Gemcitabine and cisplatin in locally advanced and metastatic bladder cancer; 3-or 4-week schedule?

Background. Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published. Material and methods. We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule. Results. A total of 212 patients received GC (3-week; n=151, 4-week; n=61). We found no statistical differences in overall survival between the two schedules (hazard ratio 1.15, 95% CI 0.83-1.59), p=0.40). Five-year survival rates were 14.9% and 11.8% for the 3- and 4-week schedule, respectively (p=0.94). Response rates were 59.7% and 55.6%, respectively (p=0.61). Toxicity was less pronounced in the 3-week schedule with regards to neutropenia, thrombocytopenia, and transfusion rates. Hematologic toxicity at day 15 in the 4-week schedule was common, leading to dose omissions in 47% of cycles. Dose intensity for gemcitabine was accordingly lower in the 4 week-schedule. The higher dose intensity of cisplatin in the 3-week schedule, did not lead to increased renal toxicity. In 13 patients with impaired renal function, cisplatin was split into 2 days, which was feasible and efficient. Conclusion. Efficacy parameters for the GC 3-week schedule were comparable to those for the 4-week schedule, whereas toxicity was less pronounced. The 3-week schedule may be an effective and feasible alternative GC-schedule.