title: Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma.
abstract: BACKGROUND
  Patients with urothelial carcinoma are not always amenable to cisplatin-based chemotherapy. The authors previously reported that they achieved a 60% response rate in patients who failed on cisplatin-based combination chemotherapy (methotrexate, vinblastine, doxorubicin, and cisplatin) by using a convenient outpatient regimen of gemcitabine (G) and paclitaxel (P) every 2 weeks. A multicenter trial was initiated in 5 Italian centers to evaluate this regimen as first-line chemotherapy.
  
  
  METHODS
  From January 2003 to April 2005, 54 patients who had histologically proven, measurable disease (according to Response Evaluation Criteria in Solid Tumors) with a World Health Organization (WHO) performance status (PS) from 0 to 2, metastatic or inoperable urothelial carcinoma, no prior systemic cytotoxic or biologic treatment, a creatinine clearance >or=40 mL per minute, and bilirubin <20 micromol/L received G at a dose of 2500 mg/m(2) in 30 minutes and P at a dose of 150 mg/m(2) in 3 hours every 2 weeks. Granulocyte-colony-stimulating factor (G-CSF) was given for 5 to 7 days for neutropenia toxicity of grade >or=3 (grading determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 guidelines). From 6 to 12 courses were planned. All patients received at least 1 cycle of therapy and were included in all analyses.
  
  
  RESULTS
  The median patient age was 67 years (range 34-78 years), and the median WHO PS was 1 (range, 0-2). Metastases occurred in the lung in 17 patients (31%), in lymph nodes in 26 patients (54%), in the bladder in 20 patients (37%), in bone in 8 patients (15%), and in the liver in 8 patients (15%). Fifty-nine percent of patients had >1 site of disease, and 13% of patients had >or=3 sites of disease. In total, 343 cycles were administered. Five patients achieved a complete response, and 15 patients achieved a partial response; thus, the overall response rate was 37% in an intent-to-treat analysis. Hematologic toxicity was predominant but manageable. G-CSF was used in only 6% of cycles. The median survival was 13.2 months, and the median time to disease progression was 5.8 months.
  
  
  CONCLUSIONS
  In a multicenter study, G and P was found to be a well-tolerated outpatient regimen. This regimen demonstrated promise and may be considered in patients who are unable to receive cisplatin.
authors.affiliation: Department of Medical Oncology, San Camillo Forlanini Hospitals, Circonvallazione Gianicolense 87, Rome 00152 Italy. fabiocalabro1@alice.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Calabrò
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Gerardo
authors.initials: G
authors.lastname: Rosati
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzione
authors.forename: Luca
authors.initials: L
authors.lastname: Frassineti
authors.forename: Teodoro
authors.initials: T
authors.lastname: Sava
authors.forename: Eugenio Donato
authors.initials: ED
authors.lastname: Di Paula
authors.forename: Silvia
authors.initials: S
authors.lastname: Alonso
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine