title: Platinum-free combination chemotherapy in patients with advanced or metastatic transitional cell carcinoma.
abstract: BACKGROUND
  Platinum-based regimens have improved response rates and survival in patients with advanced transitional cell carcinoma (TCC) of the urothelial tract. However, the toxicities of platinum-based chemotherapy are considerable. Regimens with reduced toxicity that are applicable to a broader group of TCC patients without sacrificing activity therefore are of interest.
  
  
  METHODS
  Because gemcitabine, paclitaxel, and methotrexate have each been reported to possess single-agent activity in this disease, the authors evaluated the tolerability and efficacy of fixed doses of paclitaxel (100 mg/m(2) over 3 hours) and methotrexate (30 mg/m(2)) with escalating doses of gemcitabine (800-1000 mg/m(2)), all given on Days 1 and 8 every 21 days, in patients with previously untreated unresectable or metastatic TCC.
  
  
  RESULTS
  Twenty-five patients were enrolled. Two patients were ineligible and were excluded from analysis. Because no dose-limiting toxicity occurred in the first 4 patients who were given gemcitabine at a dose of 800 mg/m(2), the gemcitabine dose was escalated to 1000 mg/m(2) in the next 21 patients. Of the 21 patients assessable for response, 6 had achieved a complete response (CR) and 6 had achieved a partial response, for an overall response rate of 57%. An additional patient was converted to a CR surgically. The median overall and progression-free survival times were 18 months and 9.2 months, respectively. Toxicity was predominantly neutropenia: Grade 3 in 9 patients (39%) and Grade 4 in 4 patients (17%) (according to the Southwest Oncology Group Toxicity Criteria, version 12/1994). One patient died of septic shock associated with febrile neutropenia after three cycles.
  
  
  CONCLUSIONS
  The regimen of gemcitabine, paclitaxel, and methotrexate at this dose and schedule was found to possess activity in patients with locally advanced or metastatic TCC. Further studies of this regimen are warranted.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis Cancer Center, Sacramento, California 95817, USA. primo.lara@ucdmc.ucdavis.edu
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Meyers
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Law
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Dawson
authors.forename: Joan
authors.initials: J
authors.lastname: Houston
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lauder
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D008727:Methotrexate; D000093542:Gemcitabine