title: Front-line Treatment with Gemcitabine, Paclitaxel, and Doxorubicin for Patients With Unresectable or Metastatic Urothelial Cancer and Poor Renal Function: Final Results from a Phase II Study.
abstract: OBJECTIVE
  To estimate the response rate of gemcitabine, paclitaxel, and doxorubicin in patients with advanced urothelial carcinoma, we conducted a phase II clinical trial. Patients with renal insufficiency cannot receive standard cisplatin-based chemotherapy for urothelial carcinoma, and carboplatin-based regimens have proved unsatisfactory. Secondary end points for this study included overall survival, safety of the regimen, and safety of same-day pegfilgrastim dosing.
  
  
  METHODS
  A two-stage design was chosen with target response rate of 40%. Key inclusion criteria were metastatic or unresectable urothelial carcinoma, no prior chemotherapy, glomerular filtration rate <60 mL/min, and no dialysis. Gemcitabine (900 mg/m(2)), paclitaxel (135 mg/m(2)), and doxorubicin (40 mg/m(2)) were administered on day 1 of each 14-day cycle. Pegfilgrastim was given with every cycle on either day 1 or optionally day 2.
  
  
  RESULTS
  Forty patients were enrolled and 39 were treated. Median age was 72 years (range 51-89). There were 7 complete and 15 partial responses, for a response rate of 56.4% (95% confidence interval, 39.6-72.2). Most cycles (82.8%) were given with same-day pegfilgrastim. Notable grade 3 and 4 nonhematologic toxicities were fatigue and mucositis (10.3% each). There were 4 episodes of neutropenic fever (4 of 198 cycles [2%]; 4 of 39 patients [10.3%]) and no treatment-related deaths. Median overall survival was 14.4 months.
  
  
  CONCLUSIONS
  The combination of gemcitabine, paclitaxel, and doxorubicin is effective first-line chemotherapy for patients with advanced urothelial carcinoma and renal insufficiency. Neutropenic prophylaxis was acceptable whether pegfilgrastim was given immediately or 24 hours after chemotherapy.
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Arlene O
authors.initials: AO
authors.lastname: Siefker-Radtke
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Campbell
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Munsell
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Harris
authors.affiliation: Cancer Research for the Ozarks, Springfield, MO.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Carolla
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: Pagliaro.Lance@mayo.edu.
authors.forename: Lance C
authors.initials: LC
authors.lastname: Pagliaro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000556:secondary; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000209:etiology; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D017239:Paclitaxel; D000069585:Filgrastim; D000093542:Gemcitabine