title: Accelerated chemotherapy in the treatment of urothelial cancer.
abstract: To evaluate an alternative treatment for advanced or metastatic urothelial cancers, a dose-intensive combination chemotherapy regimen using carboplatin, methotrexate, vincristine and cisplatin was given to 60 patients over a 3-year period (1990 to 1993). There were 26 patients with locally advanced disease and 34 with metastatic disease; 49 patients were evaluable for response. A complete response was noted in four patients (8%) and a partial response in 15 (31%), for an overall response rate of 39%. The median survival was 12 months. Two- and 5-year survival rates were 25.5% (95% confidence interval CI) 15.2-37.0) and 7.3% (95% CI 2.2-16.4) respectively. Failure-free survival was 15.3% (95% CI 7.5-25.6) at 2 years and 5.9% (95% CI 1.6-14.4) at 5 years, with a median of 8 months. For the responders, the median duration of response was 14 months, with a range of 2-59+ months. Toxicity included myelosuppression (28% grade 4/5 neutropenia, 19% grade 4 thrombocytopenia), peripheral neuropathy (54% grade 1 and 23% grade 2/3) and ototoxicity (21% grade 1, 19% grade 2). This schedule of dose-intensified platinum-based chemotherapy for bladder cancer resulted in significant neurotoxicity without evidence of enhanced response rates or survival. Regimens such as methotrexate, vinblastine, doxorubicin and cisplatin should remain standard. Accelerated regimens may be useful in situations were it is necessary to administer chemotherapy over a short time (e.g. as part of combined modality treatment).
authors.affiliation: Academic Unit of Radiotherapy and Oncology, Royal Marsden Hospital, NHS Trust, Sutton, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Huddart
authors.forename: F N
authors.initials: FN
authors.lastname: Lau
authors.forename: T
authors.initials: T
authors.lastname: Guerrero-Urbano
authors.forename: G
authors.initials: G
authors.lastname: Jay
authors.forename: A
authors.initials: A
authors.lastname: Norman
authors.forename: A
authors.initials: A
authors.lastname: Horwich
authors.forename: D P
authors.initials: DP
authors.lastname: Dearnaley
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology