TY - JOUR
T1 - A phase II study of gemcitabine and capecitabine in patients with advanced renal cell cancer
T2 - Southwest oncology group study S0312
AU - Van Veldhuizen, Peter J.
AU - Hussey, Michael
AU - Lara, Primo N
AU - Mack, Philip
AU - Gandour-Edwards, Regina F
AU - Clark, Joseph I.
AU - Lange, Marianne K.
AU - Crawford, David E.
PY - 2009/10
Y1 - 2009/10
N2 - 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/m on days 1, 8, and 15 and with capecitabine at 625 mg/m 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.
AB - 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/m on days 1, 8, and 15 and with capecitabine at 625 mg/m 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.
KW - Chemotherapy
KW - Gemcitabine
KW - MTOR
KW - PTEN
KW - Renal cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=70350640904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70350640904&partnerID=8YFLogxK
U2 - 10.1097/COC.0b013e3181925176
DO - 10.1097/COC.0b013e3181925176
M3 - Article
C2 - 19487915
AN - SCOPUS:70350640904
VL - 32
SP - 453
EP - 459
JO - American Journal of Clinical Oncology
JF - American Journal of Clinical Oncology
SN - 0277-3732
IS - 5
ER -