title: Paclitaxel plus carboplatin in advanced carcinoma of the urothelium: an active and tolerable outpatient regimen.
abstract: OBJECTIVE
  To determine the toxicity and efficacy of an outpatient regimen of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium.
  
  
  METHODS
  Patients received paclitaxel 150 to 225 mg/m2 over 3 hours followed by carboplatin (targeted area under the concentration-time curve [AUC], 6 mg/mL x min) every 3 weeks. During phase I accrual, 16 patients were treated; 17 additional patients were enrolled at the phase II dose. The median age was 70 years (range, 47 to 82). The median serum creatinine concentration was 1.1 mg/dL (range, 0.7 to 2.7) and the median estimated creatinine clearance was 52 mL/min (range, 24 to 110).
  
  
  RESULTS
  During phase I accrual, the maximum-tolerated dose (MTD) of the regimen was not defined. Phase II accrual occurred at the paclitaxel 225 mg/m2 dose level. A total of 156 cycles were administered. The median number of cycles received was five (range, one to eight). Sensorimotor neuropathy was the principal nonhematologic toxicity. Significant granulocytopenia was common, but significant thrombocytopenia was not. Objective responses were demonstrated at all dose levels. At the phase II dose (paclitaxel 225 mg/m2 followed by carboplatin at AUC 6 mg/mL x min), the objective response rate was 50% (95% confidence interval [CI], 28% to 72%).
  
  
  CONCLUSIONS
  Paclitaxel plus carboplatin is an active and tolerable outpatient treatment for patients with advanced carcinoma of the urothelium. The ability to administer this combination over multiple cycles even to patients with advanced age and abnormal renal function makes it well suited for this patient population. Confirmatory trials of this regimen are ongoing.
authors.affiliation: University of Pennsylvania Cancer Center/Penn Cancer Clinical Trials Group, Philadelphia 19104, USA. djv@mail.med.upenn.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Vaughn
authors.forename: S B
authors.initials: SB
authors.lastname: Malkowicz
authors.forename: B
authors.initials: B
authors.lastname: Zoltick
authors.forename: R
authors.initials: R
authors.lastname: Mick
authors.forename: P
authors.initials: P
authors.lastname: Ramchandani
authors.forename: C
authors.initials: C
authors.lastname: Holroyde
authors.forename: B
authors.initials: B
authors.lastname: Armstead
authors.forename: K
authors.initials: K
authors.lastname: Fox
authors.forename: A
authors.initials: A
authors.lastname: Wein
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D014571:Urologic Neoplasms / Q000188:drug therapy*
chemical_list: D016190:Carboplatin; D017239:Paclitaxel