COMBINATION CHEMOTHERAPY FOR METASTATIC OR LOCALLY ADVANCED GENITOURINARY SQUAMOUS-CELL CARCINOMA - A PHASE-II STUDY OF METHOTREXATE, CISPLATIN AND BLEOMYCIN

Purpose: The prognosis of patients with advanced squamous cell carcino ma of genitourinary origin is poor. While single agent chemotherapy re sults mainly in partial responses of short duration, data on the effic acy of combination chemotherapy are extremely limited. We determined t he response rate and toxicity of a combination of 3 of the most active agents, methotrexate, cisplatin and bleomycin, in patients with advan ced genitourinary squamous cell carcinoma. Materials and Methods: Pati ents with metastatic or locally advanced genitourinary squamous cell c arcinoma were eligible for study. Treatment consisted of 200 mg./m.(2) methotrexate on days 1, 15 and 22, and 20 mg./m.(2) cisplatin and 10 mg./m.(2) bleomycin on days 2 through 6 during a 28-day cycle. Results : Of the 30 patients who enrolled in the trial 29 were evaluable for r esponse. Objective response was achieved in 16 patients (55%, 95% conf idence interval 36 to 72), 4 of whom achieved a complete response (14% ). Median objective response duration was 4.7 months (range 1.9 to 39. 5). Median survival of the entire group was 11.5 months (range 1.5 to 87.0). Of the patients 9 achieved disease-free status, including 6 fol lowing consolidation surgery or radiation therapy. Median survival of these 9 patients (34.4 months, range 9.6 to 87.0) was significantly gr eater (p = 0.0003) than that of patients who did not become disease-fr ee (7.0 months, range 1.5 to 38.6). Grade III or IV hematological toxi city in 116 courses included neutropenia (13%) and thrombocytopenia (6 %). Among 30 patients evaluable for toxicity serious nonhematological toxic effects included stomatitis (3%) and renal toxicity (7%). There was 1 death from neutropenic sepsis. Conclusions: Methotrexate, cispla tin and bleomycin combination chemotherapy for genitourinary squamous cell carcinoma results in a high but short lived overall response rate , and a low complete response rate with manageable toxicity. A multidi sciplinary approach to achieve disease-free status may provide the bes t opportunity to effect survival and should be the focus of future tri als.