Gemcitabine and ifosfamide (GI) as a second-line systemic chemotherapy for cisplatin-failed advanced urothelial carcinoma (UC)

Abstract

4739 Background: Cisplatin-based combination chemotherapy is the mainstay treatment for advanced UC. There is no standard salvage regimen for patients who fail cisplatin-based chemotherapy. We evaluated the efficacy and safety of the combination of gemcitabine and ifosfamide as a second-line treatment for advanced UC. Methods: Between Dec. 1998 and Dec. 2003, 15 patients (M:F = 12:3) with a median age 66 (48 - 76) were enrolled. All did not respond to cisplatin-based chemotherapy or progressed from previously cisplatin-sensitive status in less than 6 months (4 with CMV, 5 with P-HDFL [Proc ASCO 2001 abstr 3128], 6 with TP-HDFL [Proc ASCO 2003 abstr 1637]). GI consisted of gemcitabine 800 mg/m2/d IV 30 min on D 1, 8 & 15; ifosfamide 1500 mg/m2/d IV 24 hr on D 8–10; and mesna 800 mg IV bolus before ifosfamide & 1500 mg/m2/d IV 24 hr on D 8 - 11, repeated every 28 days. Results: A total of 48 courses had been given, with an average of 3.4 courses per patient (range: 1–6). Among 14 patients eligible for response evaluation, there were 1 complete response, 4 partial responses, 4 stable diseases and 2 progressive diseases. One patient is still under the protocol treatment now. The overall response rate was 36% (95% C.I. 10–62%) with 7% complete response. The median survival was 6 months (range: 1 to 26+). Fourteen patients were eligible for analysis of toxicity. Grade III/IV leukopenia, anemia, and thrombocytopenia were noted in 6 (14 cycles), 3 (5 cycles), and 6 (11 cycles) patients, respectively. Grade III/IV nausea, vomiting, mucositis, and diarrhea were noted in 0, 1, 3, and 0 patient, respectively. Conclusions: GI is active against cisplatin-failed advanced UC with an acceptable toxicity profile. No significant financial relationships to disclose.