CARBOPLATIN MONOCHEMOTHERAPY IN ELDERLY PATIENTS WITH NONOPERABLE TRANSITIONAL-CELL CARCINOMA OF THE BLADDER - A 2-STAGE, PHASE-II STUDY

Elderly patients with nonoperable transitional cell carcinoma of the b ladder need a rather active, but less toxic treatment than full-dose p olychemotherapy. This study was designed to determine whether the cisp latin-analogue carboplatin (which is less nephrotoxic and less neuroto xic than the parent compound) has sufficient activity against T-2-T-4 neoplasms (both nonmetastatic and metastatic) to warrant further devel opment in phase III trials. Carboplatin dose was adjusted according to creatinine clearance, with a maximum dose of 300 mg/m(2). The patient selection for this screening for activity was adjusted by the use of the 'optimal' two-stage design. Seventeen patients were enrolled, with a median age of 78 years (range: 70-85), a median performance status of 80% (range: 70-90%); 13 patients were lymph node-negative(10 T-2, 2 T-3, 1 T-4) and 4 had locoregional or distant node metastases. Nine p atients had a complete response (3 in the first, 9-patient, stage, and 6 in the second, 8-patient, stage), demonstrating that carboplatin ha d sufficient activity (at the 'desirable' target level of 35%); almost all responses were observed in T-2 patients. Six patients had stable disease, and 2 had disease progression during treatment. The toxicity was acceptable, with only 41% of patients having grade II-III hematolo gic toxicity. More than 30% of patients were estimated to be free from progressive disease (54% alive) at 24 months. In our opinion carbopla tin is suitable to be tested - in a phase III testing versus full-dose radiation therapy - as adjuvant after initial transurethral resection of the prostate in elderly patients with T-2 transitional cell carcin oma of the bladder considered radically nonoperable for medical proble ms.