk of endometrial cancer, may be very important to patients who have not had a hysterectomy and are concerned about the increased risk of endometrial cancer with tamoxifen."
J Clin Oncol 2008;26:4151-4159.
UP TO 4.5 HOURS THROMBOLYSIS BENEFICIAL FOR ISCHEMIC STROKES
ECASS 3 Gets a Warm Welcome From the Stroke Community
October 2, 2008 (Vienna, Austria) — Results of the third European Cooperative Acute Stroke Study (ECASS 3) were met with prolonged applause and general enthusiasm from stroke experts here at the 6th World Stroke Congress. The findings are expected by many to change the treatment of acute ischemic stroke, providing reassurance even for skeptics that treating patients with tissue plasminogen activator (tPA) up to 4.5 hours is safe and effective.
The trial compared treatment with tPA in the 3-to-4.5-hour window after a stroke with no treatment. To date, tPA is approved for use only up to 3 hours after the onset of symptoms. Results showed treatment in the extended window can still provide "modest but significant" benefit to patients, investigators reported. Although symptomatic intracerebral hemorrhage was higher in treated patients, the rate was not higher than reported previously among patients treated within the currently approved 3-hour window and was not associated with increased mortality.
Werner Hacke, MD, from the University of Heidelberg, in Germany, principal investigator of the ECASS 3 trial, presented the findings here on behalf of the trialists. He emphasized that although these findings "open the window" for patients who arrive later than the 3-hour time limit, the goal of therapy still must be to treat as soon as possible, since efficacy begins to decline after only 90 minutes from symptom onset.
"There may be more time for patients who cannot get in earlier, but there is no more time for physicians," he said. "They have to speed up even more."
The findings were published in the September 25 issue of the New England Journal of Medicine and were presented here the same day, although the embargo was lifted by the Journal the evening before. The study was supported by Boehringer Ingelheim.
During a press conference, Dr. Hacke said the new results will be considered in the next 6-month review of the European stroke guidelines in November and that it is "highly likely" that the sponsor will apply for regulatory approval of the additional indication.
A "Tremendous Advance"
These findings represent a "tremendous advance," said Vladimir Hachinski, MD, professor of neurology at the University of Western Ontario, in London, and editor-in-chief of the American Heart Association journal Stroke. "It tells us that not only do we have the 3 hours, but we can go beyond, and I think because we have a second study that thrombolysis works, this will convince a number of skeptics that it's a good drug."
I think it's a tremendous advance, because it tells us that not only do we have the 3 hours, but we can go beyond.
At the same time, though, he noted that people should remember another good "treatment" for stroke, organized stroke units, that help patients of all ages and types, whether they are candidates for thrombolysis or not. "I'm not talking about 1 or the other; I'm talking about doing the simple things and then adding this now-extended time window of opportunity to make a difference in stroke," Dr. Hachinski said. "It is so disabling a disease that even a small difference in the outcome of patients makes a big difference in the long term, so I think this is terrific."
Still, Dr. Hachinski said he sees a "big educational challenge" in getting doctors, especially those in specialties other than neurology, to use the drug, because they are frankly "terrified."
"Let's be fair. It's a powerful drug and has powerful side effects," he said. "It's a balance of good vs potential side effects. I think the balance is clearly in favor of doing it, but obviously each case has to be treated individually, and I think there's a risk there. But the risk of not giving it is greater than the risk of giving it, on balance."
Philip Gorelick, MD, John S. Garvin Professor and head of the department of neurology and rehabilitation at the University of Illinois College of Medicine at Chicago and recent chair of the American Heart Association International Stroke Conference, said Dr. Hacke and colleagues are to be congratulated on completing a complex and large-scale trial. "The study has generated good news for stroke patients and for vascular neurologists and other physicians who treat acute ischemic stroke patients, and it will likely influence future acute ischemic stroke treatment guidelines, although in patients with less severe stroke deficits in the extended time window," Dr. Gorelick told Medscape Neurology & Neurosurgery.
A key to using the treatment in this setting will be to minimize hemorrhagic risk, he noted. "It will be interesting to learn of exploratory data from the study regarding predictors of hemorrhage and furthermore to understand information about the distribution of stroke subtypes in the study and response to treatment by stroke subtype," Dr. Gorelick added. "These additional sources of information may help practicing clinicians better apply alteplase in the extended time window, if approved for this indication by major regulatory bodies."
The current study with a 3-to-4.5-hour time window should not be taken as a prescription to delay treatment.
Perfusion/diffusion magnetic resonance imaging (MRI) may play a future role in selecting which patients can be treated in the 3-to-4.5-hour window or even up to 6 hours, he added, based on exploratory findings from the previously published Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and other studies.
Early treatment, however, remains the goal, he emphasized. "The current study with a 3-to-4.5-hour window should not be taken as a prescription to delay treatment of acute ischemic stroke if intravenous [IV] thrombolytic therapy can be administered sooner."
More Patients Treated in 3-Hour Window?
Ralph Sacco, MD, from the Miller School of Medicine at the University of Miami, in Florida, called the data "impressive" but said a change in practice should await, first, review of the findings by the American Heart Association/American Stroke Association guidelines committee and, second, approval of the new indication by the Food and Drug Administration (FDA), if the company chooses to seek it.
Faster treatment is better, of course, he said, but this information will provide some flexibility. "It used to be if somebody came in at, say, 2 hours and 20 minutes, it was tough to get everything done and get them treated in within 3 hours," Dr. Sacco told Medscape Neurology & Neurosurgery. "Now, if somebody comes in within 3 hours, I think it will be very reasonable to get them treated, should the guidelines change, and should the FDA approve it, within 4.5 hours.
"I think it's exciting for stroke, it's hopeful for the many stroke patients we treat, and it's uplifting to get another positive trial," he said.
But Will Patients Be Treated Later?
Joseph Broderick, MD, from the University of Cincinnati, in Ohio, and a primary investigator of the National Institute of Neurological Disorders and Stroke (NINDS) trial that first established efficacy of tPA in stroke, told Medscape Neurology & Neurosurgery that, in his view, the ECASS 3 results are the most important to the field of stroke treatment since the NINDS results were published some 13 years ago.
However, like the ECASS 3 researchers and others, he too is concerned that physicians will take more time if they think they have it. "Unfortunately with physicians, sometimes the more time you have, the more you kind of drag your feet or you want to do another test, and what I worry about is that people will be treated later when it's clear that this is a very time-dependent therapy."
What I worry about is that people will be treated later, and it's clear that this is a very time-dependent therapy.
He said the efficacy in ECASS 3 was similar to that seen in the NINDS trial, although he noted that the ECASS 3 population was a much less severely affected group. "I think their median [National Institutes of Health Stroke Scale] NIHSS score was 9 to 10 as opposed to 14 in the NINDS trial, which is a big difference," he said. "That's why their mortality is extraordinarily low, around 8%, whereas in the [NINDS] trial, the mortality with placebo was 21% and with tPA it was 17%, so you're talking about half the mortality rate, but that reflects the lesser severity of the strokes."
The findings, then, do not provide information on the patients excluded from the trial, Dr. Broderick said. Still, he added, "It's just a great event that builds upon the positive momentum. I still think reperfusion is what it's all about, but reperfusion within a certain time window."
During his presentation, Dr. Hacke acknowledged this limitation for the generalizability of their results but pointed out that the inclusion criteria for the ECASS 3 study were identical to the labeling of tPA for Europe, except for the time window. "So we were not responsible as the investigators that the age limit ended at 80. We were also not responsible that there was exclusion of patients who had had a prior stroke and were diabetic, but that's what we had to do."
Dr. Mark Alberts (Source: Northwestern Medical Faculty Foundation)
Dr. Mark Alberts (Source: Northwestern Medical Faculty Foundation)
Mark Alberts, MD, from Northwestern University Medical School, in Chicago, Illinois, said he feels that 1 of the "main victories" of ECASS 3 is the expansion of the time window for IV tPA, making more patients eligible for this therapy. "It also confirms the effectiveness and safety of IV tPA, which has been questioned by a vocal minority of emergency department physicians," he said.
"What I think the challenge is going to be, when and if we rewrite the acute stroke guidelines, is what are we going to say about ECASS 3?" Dr. Alberts said, referring to this difference in populations between the NINDS and ECASS 3 trials. "Are we just going to change the time window for IV tPA to 4.5 hours or make it 1 set of guidelines for patients within 3 hours and another set of guidelines for patients between 3 and 4.5 hours?"
When and if we rewrite the acute stroke guidelines, what are we going to say about ECASS 3?
Dr. Broderick raised essentially this same question to Dr. Hacke during the session, pointing out that the NINDS trial did show a benefit among these older patients with more severe strokes, but only out to 3 hours. Dr. Hacke responded that in clinical practice, doctors have to make decisions based on individual cases but said that he feels that any change to evidence-based guidelines for the 3-to-4.5-hour window would have to reflect the boundaries of the ECASS 3 trial, including the upper age and stroke-severity limits. "In the text, we should be able expound on that, and that finally would be an individual decision to be discussed with the patient and the relatives," he added.
Implications for Ongoing Trials?
Finally, Dr. Broderick pointed out that these findings are going to affect a lot of ongoing trials that are scrambling right now to evaluate what the implications are. "Think about all the trials that are ongoing right now that sort of cede the 3-hour window, saying up to 3 hours we have tPA but after 3 hours, we're using imaging to decide whether or not we should select patients, we're doing device studies," he told Medscape Neurology & Neurosurgery. "Well, all of a sudden, we're going to have an effective treatment that's now maybe going out to 4.5 hours, so all those trials are going to have to reconsider."
Dr. Broderick is directing the Interventional Management of Stroke (IMS) 3 trial, for example, an NIH-funded study looking at IV tPA full dose vs two-thirds of the dose followed by endovascular therapy, with 200 patients already randomized. "But we've got a 3-hour time window. Does that mean now that we have to go to 4.5 because the tPA treatment window is going to be moved out? We're going to have to think very hard about that, because it changes our study design, and maybe the effect we expect to see."
We're going to have to think very hard about that because it changes our study design, and maybe the effect we expect to see.
Asked about this latter point, Dr. Hacke told Medscape Neurology & Neurosurgery that he had already been approached by a number of investigators with this concern. However, he noted, "until the change in labeling has occurred, there is no legal necessity to do it. We know for sure it works, but it will still be off label until the FDA and the [European Medicines Agency] EMEA and other worldwide institutions have approved the prolonged window. Therefore, any trial that is going on right now can continue, even if they start at 3 hours," he said.
Most centers that participate in clinical trials are highly experienced and will in most countries take the initiative to treat off label, he noted, so he expects many will probably stop randomizing these patients, although they won't be compelled to do so until a new indication for the 3-to-4.5-hour window is approved. "But that will be a period of 2 years, as I learned yesterday," Dr. Hacke added. "Two years." During that time in Europe, he said, thousands of patients will not get the benefit of this therapy.
At least, he said, he is hopeful that the data showing efficacy and safety out to 4.5 hours will provide some confidence to those who had been reluctant to use tPA even within the approved 3-hour window.
Continuing Uncertainty
During the discussion period after the presentation, Peter Sandercock, MD, professor of medical neurology at Western General Hospital, in Edinburgh, Scotland, and co–principal investigator of the ongoing International Stroke Trial 3 (IST 3), said that it is acceptable to continue to randomize patients where there is continuing uncertainty.
"As Werner rightfully emphasized, there are a number of people who are excluded even with the ECASS 3 results," Dr. Sandercock told the meeting here. "These are patients over 80, patients with a prior stroke and history of diabetes, and patients with an NIHSS score of more than 25, and these are areas where we now need randomized scientific evidence. The IST 3 data monitoring committee decided on Tuesday night to continue randomizing patients in the trial to gain important information on whether we can extend treatment even further than the ECASS 3 data suggest is important."
Jim Grotta, MD, from the University of Texas Medical School at Houston, pointed out that the ECASS 3 results appear to exactly replicate what was expected from the pooled analysis of previous randomized trials. "One of the beautiful things about how you designed the trial is that it enables us to pool your data with the existing pooled data," he told Dr. Hacke. Some of these continuing questions such as the effect in older patients could perhaps be answered by pooling the data, Dr. Grotta noted, "so I hope the pooling group will get together fast."
Heady Success
At the meeting here, the heady effect of a positive result in a stroke trial — only the second such result with any pharmacologic therapy after the NINDS trial in 1995 — was tangible in the audience.
At the close of Dr. Hacke's presentation and the prolonged spontaneous applause that followed, Stephen Davis, MD, from the Royal Melbourne Hospital at the University of Melbourne, in Victoria, Australia and comoderator of the session, who was not involved in the study, was effusive.
"I want to warmly congratulate you, the steering committees, the other committees, the sponsor, and the investigators of this landmark study, ECASS 3, this highly successful study that I believe will lead to a change in clinical practice and guidelines and allow the extension of the time window to 4.5 hours with tPA, certainly supported by the meta-analysis and safety data from [the Safe Implementation of Thrombolysis in Stroke Monitoring Study] SITS-MOST," Dr. Davis said. "I think this will also increase the number of patients treated within 3 hours — bearing in mind your comments that no time should be wasted — as well as up to 4.5 hours."
Patrick Lyden, MD, from the University of California, San Diego, and an NINDS trial investigator, wrote the editorial that accompanied the publication of the trial results in the New England Journal of Medicine. During the discussion, he said he had had more time perhaps than some others to reflect on what the importance of this trial might be. Although there are some issues that Dr. Hacke and others have pointed out, Dr. Lyden acknowledged, "I think it's very important that we not spend time on minor issues and think about the bigger picture. There should be no more doubt in anyone's mind that intravenous thrombolytic therapy is an effective treatment.
"It's time to stop taking patients to places where either there's reluctance or lack of skill or lack of capacity to give the therapy," he concluded, prompting another burst of applause.
Not Everyone Convinced?
Among the final questions was 1 on whether, in places where intra-arterial thrombolysis was available, Dr. Hacke would use that approach first before intravenous tPA after 3 hours. The question underlines a controversial move by some in the community to use interventional treatments preferentially for the treatment of stroke.
It's time to stop taking patients to places where either there's reluctance or lack of skill or lack of capacity to give the therapy.
Dr. Hacke is not among these. Until 3 hours after symptom onset, intravenous tPA is the approved treatment, he said. "In my opinion, there is no good reason, unless you identify a very peculiar situation in a given patient, like a basilar artery occlusion or a carotid T occlusion, to use any intra-arterial device in the presence of an established medical treatment, a medical treatment that yields recanalization rates on the order of 40% to 50% and that has controlled outcome data that are far better than the outcome data that come from uncontrolled, and let me frankly say, lousy case series," he replied bluntly.
That will also be true soon out to 4.5 hours, he added. If the patient is not responding and it becomes clear that there is a tight stenosis of the middle cerebral artery, for example, then an individual decision can be made to use additional rescue therapies, he said.
"But I strongly disagree with any notion that there should be a priority for intra-arterial therapy," Dr. Hacke said. He called on the interventional community to undertake clinical trials to prove the efficacy of these therapies. "And I say that as someone who started with interventional therapies while those colleagues were still in school."
At the end of the session, the moderators called for a show of hands on who, given the ECASS 3 data, would treat a patient showing up at 4 hours after symptom onset with thrombolytic therapy. Dr. Davis called the result a "sizable majority," in favor of treatment, but still, it did not include everyone.
"Can we see who would not?" Dr. Hacke quipped. "So we know where not to go."
N Engl J Med. 2008;359:1317-1329 Abstract, 1393-1395. Abstract
6th World Stroke Congress, Vienna, Austria: Abstract OR06-05. Presented September 25, 2008.
October 2, 2008 (Vienna, Austria) — Results of the third European Cooperative Acute Stroke Study (ECASS 3) were met with prolonged applause and general enthusiasm from stroke experts here at the 6th World Stroke Congress. The findings are expected by many to change the treatment of acute ischemic stroke, providing reassurance even for skeptics that treating patients with tissue plasminogen activator (tPA) up to 4.5 hours is safe and effective.
The trial compared treatment with tPA in the 3-to-4.5-hour window after a stroke with no treatment. To date, tPA is approved for use only up to 3 hours after the onset of symptoms. Results showed treatment in the extended window can still provide "modest but significant" benefit to patients, investigators reported. Although symptomatic intracerebral hemorrhage was higher in treated patients, the rate was not higher than reported previously among patients treated within the currently approved 3-hour window and was not associated with increased mortality.
Werner Hacke, MD, from the University of Heidelberg, in Germany, principal investigator of the ECASS 3 trial, presented the findings here on behalf of the trialists. He emphasized that although these findings "open the window" for patients who arrive later than the 3-hour time limit, the goal of therapy still must be to treat as soon as possible, since efficacy begins to decline after only 90 minutes from symptom onset.
"There may be more time for patients who cannot get in earlier, but there is no more time for physicians," he said. "They have to speed up even more."
The findings were published in the September 25 issue of the New England Journal of Medicine and were presented here the same day, although the embargo was lifted by the Journal the evening before. The study was supported by Boehringer Ingelheim.
During a press conference, Dr. Hacke said the new results will be considered in the next 6-month review of the European stroke guidelines in November and that it is "highly likely" that the sponsor will apply for regulatory approval of the additional indication.
A "Tremendous Advance"
These findings represent a "tremendous advance," said Vladimir Hachinski, MD, professor of neurology at the University of Western Ontario, in London, and editor-in-chief of the American Heart Association journal Stroke. "It tells us that not only do we have the 3 hours, but we can go beyond, and I think because we have a second study that thrombolysis works, this will convince a number of skeptics that it's a good drug."
I think it's a tremendous advance, because it tells us that not only do we have the 3 hours, but we can go beyond.
At the same time, though, he noted that people should remember another good "treatment" for stroke, organized stroke units, that help patients of all ages and types, whether they are candidates for thrombolysis or not. "I'm not talking about 1 or the other; I'm talking about doing the simple things and then adding this now-extended time window of opportunity to make a difference in stroke," Dr. Hachinski said. "It is so disabling a disease that even a small difference in the outcome of patients makes a big difference in the long term, so I think this is terrific."
Still, Dr. Hachinski said he sees a "big educational challenge" in getting doctors, especially those in specialties other than neurology, to use the drug, because they are frankly "terrified."
"Let's be fair. It's a powerful drug and has powerful side effects," he said. "It's a balance of good vs potential side effects. I think the balance is clearly in favor of doing it, but obviously each case has to be treated individually, and I think there's a risk there. But the risk of not giving it is greater than the risk of giving it, on balance."
Philip Gorelick, MD, John S. Garvin Professor and head of the department of neurology and rehabilitation at the University of Illinois College of Medicine at Chicago and recent chair of the American Heart Association International Stroke Conference, said Dr. Hacke and colleagues are to be congratulated on completing a complex and large-scale trial. "The study has generated good news for stroke patients and for vascular neurologists and other physicians who treat acute ischemic stroke patients, and it will likely influence future acute ischemic stroke treatment guidelines, although in patients with less severe stroke deficits in the extended time window," Dr. Gorelick told Medscape Neurology & Neurosurgery.
A key to using the treatment in this setting will be to minimize hemorrhagic risk, he noted. "It will be interesting to learn of exploratory data from the study regarding predictors of hemorrhage and furthermore to understand information about the distribution of stroke subtypes in the study and response to treatment by stroke subtype," Dr. Gorelick added. "These additional sources of information may help practicing clinicians better apply alteplase in the extended time window, if approved for this indication by major regulatory bodies."
The current study with a 3-to-4.5-hour time window should not be taken as a prescription to delay treatment.
Perfusion/diffusion magnetic resonance imaging (MRI) may play a future role in selecting which patients can be treated in the 3-to-4.5-hour window or even up to 6 hours, he added, based on exploratory findings from the previously published Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and other studies.
Early treatment, however, remains the goal, he emphasized. "The current study with a 3-to-4.5-hour window should not be taken as a prescription to delay treatment of acute ischemic stroke if intravenous [IV] thrombolytic therapy can be administered sooner."
More Patients Treated in 3-Hour Window?
Ralph Sacco, MD, from the Miller School of Medicine at the University of Miami, in Florida, called the data "impressive" but said a change in practice should await, first, review of the findings by the American Heart Association/American Stroke Association guidelines committee and, second, approval of the new indication by the Food and Drug Administration (FDA), if the company chooses to seek it.
Faster treatment is better, of course, he said, but this information will provide some flexibility. "It used to be if somebody came in at, say, 2 hours and 20 minutes, it was tough to get everything done and get them treated in within 3 hours," Dr. Sacco told Medscape Neurology & Neurosurgery. "Now, if somebody comes in within 3 hours, I think it will be very reasonable to get them treated, should the guidelines change, and should the FDA approve it, within 4.5 hours.
"I think it's exciting for stroke, it's hopeful for the many stroke patients we treat, and it's uplifting to get another positive trial," he said.
But Will Patients Be Treated Later?
Joseph Broderick, MD, from the University of Cincinnati, in Ohio, and a primary investigator of the National Institute of Neurological Disorders and Stroke (NINDS) trial that first established efficacy of tPA in stroke, told Medscape Neurology & Neurosurgery that, in his view, the ECASS 3 results are the most important to the field of stroke treatment since the NINDS results were published some 13 years ago.
However, like the ECASS 3 researchers and others, he too is concerned that physicians will take more time if they think they have it. "Unfortunately with physicians, sometimes the more time you have, the more you kind of drag your feet or you want to do another test, and what I worry about is that people will be treated later when it's clear that this is a very time-dependent therapy."
What I worry about is that people will be treated later, and it's clear that this is a very time-dependent therapy.
He said the efficacy in ECASS 3 was similar to that seen in the NINDS trial, although he noted that the ECASS 3 population was a much less severely affected group. "I think their median [National Institutes of Health Stroke Scale] NIHSS score was 9 to 10 as opposed to 14 in the NINDS trial, which is a big difference," he said. "That's why their mortality is extraordinarily low, around 8%, whereas in the [NINDS] trial, the mortality with placebo was 21% and with tPA it was 17%, so you're talking about half the mortality rate, but that reflects the lesser severity of the strokes."
The findings, then, do not provide information on the patients excluded from the trial, Dr. Broderick said. Still, he added, "It's just a great event that builds upon the positive momentum. I still think reperfusion is what it's all about, but reperfusion within a certain time window."
During his presentation, Dr. Hacke acknowledged this limitation for the generalizability of their results but pointed out that the inclusion criteria for the ECASS 3 study were identical to the labeling of tPA for Europe, except for the time window. "So we were not responsible as the investigators that the age limit ended at 80. We were also not responsible that there was exclusion of patients who had had a prior stroke and were diabetic, but that's what we had to do."
Dr. Mark Alberts (Source: Northwestern Medical Faculty Foundation)
Dr. Mark Alberts (Source: Northwestern Medical Faculty Foundation)
Mark Alberts, MD, from Northwestern University Medical School, in Chicago, Illinois, said he feels that 1 of the "main victories" of ECASS 3 is the expansion of the time window for IV tPA, making more patients eligible for this therapy. "It also confirms the effectiveness and safety of IV tPA, which has been questioned by a vocal minority of emergency department physicians," he said.
"What I think the challenge is going to be, when and if we rewrite the acute stroke guidelines, is what are we going to say about ECASS 3?" Dr. Alberts said, referring to this difference in populations between the NINDS and ECASS 3 trials. "Are we just going to change the time window for IV tPA to 4.5 hours or make it 1 set of guidelines for patients within 3 hours and another set of guidelines for patients between 3 and 4.5 hours?"
When and if we rewrite the acute stroke guidelines, what are we going to say about ECASS 3?
Dr. Broderick raised essentially this same question to Dr. Hacke during the session, pointing out that the NINDS trial did show a benefit among these older patients with more severe strokes, but only out to 3 hours. Dr. Hacke responded that in clinical practice, doctors have to make decisions based on individual cases but said that he feels that any change to evidence-based guidelines for the 3-to-4.5-hour window would have to reflect the boundaries of the ECASS 3 trial, including the upper age and stroke-severity limits. "In the text, we should be able expound on that, and that finally would be an individual decision to be discussed with the patient and the relatives," he added.
Implications for Ongoing Trials?
Finally, Dr. Broderick pointed out that these findings are going to affect a lot of ongoing trials that are scrambling right now to evaluate what the implications are. "Think about all the trials that are ongoing right now that sort of cede the 3-hour window, saying up to 3 hours we have tPA but after 3 hours, we're using imaging to decide whether or not we should select patients, we're doing device studies," he told Medscape Neurology & Neurosurgery. "Well, all of a sudden, we're going to have an effective treatment that's now maybe going out to 4.5 hours, so all those trials are going to have to reconsider."
Dr. Broderick is directing the Interventional Management of Stroke (IMS) 3 trial, for example, an NIH-funded study looking at IV tPA full dose vs two-thirds of the dose followed by endovascular therapy, with 200 patients already randomized. "But we've got a 3-hour time window. Does that mean now that we have to go to 4.5 because the tPA treatment window is going to be moved out? We're going to have to think very hard about that, because it changes our study design, and maybe the effect we expect to see."
We're going to have to think very hard about that because it changes our study design, and maybe the effect we expect to see.
Asked about this latter point, Dr. Hacke told Medscape Neurology & Neurosurgery that he had already been approached by a number of investigators with this concern. However, he noted, "until the change in labeling has occurred, there is no legal necessity to do it. We know for sure it works, but it will still be off label until the FDA and the [European Medicines Agency] EMEA and other worldwide institutions have approved the prolonged window. Therefore, any trial that is going on right now can continue, even if they start at 3 hours," he said.
Most centers that participate in clinical trials are highly experienced and will in most countries take the initiative to treat off label, he noted, so he expects many will probably stop randomizing these patients, although they won't be compelled to do so until a new indication for the 3-to-4.5-hour window is approved. "But that will be a period of 2 years, as I learned yesterday," Dr. Hacke added. "Two years." During that time in Europe, he said, thousands of patients will not get the benefit of this therapy.
At least, he said, he is hopeful that the data showing efficacy and safety out to 4.5 hours will provide some confidence to those who had been reluctant to use tPA even within the approved 3-hour window.
Continuing Uncertainty
During the discussion period after the presentation, Peter Sandercock, MD, professor of medical neurology at Western General Hospital, in Edinburgh, Scotland, and co–principal investigator of the ongoing International Stroke Trial 3 (IST 3), said that it is acceptable to continue to randomize patients where there is continuing uncertainty.
"As Werner rightfully emphasized, there are a number of people who are excluded even with the ECASS 3 results," Dr. Sandercock told the meeting here. "These are patients over 80, patients with a prior stroke and history of diabetes, and patients with an NIHSS score of more than 25, and these are areas where we now need randomized scientific evidence. The IST 3 data monitoring committee decided on Tuesday night to continue randomizing patients in the trial to gain important information on whether we can extend treatment even further than the ECASS 3 data suggest is important."
Jim Grotta, MD, from the University of Texas Medical School at Houston, pointed out that the ECASS 3 results appear to exactly replicate what was expected from the pooled analysis of previous randomized trials. "One of the beautiful things about how you designed the trial is that it enables us to pool your data with the existing pooled data," he told Dr. Hacke. Some of these continuing questions such as the effect in older patients could perhaps be answered by pooling the data, Dr. Grotta noted, "so I hope the pooling group will get together fast."
Heady Success
At the meeting here, the heady effect of a positive result in a stroke trial — only the second such result with any pharmacologic therapy after the NINDS trial in 1995 — was tangible in the audience.
At the close of Dr. Hacke's presentation and the prolonged spontaneous applause that followed, Stephen Davis, MD, from the Royal Melbourne Hospital at the University of Melbourne, in Victoria, Australia and comoderator of the session, who was not involved in the study, was effusive.
"I want to warmly congratulate you, the steering committees, the other committees, the sponsor, and the investigators of this landmark study, ECASS 3, this highly successful study that I believe will lead to a change in clinical practice and guidelines and allow the extension of the time window to 4.5 hours with tPA, certainly supported by the meta-analysis and safety data from [the Safe Implementation of Thrombolysis in Stroke Monitoring Study] SITS-MOST," Dr. Davis said. "I think this will also increase the number of patients treated within 3 hours — bearing in mind your comments that no time should be wasted — as well as up to 4.5 hours."
Patrick Lyden, MD, from the University of California, San Diego, and an NINDS trial investigator, wrote the editorial that accompanied the publication of the trial results in the New England Journal of Medicine. During the discussion, he said he had had more time perhaps than some others to reflect on what the importance of this trial might be. Although there are some issues that Dr. Hacke and others have pointed out, Dr. Lyden acknowledged, "I think it's very important that we not spend time on minor issues and think about the bigger picture. There should be no more doubt in anyone's mind that intravenous thrombolytic therapy is an effective treatment.
"It's time to stop taking patients to places where either there's reluctance or lack of skill or lack of capacity to give the therapy," he concluded, prompting another burst of applause.
Not Everyone Convinced?
Among the final questions was 1 on whether, in places where intra-arterial thrombolysis was available, Dr. Hacke would use that approach first before intravenous tPA after 3 hours. The question underlines a controversial move by some in the community to use interventional treatments preferentially for the treatment of stroke.
It's time to stop taking patients to places where either there's reluctance or lack of skill or lack of capacity to give the therapy.
Dr. Hacke is not among these. Until 3 hours after symptom onset, intravenous tPA is the approved treatment, he said. "In my opinion, there is no good reason, unless you identify a very peculiar situation in a given patient, like a basilar artery occlusion or a carotid T occlusion, to use any intra-arterial device in the presence of an established medical treatment, a medical treatment that yields recanalization rates on the order of 40% to 50% and that has controlled outcome data that are far better than the outcome data that come from uncontrolled, and let me frankly say, lousy case series," he replied bluntly.
That will also be true soon out to 4.5 hours, he added. If the patient is not responding and it becomes clear that there is a tight stenosis of the middle cerebral artery, for example, then an individual decision can be made to use additional rescue therapies, he said.
"But I strongly disagree with any notion that there should be a priority for intra-arterial therapy," Dr. Hacke said. He called on the interventional community to undertake clinical trials to prove the efficacy of these therapies. "And I say that as someone who started with interventional therapies while those colleagues were still in school."
At the end of the session, the moderators called for a show of hands on who, given the ECASS 3 data, would treat a patient showing up at 4 hours after symptom onset with thrombolytic therapy. Dr. Davis called the result a "sizable majority," in favor of treatment, but still, it did not include everyone.
"Can we see who would not?" Dr. Hacke quipped. "So we know where not to go."
N Engl J Med. 2008;359:1317-1329 Abstract, 1393-1395. Abstract
6th World Stroke Congress, Vienna, Austria: Abstract OR06-05. Presented September 25, 2008.
BREATH TEST AND H. PYLORI INFECTION
Breath Test More Accurate Than Serology in Diagnosing H. Pylori Infection
Sept 25 - The results of a study conducted in two peptic ulcer populations and in healthy controls suggest that the carbon-14-urea breath test (C14-UBT) is more accurate than serology in diagnosing Helicobacter pylori infection.
With sensitivity values of up to 98%, serology assays are, however, very good at ruling out infection. The relatively low accuracy is the result of low specificity, according to the report in the August 28th issue of the World Journal of Gastroenterology.
The study, conducted by Dr. Rolv-Ole Lindsetmo, from University Hospital of North Norway in Tromso, and colleagues, involved 83 vagotomized patients, 73 medically treated ulcer patients, and 88 controls who were evaluated with C14-UBT and serology assays.
Based on histologic and bacterial growth findings obtained with gastroscopic biopsy, H. pylori infection was detected in 70% of controls, 75% of medically treated patients, and in 79% of vagotomized patients, the report indicates.
The sensitivity of C14-UBT ranged from 92% to 96% and the specificity ranged from 80% to 90%. With serology, sensitivity ranged from 83% to 98%, while the specificity fell between 32% and 71%.
The level of H. pylori IgG antibodies only weakly correlated with the degree of inflammation and active ulceration, the investigators note.
"Uncritical use of H. pylori serology," the authors conclude, "will represent a considerable overestimation of H. pylori prevalence in the population tested. H. pylori serology is, on the other hand, very reliable to exclude H. pylori infection and thereby useful in screening purposes."
World J Gastroenterol 2008;14:5039-5045.
Sept 25 - The results of a study conducted in two peptic ulcer populations and in healthy controls suggest that the carbon-14-urea breath test (C14-UBT) is more accurate than serology in diagnosing Helicobacter pylori infection.
With sensitivity values of up to 98%, serology assays are, however, very good at ruling out infection. The relatively low accuracy is the result of low specificity, according to the report in the August 28th issue of the World Journal of Gastroenterology.
The study, conducted by Dr. Rolv-Ole Lindsetmo, from University Hospital of North Norway in Tromso, and colleagues, involved 83 vagotomized patients, 73 medically treated ulcer patients, and 88 controls who were evaluated with C14-UBT and serology assays.
Based on histologic and bacterial growth findings obtained with gastroscopic biopsy, H. pylori infection was detected in 70% of controls, 75% of medically treated patients, and in 79% of vagotomized patients, the report indicates.
The sensitivity of C14-UBT ranged from 92% to 96% and the specificity ranged from 80% to 90%. With serology, sensitivity ranged from 83% to 98%, while the specificity fell between 32% and 71%.
The level of H. pylori IgG antibodies only weakly correlated with the degree of inflammation and active ulceration, the investigators note.
"Uncritical use of H. pylori serology," the authors conclude, "will represent a considerable overestimation of H. pylori prevalence in the population tested. H. pylori serology is, on the other hand, very reliable to exclude H. pylori infection and thereby useful in screening purposes."
World J Gastroenterol 2008;14:5039-5045.
COMPLEX REGIMEN FOR PANCREATIC CANCER
Sept 25 - An adjuvant interferon-based chemoradiation regimen followed by gemcitabine may improve survival of patients after resected pancreatic adenocarcinoma, according to a report in the August issue of the Annals of Surgery.
Adjuvant therapy has previously been associated with improved survival over that with resection alone in these patients, the authors explain, although toxicities were significant in a large percentage of the patients.
Dr. David C. Linehan from Barnes-Jewish Hospital/Washington University Medical Center in St. Louis, Missouri, and colleagues evaluated the 2-year survival in patients with resected pancreatic adenocarcinoma treated with adjuvant chemoradiation using cisplatin, continuous infusion 5-fluorouracil, and interferon-alpha, followed by gemcitabine, given simultaneously with external beam irradiation.
About two-thirds of the patients experienced grade 3 or 4 treatment-related toxicities, the authors report, although no patients developed febrile neutropenia or sepsis while neutropenic.
All patients required some dose reduction or delay in the course of adjuvant therapy, and 16 patients (30%) were unable to complete the regimen (7 for early progression of disease, 7 for toxicity, and 2 for consent withdrawal mainly for toxicity reasons).
Median overall survival was 25 months, the investigators say, and overall survival was 75% at 1 year, 56% at 2 years, and 41% at 3 years.
"The 3-year overall survival rate in this study compares favorably to that reported in the treatment arms of other phase 3 trials," the authors write.
"Our trial provides additional evidence to support the impression that an interferon-based regimen provides improvement in 2-year survival rates for patients with pancreatic adenocarcinoma," the investigators conclude. "Toxicity remains a major concern with this treatment regimen."
"Despite the toxicities observed, the potential benefits of this treatment need to be taken in the context of these results, especially given the lethal nature of the disease," they add. "The regimen, while toxic, is manageable, and efforts to modify the regimen to reduce toxicity while maintaining or improving efficacy are warranted."
Ann Surg 2008;248:145-151
Adjuvant therapy has previously been associated with improved survival over that with resection alone in these patients, the authors explain, although toxicities were significant in a large percentage of the patients.
Dr. David C. Linehan from Barnes-Jewish Hospital/Washington University Medical Center in St. Louis, Missouri, and colleagues evaluated the 2-year survival in patients with resected pancreatic adenocarcinoma treated with adjuvant chemoradiation using cisplatin, continuous infusion 5-fluorouracil, and interferon-alpha, followed by gemcitabine, given simultaneously with external beam irradiation.
About two-thirds of the patients experienced grade 3 or 4 treatment-related toxicities, the authors report, although no patients developed febrile neutropenia or sepsis while neutropenic.
All patients required some dose reduction or delay in the course of adjuvant therapy, and 16 patients (30%) were unable to complete the regimen (7 for early progression of disease, 7 for toxicity, and 2 for consent withdrawal mainly for toxicity reasons).
Median overall survival was 25 months, the investigators say, and overall survival was 75% at 1 year, 56% at 2 years, and 41% at 3 years.
"The 3-year overall survival rate in this study compares favorably to that reported in the treatment arms of other phase 3 trials," the authors write.
"Our trial provides additional evidence to support the impression that an interferon-based regimen provides improvement in 2-year survival rates for patients with pancreatic adenocarcinoma," the investigators conclude. "Toxicity remains a major concern with this treatment regimen."
"Despite the toxicities observed, the potential benefits of this treatment need to be taken in the context of these results, especially given the lethal nature of the disease," they add. "The regimen, while toxic, is manageable, and efforts to modify the regimen to reduce toxicity while maintaining or improving efficacy are warranted."
Ann Surg 2008;248:145-151
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