Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: A Southwest Oncology Group study

Purpose: Patients with locally advanced bladder cancer or who are not medic ally fit for surgery are a therapeutic dilemma. Radiotherapy with or withou t single agent cisplatin has been the major therapeutic modality. A phase I I Southwest Oncology Group trial investigated the efficacy and feasibility of 5-fluorouracil, cisplatin and radiation in this patient subset. Materials and Methods: Eligible patients had muscle invasive bladder cancer (clinical stages T2-T4) with nodal involvement at or below the level of bi furcation of the iliac vessels, were medically or surgically inoperable, or refused cystectomy. Patients underwent pretreatment cystoscopy and detaile d tumor mapping, and were treated with 75 mg./m.(2) cisplatin on day 1 and 1 gm./m.(2) daily, 5-fluorouracil on days 1 to 4 and definitive radiotherap y. Chemotherapy was repeated every 28 days, twice during and twice after ra diation. Results: From October 1993 to April 1998, 60 patients were enrolled in stud y. Of the 56 eligible patients 34% had unresectable tumors, 21% were not me dically fit for surgery and 45% refused cystectomy. Overall, 68% of the pat ients had clinical T3 tumors or greater and 22% had nodal metastasis. Treat ment was completed as planned in 32 of 56 (57%) patients. The most frequent grade 3 or 4 toxicities were neutropenia, stomatitis or mucositis, diarrhe a, neuropathy and nausea. There were 53 patients who were evaluable for res ponse, although response was not determined for 18. The overall response ra te was 51% (95% confidence interval [CI] 37 to 65) based on intent to treat with a complete response rate of 49% (95% CI 35 to 63). Estimated median s urvival of the 56 patients was 27 months (95% CI 21 to 40 months) with an o verall 5-year survival of 32%. The 5-year survival of the 25 patients who r efused surgery was 45%. Conclusions: Concurrent 5-fluorouracil, cisplatin and radiation therapy is feasible. Despite a promising complete response rate, the overall 5-year su rvival suggests the need for more effective systemic therapy. The 5-year su rvival of patients who refused cystectomy suggests that this combined modal ity may provide another alternative to cystectomy for these patients.