Twenty patients with locally advanced and/or metastatic transitional cell cancer of the urinary tract were treated with cyclophosphamide 500 mg/m2, Adriamycin (doxorubicin) 40 mg/m2 and cis-platinum (CDDP) 40 mg/m2 given every three weeks for 2 cycles, alternating with methotrexate 40 mg/m2 weekly for six weeks (CAP-M). Five of thirteen (38%) evaluable patients responded, with a significant prolongation of survival. Toxicity in 18 evaluable patients was mild to moderate. Methotrexate can be combined with CAP with significant reduction in dosage of cyclophosphamide, Adriamycin and CDDP and reduced toxicity, without major loss of efficacy. The precise role of methotrexate in combination chemotherapy of bladder cancer remains to be defined.
Cancer 51:1-4, 1983.
RANSITIONAL CELL CARCINOMA of the urinary tract,
T of which cancer of the bladder is the most common, is an important disease with an annual incidence in the United States of approximately 30,000. Invasive bladder cancer cames a high mortality despite radical surgery and radiation. There is a continued interest in developing more effective cytotoxic chemotherapy. Previous studies have demonstrated activity against transitional cell carcinoma for several drugs. Reported response rates include cyclophosphamide 35%;' cis-platinum (CDDP) 35%;'.2 Adriamycin (doxorubicin) 23%;3 mitomycin-C 20%; and 5-fluorouracil (5-Fu) reported 35%, but many cases not critically e~aluated.~ Limited clinical experience, principally in the United Kingdom suggested that methotrexate might also have significant activity, with a reported 26% response rate.5,6 A recent study has confirmed a 26% response rate in 4 1 patients, with 38% of previously untreated patients re~ponding.~ In all of the above studies the majority of responses were partial responses of relatively short duration (median, approximately 4-6 months).
Combination chemotherapy has not yet demonstrated a clear advantage over single agent therapy. Sev-From the