title: Treatment of refractory urothelial carcinoma with alternating paclitaxel, methotrexate, cisplatin (TMP) and 5-fluorouracil, alpha-interferon, cisplatin (FAP).
abstract: We assessed the activity and safety of a biochemotherapy regimen in which courses of paclitaxel, methotrexate, and cisplatin were alternated with courses of 5-fluorouracil, alpha-interferon, and cisplatin in the treatment of refractory urothelial carcinoma. Forty patients were enrolled in the study. In the phase I portion, 15 patients were treated according to an escalating dosage regimen designed to determine the maximum tolerated dose. A total of 30 patients received treatment according to the maximum tolerated dose regimen: methotrexate (30 mg/m(2)) given iv on days 1 and 22; paclitaxel (175 mg/m(2)) given iv over 3 h on day 1; cisplatin (70 and 25 mg/m(2)) administered iv on days 1 and 22, respectively; 5-fluorouracil (400 mg/m(2)) given iv by continuous infusion daily for 5 days beginning on day 22; and alpha-interferon (4 mIU/m(2)) given SC daily for 5 days simultaneously with the 5-fluorouracil infusions. The regimen was repeated at 42-day intervals. The 40 treated patients had an overall response rate of 43%, a complete response rate of 18%, and a median survival time of 44 weeks. Most of the toxic effects were hematologic: Grade 4 neutropenia occurred in 30% of patients (12 patients) and Grade 3 thrombocytopenia in 20% (8 patients). Even though this alternating biochemotherapy regimen was active for patients with refractory urothelial carcinoma, its activity was not better than that of certain single cytotoxic agents. Furthermore, the complicated dosing schedule and toxic effects of the regimen precluded its routine use in the treatment of urothelial carcinoma.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. stu@notes.mdacc.tmc.edu
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Tu
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: Danai
authors.initials: D
authors.lastname: Daliani
authors.forename: Christos N
authors.initials: CN
authors.lastname: Papandreou
authors.forename: Jeri
authors.initials: J
authors.lastname: Kim
authors.forename: Dung-Tsa
authors.initials: DT
authors.lastname: Chen
authors.forename: Dallas L
authors.initials: DL
authors.lastname: Williams
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage*; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy*
chemical_list: D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil