- Ann Oncol. 2009 Jun 23. [Epub ahead of print]
Multicenter phase II study of gemcitabine and oxaliplatin in advanced nasopharyngeal carcinoma--correlation with excision repair cross-complementing-1 polymorphisms.
Ma BB, Hui EP, Wong SC, Tung SY, Yuen KK, King A, Chan SL, Leung SF, Kam MK, Yu BK, Zee B, Chan AT.
Department of Clinical Oncology at the Sir Y K Pao Center for Cancer, Hong Kong Cancer Institute and Li Ka Shing Institute for Health Science, State Key Laboratory in Oncology in South China, Chinese University of Hong Kong, Hong Kong SAR.
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a platinum-sensitive cancer and excision repair cross-complementing group 1 (ERCC1) polymorphisms have been shown to predict survival in several cancers following platinum therapy. PATIENTS AND METHODS: This multicenter study evaluated the activity of oxaliplatin and prolonged infusion of gemcitabine ('GEMOX' regimen) in recurrent NPC. Baseline blood samples were genotyped for the presence of ERCC1-118 gene polymorphisms. Results: Forty-two patients were recruited, of whom most (61%) had metastatic disease. Of the 40 patients evaluated for response, the respective overall response and disease control rates were 56.1% and 90.2%. At a median follow-up of 14.8 months, the respective median overall survival and time to progression were 19.6 months [95% confidence interval (CI) = 12.8-22 months] and 9 months (95% CI = 7.3-10 months). Grade 3-4 toxic effects were uncommon. The distribution of ERCC1-118 genotypes from 29 patients was C/C (n = 17, 40.5%), C/T (n = 10, 23.8%) and T/T (n = 2, 4.8%). No differences in survival or response rates were found between genotypes. CONCLUSIONS: GEMOX is active in the treatment of recurrent NPC. Detection of single-nucleotide gene polymorphisms from genomic DNA in peripheral blood is feasible in NPC and further studies are warranted.
Δευτέρα 29 Ιουνίου 2009
SECOND LINE CHEMOTHERAPY WITH GEMOX FOR NASOPHARYNGEAL CARCINOMA
CETUXIMAB AND KRAS MUTATIONS FOR SQUAMOUS ESOPHAGEAL CANCER
- Ann Oncol. 2009 Jun 23. [Epub ahead of print]
Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie.
Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F.
Third Department of Internal Medicine (Hematology/Medical Oncology).
BACKGROUND: This study assessed the activity of the mAb cetuximab in combination with cisplatin and 5-fluorouracil (5-FU) in advanced esophageal squamous cell carcinoma. PATIENTS AND METHODS: For a maximum of six 29-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2), days 1-5 (CF), either alone or in combination with cetuximab (CET-CF; 400 mg/m(2) initial dose followed by 250 mg/m(2) weekly thereafter). The primary end point was tumor response. Tumor material was obtained for analysis of KRAS mutation status. RESULTS: Sixty-two eligible patients were included, 32 receiving CET-CF and 30 CF. Cetuximab did not exacerbate grade 3/4 toxicity, except for rash (6% versus 0%) and diarrhea (16% versus 0%). The overall response rate according to RECIST criteria was 19% and 13% and the disease control rate 75% and 57% for the CET-CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in 37 evaluated samples. CONCLUSION: Cetuximab can be safely combined with CF chemotherapy and may increase the efficacy of standard CF chemotherapy.
Κυριακή 28 Ιουνίου 2009
TRASTUZUMAB USE HAS THE SAME EFFECT FOR ICH2+FISH+ PATIENTS
Disease-Free Survival According to Degree of HER2 Amplification for Patients Treated With Adjuvant Chemotherapy With or Without 1 Year of Trastuzumab: The HERA Trial
Purpose To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) –positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy.
Patients and Methods IHC and/or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry. FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival (DFS) after a median 2 years of follow-up.
Results Central FISH results were available for 2,071 (61%) of the 3,401 patients randomized to the 2 arms. Among patients with FISH-positive disease, (1) the hazard ratios for trastuzumab versus no trastuzumab were 0.56 (95% CI, 0.32 to 0.99) for locally IHC2+ cases (n = 340) and 0.80 (95% CI, 0.40 to 1.61) for centrally IHC2+ cases (n = 299). There was no significant prognostic relationship between (2a) HER2 FISH ratio, (2b) HER2 copy number, or (3) polysomy and DFS in the control arm or predictive relationship defining differential benefit from trastuzumab.
Conclusion There was no evidence for reduced benefit of trastuzumab in HER2 IHC2+FISH+ cases. The degree of HER2 amplification does not influence prognosis or benefit from adjuvant trastuzumab in patients treated with prior adjuvant chemotherapy.A STUDY WITH CONTRADICTORY RESULTS WITH A SIMILAR STUDY PRESENTED AT ASCO
Comparison of Sentinel Lymph Node Biopsy Alone and Completion Axillary Lymph Node Dissection for Node-Positive Breast Cancer
Purpose For women with breast cancer, the role of completion axillary lymph node dissection (ALND) after identification of nodal metastases by sentinel lymph node biopsy (SLNB) has been questioned. Our objectives were to assess national nodal evaluation practice patterns and to examine differences in recurrence and survival for SLNB alone versus SLNB with completion ALND.
Patients and Methods From the National Cancer Data Base (1998 to 2005), women with clinically node-negative breast cancer who underwent SLNB and who had nodal metastases were identified. Practice patterns and outcomes were examined for patients who underwent SLNB alone versus SLNB with completion ALND (median follow-up, 63 months).
Results Of 97,314 patients, 20.8% underwent SLNB alone, and 79.2% underwent SLNB with completion ALND. In 2004 to 2005, patients were significantly more likely to undergo SLNB alone if they were older, had smaller tumors, or were treated at non–National Cancer Institute–designated cancer centers. In patients with macroscopic nodal metastases (n = 20,075 during 1998 to 2000), there was a nonsignificant trend toward better outcomes for completion ALND (v SLNB alone) after analysis was adjusted for differences between the two groups: axillary recurrence (hazard ratio [HR], 0.58; 95% CI, 0.32 to 1.06) and overall survival (HR, 0.89; 95% CI, 0.76 to 1.04). In patients with microscopic nodal metastases (n = 2,203 during 1998 to 2000), there were no significant differences in axillary recurrence or survival for patients who underwent SLNB alone versus completion ALND.
Conclusion Compared with SLNB alone, completion ALND does not appear to improve outcomes for breast cancer patients with microscopic nodal metastases; however, there was a nonsignificant trend toward better outcomes with completion ALND for those with macroscopic disease.BREAST CANCER LYMPH NODE METASTASIS AND AGE
Relationship Between Age and Axillary Lymph Node Involvement in Women With Breast Cancer
Purpose To study the relation between the presence of axillary lymph node (LN) involvement and age in breast cancer.
Patients and Methods The breast cancer database of the University Hospitals Leuven contains complete data on 2,227 patients with early breast cancer consecutively treated between 2000 and 2005. A multivariate piecewise logistic regression model was used to analyze LN involvement in relation to age at diagnosis. A similar analysis was then performed on a large, independent, population-based database from the Eindhoven Cancer Registry to investigate whether the effects of the Leuven model could be replicated.
Results We observed a piecewise effect of age. That is, women up to 70 years of age were less likely to have positive LNs with increasing age (odds ratio per 10-year increase, 0.87). In contrast, older women were more likely to have positive LNs with increasing age. However, for older women, the effect of age interacted with tumor size (P = .0044), suggesting that increasing age is associated with increased risk of LN involvement, mainly in small tumors. These findings were replicated in the Eindhoven Cancer Registry database.
Conclusion Axillary LN involvement varies with age at diagnosis; its probability decreases with increasing age up to the age of approximately 70 years, but increases again thereafter. However, this increase is mainly seen in smaller tumors and suggests a different behavior of small breast cancers in older adult patients. We hypothesize that decreased immune defense mechanisms, related with aging, may play a role in earlier invasion into LNsADJUVANT RADIOTHERAPY FOR pT3 PROSTATE CANCER
Phase III Postoperative Adjuvant Radiotherapy After Radical Prostatectomy Compared With Radical Prostatectomy Alone in pT3 Prostate Cancer With Postoperative Undetectable Prostate-Specific Antigen: ARO 96-02/AUO AP 09/95
From the Department of Radiation Oncology, University Hospital Ulm, Ulm; Departments of Urology and Radiation Oncology, Charité Universitätsmedizin, Campus Benjamin-Franklin, Berlin; Department of Pathology, Helios-Clinic Wuppertal, Wuppertal; Departments of Radiation Oncology and Urology, University Hospital Münster, Münster; Department of Radiation Oncology, General Hospital Hagen, Hagen; Departments of Urology and Radiation Oncology, University Hospital Homburg/Saar, Homburg/Saar; Department of Urology, Euro-Med-Clinic Fürth, Fürth; Department of Urology, General Hospital Berlin-Herzberge, Berlin-Herzberge; Department of Urology, Diakonissinnen-Krankenhaus Dessau, Dessau; Departments of Urology and Radiation Oncology, General Hospital Fulda, Fulda; Department of Urology, University Hospital Dresden, Dresden; and WiSP GmbH, Langenfeld, Germany.
Corresponding author: Thomas Wiegel, MD, Department of Radio Oncology, University Hospital Ulm, Albert-Einstein-Allee 23, D-89081 Ulm, Germany; e-mail: thomas.wiegel@uniklinik-ulm.de.
Purpose Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP.
Methods After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival.
Results Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%.
Conclusion Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.PEGINTRON FOR ADJUVANT MELANOMA
Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma: A Phase III Randomized Controlled Trial of Health-Related Quality of Life and Symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group
Purpose Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL effects of adjuvant pegylated IFN-
Methods A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation (n = 629) or PEG-IFN-
Results At 3.8 years of median follow-up, for the primary end point, recurrence-free survival (RFS), risk was reduced by 18% (hazard rate = 0.82; P = .01) in the PEG-IFN-
Conclusion PEG-IFN-
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