Neoadjuvant Treatment of Stages T2 to T4 Bladder Cancer with Cis-Platinum, Cyclophosphamide and Doxorubicin

Abstract

In an ongoing phase II study 17 patients with potentially operable transitional cell carcinoma of the bladder (stages T2 to T4, Nx, Mo) have been treated with intravenous cis-platinum (50 mg.per m.2), cyclophosphamide (400 mg.per m.2) and doxorubicin (40 mg.per m.2). They were to receive 3 treatments at 3-week intervals before cystectomy and 2 treatments at 3-week intervals commencing 5 weeks after cystectomy. Of 17 patients 14 (82 per cent) completed all 3 preoperative treatments but only 7 (41 per cent) continued on to complete the entire 5 treatments. In most cases incomplete therapy was due to patient refusal. Toxicity was low as measured by World Health Organization standards. Of the 17 patients 9 (53 per cent) exhibited objective tumor response (pathological downstaging or greater than 50 per cent reduction of tumor volume determined by either computerized tomography scan and/or endoscopic examination. When the determination was made by endoscopy the changes were dramatic and not borderline.) No patient demonstrated a pathological complete response. All 9 of the responders (100 per cent) remain clinically free of disease at a median follow-up of 19 months (range 4 to 30 months). The 8 nonresponders have done poorly with 5 dead of disease, 1 alive with pelvic recurrence and 2 free of disease at 4 and 12 months. These tumor response rates compare favorably with other cis-platinum-based combination regimens. The response to the chemotherapy appears to be an important prognostic indicator. Phase III trials must be conducted to determine whether this neoadjuvant chemotherapy regimen has a significant effect on long-term patient survival.

Neo‐adjuvant (Pre‐emptive) Cisplatin Therapy in Invasive Transitional Cell Carcinoma of the Bladder

“…Cisplatin was well tolerated and did not present problems with administration in the context of a large multicentre trial; 12% did not receive a second course of cisplatin, which is comparable to the 13% who did not receive preliminary chemotherapy in the study reported by Shearer et al (1988) and18% reported by McCullough et al (1989); 85% of the West Midlands patients received a third course with 10% having a reduced dose. Neither study attempted any maintenance chemotherapy, which was attempted by both Shearer et al (1988) andMcCullough et al (1989), with only 59 and 41% receiving their maintenance chemotherapy. Long courses of adjuvant chemotherapy cannot be given to h e majority of patients with invasive bladder cancer.…”

Intra-arterial Chemotherapy and Concurrent Radiotherapy for Invasive Bladder Cancer

“…In recently reported neoadjuvant chemotherapy for patients with advanced bladder Cancer, regimens using M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin), CISCA (cyclophosphamide, doxorubicin and cisplatin) or CMV (cisplatin, methotrexate and vinblastine) are widely used. The respective response rates are summarized as follows: M-VAC induced 24 % cCR and 27 % cPR by TUR in 50 patients with T 2 _ 4 N 0 M 0 tumors(Scher et al, 1988); CISCA 0% pCR and 53 % pathological down-staging or greater than 50% reduction of tumor volume in 17 patients with T2-4N x Mo tumors(McCullough et al, 1989); CMV 10% pCR, 49% pathological downstaging and 41 % no change in 44 patients with T3-4N0/ N( + )Mo tumors (Mafezzini et al, 1991).…”