OBJECTIVES: Gemcitabine plus capecitabine has moderate efficacy in patients with advanced renal cell cancer (RCC) but has considerable toxicity. We evaluated the efficacy and toxicity of a modified dose-schedule of this doublet in patients with metastatic RCC. METHODS: Chemotherapy-naive patients were treated with gemcitabine at 900 mg/m2 on days 1, 8, and 15 and with capecitabine at 625 mg/m2 twice daily on days 1 through 21, and every 28 days thereafter. The primary end point was response rate (RR). No further evaluation of this regimen would be pursued if the RR was ≤ 5%. In an exploratory analysis, we also evaluated potential markers of prognosis and treatment response, including thymidylate synthase, PTEN, pAKT, pmTOR, XRCC1, and ERCC1. RESULTS: Of 43 patients, 1 was ineligible and 2 were not analyzable. There was 1 complete response and 3 partial responses, for an overall RR of 10% (95% CI = 3, 24). Nineteen patients (48%) had stable disease. The 6-month freedom-from-treatment-failure and overall survival rates were 20% (95% CI = 8, 32) and 75% (95% CI = 62, 88), respectively. Median survival time was 23 months (95% CI = 10, 37). One patient each experienced grade 4 neutropenia, fatigue, thrombocytopenia, and hemolysis with renal failure. The most common grade 3 toxicities were neutropenia (12 patients), fatigue (5), and leucopenia (4). Patients with a best response of stable disease or better were more likely to have decreased expression of PTEN and increased expression of pmTOR. CONCLUSIONS: Gemcitabine plus capecitabine at this reduced dose-schedule benefits a small percentage of patients with RCC with an acceptable toxicity profile.
OBJECTIVES:Gemcitabine plus capecitabine has moderate efficacy in patients with advanced renal cell cancer (RCC) but has considerable toxicity. We evaluated the efficacy and toxicity of a modified dose-schedule of this doublet in patients with metastatic RCC. METHODS: Chemotherapy-naive patients were treated with gemcitabine at 900 mg/m2 on days 1, 8, and 15 and with capecitabine at 625 mg/m2 twice daily on days 1 through 21, and every 28 days thereafter. The primary end point was response rate (RR). No further evaluation of this regimen would be pursued if the RR was ≤ 5%. In an exploratory analysis, we also evaluated potential markers of prognosis and treatment response, including thymidylate synthase, PTEN, pAKT, pmTOR, XRCC1, and ERCC1. RESULTS: Of 43 patients, 1 was ineligible and 2 were not analyzable. There was 1 complete response and 3 partial responses, for an overall RR of 10% (95% CI = 3, 24). Nineteen patients (48%) had stable disease. The 6-month freedom-from-treatment-failure and overall survival rates were 20% (95% CI = 8, 32) and 75% (95% CI = 62, 88), respectively. Median survival time was 23 months (95% CI = 10, 37). One patient each experienced grade 4 neutropenia, fatigue, thrombocytopenia, and hemolysis with renal failure. The most common grade 3 toxicities were neutropenia (12 patients), fatigue (5), and leucopenia (4). Patients with a best response of stable disease or better were more likely to have decreased expression of PTEN and increased expression of pmTOR. CONCLUSIONS:Gemcitabine plus capecitabine at this reduced dose-schedule benefits a small percentage of patients with RCC with an acceptable toxicity profile.
Authors: Mark J Ratain; Tim Eisen; Walter M Stadler; Keith T Flaherty; Stan B Kaye; Gary L Rosner; Martin Gore; Apurva A Desai; Amita Patnaik; Henry Q Xiong; Eric Rowinsky; James L Abbruzzese; Chenghua Xia; Ronit Simantov; Brian Schwartz; Peter J O'Dwyer Journal: J Clin Oncol Date: 2006-04-24 Impact factor: 44.544
Authors: Robert J Motzer; Brian I Rini; Ronald M Bukowski; Brendan D Curti; Daniel J George; Gary R Hudes; Bruce G Redman; Kim A Margolin; Jaime R Merchan; George Wilding; Michelle S Ginsberg; Jennifer Bacik; Sindy T Kim; Charles M Baum; M Dror Michaelson Journal: JAMA Date: 2006-06-07 Impact factor: 56.272
Authors: S Negrier; B Escudier; C Lasset; J Y Douillard; J Savary; C Chevreau; A Ravaud; A Mercatello; J Peny; M Mousseau; T Philip; T Tursz Journal: N Engl J Med Date: 1998-04-30 Impact factor: 91.245
Authors: Walter M Stadler; Susan Halabi; Brian Rini; Marc S Ernstoff; Enrique Davila; Joel Picus; Robert Barrier; Eric J Small Journal: Cancer Date: 2006-09-15 Impact factor: 6.860
Authors: Stephen L Richey; Pheroze Tamboli; Chaan S Ng; E Lin; Zita D Lim; John C Araujo; Eric Jonasch; Padmanee Sharma; Lance C Pagliaro; Nizar M Tannir Journal: Am J Clin Oncol Date: 2013-10 Impact factor: 2.339