A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract.

Abstract

One hundred eight patients with recurrent or metastatic transitional cell carcinoma of the urothelial tract were randomized to receive cisplatin (C) 80 mg/m2 on day 1 every 4 weeks, or methotrexate (M) 50 mg/m2 on days 1 and 15 plus C 80 mg/m2 on day 2 every 4 weeks (C + M). Fifty-three eligible patients were randomized to C + M and 55 to C. In the C + M arm, 45% of patients responded (complete response [CR], 9%) and 31% (CR, 9%) in the C arm (P = .18). In the C arm, 20 patients failing or relapsing after C received M. Two patients responded, and four with progressive disease (PD) and one with a previous partial response (PR) showed no change. The median survival was 8.7 months (C + M arm) and 7.2 months (C arm), P = .7. Relapse-free survival was not significantly different, but C + M was associated with a significantly increased time to disease progression (median, 5.0 months, v 2.8 months for C arm). The response of untreated patients (37%) was not different from those with prior treatment (39%). On the C + M arm, 92% of patients and 96% of patients on the C arm received 85% or more of the scheduled C dose. Significantly more grade 3 or 4 hematological toxicity (27% v 2%; P = .01) and mucositis (20% v 0%; P = .0005) occurred in patients on the C + M arm. Although the initial response rates seen on the combination arm look superior, and the time to disease progression is increased, these effects have not translated into a clinically important increase in the duration of survival and were associated with increased toxicity.

CMV chemotherapy for advanced transitional cell carcinoma

“…Three early deaths were probably treatment related but no definitive proof was available. Toxic deaths have been reported in other series in approximately 2-4% of cases (Harker et al, 1985;Hillcoat et al, 1989;Logothetis et al, 1990a;Stemnberg et al, 1989;Tannock et al, 1989).…”

“…Accepting the toxicity of cisplatinbased chemotherapy becomes questionable when long-term survivors are rare. In the randomised studies above the overall response rates to cisplatin alone were only 16%, 20% and 31% respectively (Troner et al, 1987;Hillcoat et al, 1989;Soloway et al, 1983). What is beyond question is that cisplatin is the drug responsible for the most toxicity.…”

“…Similarly the Southeastern Cancer Study Group Trial (Troner et al, 1987) showed no differences between cisplatin alone and cisplatin, doxorubicin and cyclophosphamide in combination (116 patients entered). Hillcoat et al (1989) compared cisplatin alone with cisplatin plus methotrexate and reported no significant differences. The study was small (108 patients) and the potential for missing significant treatment differences was again noted (Scher, 1989).…”

Metastatic Urothelial Cancer: Evaluation of Prognostic Factors and Change in Prognosis during the Last Twenty Years

“…Several factors have been shown to influence prognosis, and the results have not been uniform [2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. This variability may be explained by the choice of factors analyzed and by selection of patients.…”

Chemotherapy for advanced bladder cancer: 'Midsummer Night's Dream' or 'Much Ado About Nothing'?

“…However, single agent chemotherapy has been compared with combination regimens in several randomised trials (Table I), most of which have failed to reveal a statistically significant or clinically relevant survival benefit from combination chemotherapy. Moreover, in these trials, combination regimens have caused significantly greater levels of toxicity (Soloway et al, 1983;Khandekar et al, 1985;Troner et al, 1987;Hillcoat et al, 1989). Despite the lack of evidence supporting the use of combination regimens, investigators have continued to develop more intricate (and toxic) regimens, predicated on the hope that high response rates would ultimately translate into improved survival.…”