title: A phase ii study of gemcitabine and capecitabine in patients with advanced renal cell cancer: Southwest Oncology Group Study S0312.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Kansas Medical Center, Kansas City, KS 66160, USA. pvanveldhuizen@kumc.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Van Veldhuizen
authors.forename: Michael
authors.initials: M
authors.lastname: Hussey
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Regina
authors.initials: R
authors.lastname: Gandour-Edwards
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Lange
authors.forename: David E
authors.initials: DE
authors.lastname: Crawford
mesh_terms: 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
chemical_list: 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