Effect of relative cumulative dose-intensity on survival of patients with urothelial cancer treated with M-VAC.

PURPOSE To evaluate the received dose-intensity in a mature data set of patients with advanced urothelial cancer who received at least one cycle of the methotrexate (M), vinblastine (V), Adriamycin ([A], doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (C) regimen (M-VAC). PATIENTS AND METHODS Received dose-intensity was evaluated over time by summing doses over cycles for each patient, cumulating treatment times, and assuming four cycles of chemotherapy were planned. Relative cumulative dose-intensity was then calculated for individual patients at the end of each cycle. To assess a relationship with survival, relative cumulative dose-intensity was then used as a time-dependent covariate in Cox regression. RESULTS The median follow-up was 6 years and median survival 13.3 months, with 20 patients alive at the time of analysis. Out of a maximum of 1.0, the median relative dose-intensity for the M-VAC combination decreased from .69 to .59 from cycle 1 to cycle 4. Similarly, a decrease from .68 to .62 and from .80 to .72 was observed for A and C, respectively. The median received dose-intensity for A was 6.0 mg/m2/wk, and for C 14 mg/m2/wk. Neither the four-cycle relative cumulative dose-intensity for the M-VAC combination, nor the relative cumulative dose-intensities for A or C were found to be significant prognostic factors. CONCLUSION The absence of an effect for received dose-intensity on survival may reflect the low dose-intensities of the components of the regimen actually delivered in this study. The results question whether the individual agents can be escalated sufficiently, with growth factor support, to improve significantly complete response proportions, a prerequisite for increasing the proportion of long-term survivors.