Neoadjuvant Chemotherapy with CMV Improves Outcome for Invasive Bladder Cancer

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Long-term results from a phase III trial show that neoadjuvant chemotherapy with CMV (cisplatin, methotrexate, and vinblastine) improves the outcome for patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy.

“Three cycles of CMV before cystectomy or radiotherapy results in a 16% reduction in the risk of death, corresponding to an increase in 3-year survival from 50% to 56%, 10-year survival from 30% to 36%, and median survival time of 7 months (from 37 to 44 months),” the investigators reported in the Journal of Clinical Oncology. The median follow-up was 8.0 years. Based on these results and two other large randomized trials that confirmed a “statistically significant and clinically relevant survival benefit,” the authors concluded, “neoadjuvant chemotherapy followed by definitive local therapy should be viewed as state of the art, as compared with cystectomy or radiotherapy alone, for deeply invasive bladder cancer.”

The international multicenter trial randomly assigned 976 patients with histologically proven muscle-invasive urothelial cell carcinoma of the bladder (T2 grade 3, T3, or T4a and N0/X, M0) to three cycles of CMV (n = 491) or no chemotherapy (n = 485). “The choice of definitive treatment used in this trial was based on patient or physician choice and was not randomly assigned, and the trial was designed explicitly not to compare various definitive local treatments,” the investigators reported. “Thus, no conclusions should be drawn from the data presented concerning the relative merit of cystectomy compared with radiotherapy.”

The authors noted, “more than 70% of participating clinicians were of the opinion that an improvement in survival of 10% would be needed to justify the use of neoadjuvant CMV in routine practice. This magnitude of benefit has not been achieved with this trial, which shows, along with the meta-analysis published in 2005 by the Advanced Bladder Cancer Collaboration, a clear benefit in overall survival of only 5% to 6% at 3 years.”

The increase in survival that was seen “will need to be balanced against the toxicity and other disadvantages of chemotherapy (eg, the cost to the patient in terms of treatment time and impact on quality of life),” the authors stated. Five patients assigned to CMV died from toxic effects during treatment in the study, a morality rate of 1%, and 26% experienced impaired renal function requiring dose decreases or delay. Grade 3 or 4 toxic effects included leukopenia in 16% of patients, neutropenic fever in 10%, and thrombocytopenia in 6.5%.

International Collaboration of Trialists: J Clin Oncol 29:2171-2177, 2011.




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