262 Background: We had previously reported the phase I/II study of a combination regimen of gemcitabine, etoposide, and cisplatin (GEP) in second-line treatment for patients with advanced UC. This study sought to examine the combination chemotherapy of GEP as first-line treatment for advanced urothelial carcinoma (UC) to assess efficacy, feasibility, prognostic factors, and the impact of postchemotherapy surgery on outcomes. Methods: Forty-two patients were treated with GEP as first-line treatment for metastatic or unresectable locally advanced UC. GEP was recycled every 4 weeks. Etoposide and cisplatin were given on days 1 through 3 at doses of 60 mg/m2 and 20 mg/m2, respectively, and gemcitabine was given on days 1, 8, and 15 at a dose of 800 mg/m2. Results: The median patient age was 64 years. Twenty-three male patients and 19 female patients were included. The primary cancer site is urinary bladder in 21 patients, and upper urinary tract in 21 patients. Nineteen had visceral/bone metastases, 16 had disease restricted to lymph nodes, and the remaining 7 had unresectable disease at primary site. The median number of GEP courses was 4. Thirty of 42 assessable patients (71.4%) demonstrated objective responses. At a median follow-up of 14.6 months, the median overall survival time (OS) was 16.2 months. Twenty-four of 30 responders underwent postchemotherapy surgeries. Median OS in the patients with postchemotherapy surgery was 25.4 months. In the multivariable analysis, anemia and visceral/bone metastasis were significant pretreatment prognostic factors for OS. In addition, being male and anemic were independent poor prognostic factors in patients with postchemotherapy surgery. Grade 3-4 neutropenia, anemia and thrombocytopenia occurred in 84%, 73% and 57%. There were no treatment-related deaths. Conclusions: GEP as first-line chemotherapy in combined-multimodality treatment is active and moderately tolerable for advanced UC. Postchemotherapy surgery may yield favorable outcomes in patients who achieved objective responses. Anemia and visceral/bone metastasis were independent pretreatment predictors for OS.
Clinical evidence for the first-line treatment of advanced urothelial carcinoma: Current paradigms and emerging treatment options
