title: Gemcitabine and ifosfamide as a second-line treatment for cisplatin-refractory metastatic urothelial carcinoma: a phase II study.
abstract: Few treatment options are available for cisplatin-refractory urothelial carcinoma. We evaluated the efficacy and safety of a new regimen composed of gemcitabine and ifosfamide as a second-line salvage chemotherapy for the disease. The gemcitabine and ifosfamide regimen consists of gemcitabine 800 mg/m/day intravenously for 30 min on days 1, 8, and 15; ifosfamide 1500 mg/m/day intravenously for 24 h on days 8-10; and mesna 800 mg intravenously bolus before ifosfamide and 1500 mg/m/day intravenously for 24 h on days 8-11. Cycles are repeated every 28 days. Between 1998 and 2005, 23 patients (median age 66) unresponsive to cisplatin-based chemotherapy (n=10) or who had tumor progression within 6 months of a previous response to cisplatin-based therapy (n=13) were enrolled. The median interval between the two chemotherapy regimens was 1.8 months (range 0.9-5.6). In total, 82 treatment cycles (median 3, range 1-8) were given. The overall response rate was 22% (95% confidence interval 5-39) with one complete response and four partial responses. Twenty-one patients succumbed to the disease. The median progression-free survival and overall survival were 3.5 and 4.8 months, respectively. Grade 3 or 4 leukopenia and thrombocytopenia occurred in 10 and eight patients, respectively. One, two and two patients complicated with grade 3 vomiting, diarrhea and stomatitis were present, respectively. No grade 3 or 4 neurotoxicity or nephrotoxicity was seen in these patients. The gemcitabine and ifosfamide regimen has an acceptable toxicity profile, but shows insufficient clinical activity in patients with cisplatin-refractory urothelial carcinoma to warrant further testing.
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lin
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Hsu
authors.forename: Chao-Yuan
authors.initials: CY
authors.lastname: Huang
authors.forename: Hsiao-Yi
authors.initials: HY
authors.lastname: Keng
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Tsai
authors.forename: Kuo-How
authors.initials: KH
authors.lastname: Huang
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Yeong-Shiau
authors.initials: YS
authors.lastname: Pu
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003841:Deoxycytidine; D002945:Cisplatin; D007069:Ifosfamide; D000093542:Gemcitabine