title: A phase II study of gemcitabine and capecitabine in metastatic renal cancer: a report of Cancer and Leukemia Group B protocol 90008.
abstract: BACKGROUND
  The objective of this study was to verify previous reports of activity with gemcitabine plus a fluoropyrimidine in patients with metastatic renal cell cancer in a multiinstitutional setting.
  
  
  METHODS
  Eligibility included a Zubrod performance status from 0 to 2, no prior gemcitabine or fluoropyrimidine therapy, and normal organ function. Patients received gemcitabine at a dose of 1000 mg/m2 on Days 1, 8, and 15 and capecitabine at a dose of 830 mg/m2 twice daily on Days 1 through 21 on a 28-day cycle with specified dose reductions for baseline renal insufficiency. The primary endpoint was the response rate, which was assessed every 8 weeks. The statistical plan tested the hypothesis that the response rate was 5% versus an alternative of 15%.
  
  
  RESULTS
  Sixty patients were enrolled, and 4 of those patients never started treatment. Of the 56 evaluable patients, 79% of patients underwent prior nephrectomy, 75% of patients received prior systemic therapy, and 75% of patients had clear cell histology. Risk stratification revealed that 34%, 43%, and 16% of patients were in Risk Groups 1, 2, and 3, respectively. Toxicity (graded according to the National Cancer Institute's Common Toxicity Criteria [version 2.0]) included Grade 3 or 4 neutropenia in 45% of patients, Grade 2 or greater fatigue in 32% of patients, Grade 2 or greater nausea in 29% of patients, Grade 2 or greater hand-foot reaction in 39% of patients, and Grade 2 or greater diarrhea in 22% of patients. Six patients responded (11%; 95% confidence interval, 4-22%), and the overall median survival was 14.5 months.
  
  
  CONCLUSIONS
  Gemcitabine plus capecitabine had modest activity in patients with metastatic renal cancer, although the degree of activity and its associated toxicity would not support further evaluation in a Phase III trial of unselected patients. More focused investigations to identify patients most likely to benefit or to enhance activity with additional agents would be reasonable.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois 60637, USA. wstadler@medicine.bsd.uchicago.edu
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Brian
authors.initials: B
authors.lastname: Rini
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: Enrique
authors.initials: E
authors.lastname: Davila
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Robert
authors.initials: R
authors.lastname: Barrier
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine