title: Biweekly paclitaxel and gemcitabine for patients with advanced urothelial cancer ineligible for cisplatin-based regimen.
abstract: BACKGROUND
  To avoid cisplatin-related gastrointestinal, renal and other toxicity while maintaining efficacy in the palliative setting or second line chemotherapeutic regimen for cisplatin-resistant urothelial cancer, chemotherapeutic regimens have been investigated that do not include cisplatin. The current study was designed to evaluate efficacy, clinical feasibility and safety of gemcitabine and paclitaxel (GP) regimen in patients with metastatic urothelial cancer who were ineligible for standard cisplatin-based combination chemotherapy.
  
  
  METHODS
  Gemcitabine 2500 mg/m(2) and paclitaxel 150 mg/m(2) were administered intravenously every 2 weeks for 23 patients (17 males and 6 females) with advanced urothelial cancer who were ineligible for cisplatin-based chemotherapy; metastatic disease being resistant to cisplatin-based chemotherapy regimen in 14, heavy toxicity in prior cisplatin-based chemotherapy in three, poor ECOG performance in two and impaired renal function in four. Average age was 67 (53-77). Performance status was 0 in 18 patients, 1 in three patients and 2 in two patients.
  
  
  RESULTS
  The overall response rate was 30% (95% CI 15.6-50.8%). Of the 23 patients, no patient attained CR and 7 patients had PR. In the cisplatin-resistant group, the response rate was 14.2% (2/14; 95% CI 4.0-39.9%). In the remaining patients ineligible for cisplatin, the response rate was 55.5% (5/9; 95% CI 26.6-81.1%). The median duration of response was 4 months (range 3-8). The median duration of survival for all patients was 12.1 months (95% CI 8.6-15.5). Myelosuppression, predominantly neutropenia, was the most common serious toxicity and toxicity of Grade 3 or greater was observed in six patients (26%). Among non-hematological toxicity, neuralgia was the most commonly observed and occurred in nine patients (39%) although no patient had toxicity of Grade 3 or greater. Three patients had interstitial pneumonitis possibly attributed to gemcitabine. One patient developed severe bilateral disease after two cycles of the regimen, which was partially resolved with corticosteroid therapy.
  
  
  CONCLUSIONS
  GP regimen is effective in some patients with cisplatin-resistant urothelial cancer and promising as second line chemotherapy. GP regimen is more effective and well tolerated as first line chemotherapy in patients ineligible for cisplatin-based chemotherapy. Toxicity is generally mild but care must be taken for patients with risk of interstitial pneumonitis. A further larger scale study is required to confirm the efficacy of the GP regimen.
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shin
authors.initials: S
authors.lastname: Higashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Takeshiko
authors.initials: T
authors.lastname: Segawa
authors.forename: Eijiro
authors.initials: E
authors.lastname: Nakamura
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Itoh
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kamoto
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D014571:Urologic Neoplasms / Q000188:drug therapy*; D019459:Urothelium / Q000473:pathology*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine