title: Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium.
  
  
  METHODS
  Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles.
  
  
  RESULTS
  Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up.
  
  
  CONCLUSIONS
  This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.
authors.affiliation: Hospital General Universitari Vall d'Hebron, Bacelona, Spain. bellmunt@hg.vhebron.ed
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.forename: V
authors.initials: V
authors.lastname: Guillem
authors.forename: L
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: J L
authors.initials: JL
authors.lastname: González-Larriba
authors.forename: J
authors.initials: J
authors.lastname: Carles
authors.forename: E
authors.initials: E
authors.lastname: Batiste-Alentorn
authors.forename: A
authors.initials: A
authors.lastname: Sáenz
authors.forename: M
authors.initials: M
authors.lastname: López-Brea
authors.forename: A
authors.initials: A
authors.lastname: Font
authors.forename: M
authors.initials: M
authors.lastname: Nogué
authors.forename: R
authors.initials: R
authors.lastname: Bastús
authors.forename: M A
authors.initials: MA
authors.lastname: Climent
authors.forename: J J
authors.initials: JJ
authors.lastname: de la Cruz
authors.forename: J
authors.initials: J
authors.lastname: Albanell
authors.forename: J M
authors.initials: JM
authors.lastname: Banús
authors.forename: E
authors.initials: E
authors.lastname: Gallardo
authors.forename: E
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: H
authors.initials: H
authors.lastname: Cortés-Funes
authors.forename: J
authors.initials: J
authors.lastname: Baselga
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine