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

To estimate the response rate to 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.

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.

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% CI, 39. 6-72. 2). Most (82. 8%) cycles were given with same-day pegfilgrastim. Notable grade 3 and 4 non-hematologic toxicities were fatigue and mucositis (10. 3% each). There were 4 episodes of neutropenic fever (4/198 cycles [2%]; 4/39 patients [10. 3%]) and no treatment related deaths. Median overall survival was 14. 4 months.

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.

Urology. 2015 Dec 23 [Epub ahead of print]

Arlene O Siefker-Radtke, Matthew T Campbell, Mark F Munsell, Deborah R Harris, Robert L Carolla, Lance C Pagliaro

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. , Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. , Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, and. , Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. , Cancer Research for the Ozarks, Springfield, MO. , Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Current affiliation: Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN.  

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