ORLANDO – Cisplatin-based neoadjuvant chemotherapy plus cystectomy improved the overall survival of patients with muscle-invasive bladder cancer beyond that achieved with cystectomy alone; however, the results did not reach statistical significance in the Japan Clinical Oncology Group Study, JCOG0209.
In a randomized trial of 130 patients accrued over a 6-year period, overall survival at 5 years was 72.3% for patients who had two cycles of chemotherapy followed by radical cystectomy and 62.4% for patients who had radical cystectomy alone. The overall survival results were not significant because of insufficient sample size, according to Dr. Hiroshi Kitamura of Sapporo (Japan) Medical University.
Median progression-free survival time, however, was significantly longer at 99 months in the group who received neoadjuvant chemotherapy plus cystectomy compared with 78 months in those who had radical cystectomy alone (HR = 0.61, P = .04). Progression-free survival at 5 years was 69.1% and 56.4%, respectively.
The Japan Clinical Oncology Group Study, JCOG0209, examined the MVAC regimen of methotrexate, vinblastine, doxorubicin (Adriamycin), and cisplatin followed by radical cystectomy. MVAC comprised methotrexate (30 mg/m2) on days 1, 15, and 22; vinblastine (3 mg/m2) on days 2, 15, and 22; Adriamycin (30 mg/m2) on day 2; and cisplatin (70 mg/m2) on day 2.
Because neoadjuvant therapy with gemcitabine and cisplatin is now widely used to treat invasive bladder cancer, and considered to provide a 5%-8% overall survival advantage, the Data and Safety Monitoring Committee recommended early publication of the results, Dr. Kitamura said at the annual Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology. The findings indicate that the MVAC regimen can still be considered promising.
"Although (the chemotherapy regimen) was two cycles, and the study was underpowered," chemotherapy plus radical cystectomy were confirmed as the standard of care for muscle-invasive bladder cancer, commented Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, New York, who was not involved in the study. "I do not think we need to include nontreatment arms in these trials anymore."
Between March 2003 and March 2009, researchers randomized 130 patients to receive two cycles of MVAC neoadjuvant chemotherapy followed by radical cystectomy (64 patients) or to radical cystectomy alone (66 patients). Patient registration was terminated early because of slow accrual.
The primary endpoint was overall survival. Secondary endpoints were progression-free survival, surgery-related complication rate, adverse events during neoadjuvant chemotherapy, the rate of no residual tumor in radical cystectomy specimens (pT0), and quality of life.
Results at the second interim analysis showed that overall survival was better with MVAC plus surgery (median, 102 months) than with radical cystectomy alone (median, 81 months), but the difference did not achieve statistical significance because the sample size was small (HR = 0.65, P = .07).
At the time of radical cystectomy, clinical stage was pT0 in 37% of the MVAC arm and 9% in the radical cystectomy arm (P less than .01).
Dr. Kitamura said he had no relationships to disclose. Dr. Bajorin disclosed that he has been a consultant or adviser for Bristol-Myers Squibb, Dendreon, Lilly, and Novartis. He has received honoraria from Lilly, and research funding from Amgen, Dendreon, Genentech, Genta, GlaxoSmithKline, and Novartis.
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