title: Phase II trial of capecitabine and rHu-interferon-alpha-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity.
abstract: BACKGROUND
  Capecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-alpha (IFNalpha), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNalpha-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted.
  
  
  METHODS
  Eligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m(2) twice daily on days 1-14 and 22-36, combined with IFNalpha-2a 3.0 MU/m(2) subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m(2) twice daily on days 1-14 and 22-36 in the subsequent 18 patients.
  
  
  RESULTS
  Responses were seen in 4 of 32 patients (12%) (95% confidence interval 4% to 29%), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6-15.0). There were 12 patients (38%) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63%. Toxicity was moderate to severe and required dose reductions in 88% of patients. There were 23 patients who had grade > or =3 toxicity.
  
  
  CONCLUSIONS
  The combination of capecitabine and IFNalpha-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.
authors.affiliation: Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH 41950, USA.
authors.forename: Ena
authors.initials: E
authors.lastname: Segota
authors.forename: Tarek
authors.initials: T
authors.lastname: Mekhail
authors.forename: Thomas
authors.initials: T
authors.lastname: Olencki
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Brenda
authors.initials: B
authors.lastname: Wacker
authors.forename: Bruno
authors.initials: B
authors.lastname: Osterwalder
authors.forename: Paul
authors.initials: P
authors.lastname: Elson
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil