A phase ii study of gemcitabine and capecitabine in patients with advanced renal cell cancer: Southwest Oncology Group Study S0312.
OBJECTIVE
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.
Van Veldhuizen
Peter J
PJ
Department of Internal Medicine, Division of Hematology/Oncology, University of Kansas Medical Center, Kansas City, KS 66160, USA. pvanveldhuizen@kumc.edu
Hussey
Michael
M
Lara
Primo N
PN
Mack
Philip C
PC
Gandour-Edwards
Regina
R
Clark
Joseph I
JI
Lange
Marianne K
MK
Crawford
David E
DE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism; D016896:Treatment Outcome; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D013940:Thymidylate Synthase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C071447:ERCC1 protein, human; D004720:Endonucleases; D051059:PTEN Phosphohydrolase; C497446:VHL protein, human; D005472:Fluorouracil; D000093542:Gemcitabine