ORLANDO, Fla.—Neoadjuvant chemotherapy with methotrexate(Drug information on methotrexate), doxorubicin(Drug information on doxorubicin), vinblastine(Drug information on vinblastine), and cisplatin(Drug information on cisplatin) (MVAC) had promising results in the treatment of muscle-invasive bladder cancer, among the 64 patients enrolled on the Japan Clinical Oncology Group Study 0209 who were treated with the combination. Unfortunately, the trend toward improved overall survival seen in the study was not statistically significant due to underpowering of the study.
Patients assigned to MVAC did have improved progression-free survival compared with patients who underwent radical cystectomy with no prior chemotherapy. The median 5-year progression-free survival of patients assigned neoadjuvant chemotherapy was 69.1% compared with 56.4% in patients undergoing radical cystectomy alone (HR = 0.61; P = .04).
“Although neoadjuvant chemotherapy with cisplatin/gemcitabine is widely used for muscle-invasive bladder cancer, neoadjuvant chemotherapy with MVAC can still be considered promising,” said study presenter Hiroshi Kitamura, MD, PhD, of the department of urology, Sapporo Medical University, Sapporo, Japan.
Abstract discussant, Dean F. Bajorin, MD, of Memorial Sloan-Kettering Cancer Center, agreed.
“In my opinion, [this study] does confirm MVAC as a standard of care,” Bajorin said. “It was only two cycles rather than three, and it was underpowered in regard to the study, but there was a survival difference relative to the number of patients on the trial.”
Kitamura explained to attendees that the trial was closed early due to slow accrual. The study design anticipated a sample size of 180 patients in each arm to detect a difference in 5-year overall survival between the arms. In the six years of open enrollment, Kitamura and colleagues at 28 institutions in Japan randomly assigned 64 patients to two cycles of neoadjuvant chemotherapy with MVAC followed by radical cystectomy and 66 patients to the surgery alone.
A Data Safety Monitoring Committee recommended publication of the results at the second planned interim analysis done in September 2012.
“This was because neoadjuvant chemotherapy with gemcitabine(Drug information on gemcitabine) and cisplatin is widely used in clinical practice,” Kitamura said. “The committee judged that it would be difficult to present a confirmatory conclusion at the final analysis of whether or not the neoadjuvant chemotherapy was superior to the radical cystectomy arm in terms of survival because of insufficient sample size.”
The 5-year overall survival of patients who received neoadjuvant chemotherapy was 72.3% compared with 62.4% for patients undergoing surgery alone (HR = 0.65; P = .07).
When the researchers looked at pathological outcomes, they found that the proportion of pT0 in the neoadjuvant arm was 37.3% compared with 9.4% in surgery alone (P < .01). More than one-third of patients in the surgery alone arm had pathological lymph node metastasis compared with 13.6% of patients in the neoadjuvant arm.
No differences in perioperative complications were noted between the two groups except for an increase in lymph leakage in the radical cystectomy arm (12.3% vs 1.7%).