A phase II study of gemcitabine and irinotecan in patients with locally advanced or metastatic bladder cancer.

Background: The objectives of the current study were to evaluate the safety and efficacy of gemcitabine and irinotecan (Irinogem) in patients with metastatic bladder cancer. Irinotecan and gemcitabine are newer-generation chemotherapeutic agents with different mechanisms of action, nonoverlapping toxicity profiles, and synergistic activity in vitro.

Methods: Sixteen patients have been enrolled, of which 13 are evaluable for response. The median age is 68.5 years (range, 52 to 82 y). According to the Bajorin prognostic model for metastatic bladder cancer, 8 patients were classified as "low risk" and 8 as "intermediate risk." Gemcitabine 1000 mg/m and irinotecan 100 mg/m were administered on days 1 and 8 of each 3-week cycle. All patients had histologically proven transitional cell cancer of the bladder with bidimensionally measurable disease. All but 2 patients were chemotherapy naive at enrollment.

Results: The median number of cycles administered was 4. Among the 13 patients evaluable for efficacy, objective radiographic response was documented in 8 patients (2 complete and 6 partial responses), 4 had stable disease, and 1 progressed on therapy. Median progression-free survival was 8.78 months (95% confidence interval, 5.98-15.38) and median overall survival was 13.51 months (95% confidence interval, 8.02-21.93). Toxicity evaluated in all 16 patients was modest: 2 episodes of febrile neutropenia, grades 3 to 4 neutropenia in 4 patients, grades 3 to 4 diarrhea in 2 patients, grades 3 to 4 fatigue in 1 patient, grades 3 to 4 nausea/vomiting in 2 patients, grades 3 to 4 neurological toxicity in 1 patient, and no grades 3 to 4 thrombocytopenia. No toxic deaths were noted. One patient discontinued therapy due to grade 4 fatigue, 1 due to stroke, 1 due to grade 4 colitis, 1 due to progressive disease, and 1 declined to participate in the trial after receiving the first cycle of therapy.

Conclusions: The results of the current study suggested that the combination of Irinogem was an effective treatment for patients with metastatic bladder cancer, with manageable toxicities. The study was closed early due to delays in accrual and loss of funding. Hence, the study lacks adequate power to make definite conclusions. Further studies in multi-institutional setting in patients with normal and compromised renal function are warranted.