title: 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.
authors.affiliation: Department of Cancer Medicine, Peter MacCallum Cancer Institute, Melbourne, Australia.
authors.forename: B L
authors.initials: BL
authors.lastname: Hillcoat
authors.forename: D
authors.initials: D
authors.lastname: Raghavan
authors.forename: J
authors.initials: J
authors.lastname: Matthews
authors.forename: R
authors.initials: R
authors.lastname: Kefford
authors.forename: K
authors.initials: K
authors.lastname: Yuen
authors.forename: R
authors.initials: R
authors.lastname: Woods
authors.forename: I
authors.initials: I
authors.lastname: Olver
authors.forename: J
authors.initials: J
authors.lastname: Bishop
authors.forename: B
authors.initials: B
authors.lastname: Pearson
authors.forename: G
authors.initials: G
authors.lastname: Coorey
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D011897:Random Allocation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014571:Urologic Neoplasms / Q000188:drug therapy*
chemical_list: D002945:Cisplatin; D008727:Methotrexate