title: Phase II evaluation of docetaxel-modulated capecitabine in previously treated patients with non-small cell lung cancer.
abstract: OBJECTIVE
  Based on the preclinical observation of upregulation of thymidine phosphorylase, the last enzymatic step in the conversion of capecitabine to 5-fluorouracil, by docetaxel along with good clinical tolerability of the combination of docetaxel and capecitabine using an optimized schedule in a previous phase I trial, we conducted this phase II study of this combination in patients with refractory or relapsed non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with NSCLC previously treated with at least one platinum- or paclitaxel-based regimen received docetaxel 36 mg/m(2) on days 1, 8, and 15 and capecitabine 625 mg/m(2) twice daily on days 5 to 18, every 4 weeks. The primary objective of the study was evaluation of progression-free survival (PFS) 26 weeks from initiation of treatment.
  
  
  RESULTS
  Thirty-six evaluable patients received 104 cycles of the combination. Severe toxicities were infrequent with only one patient requiring toxicity-related hospitalization. The 26-week PFS rate was 25% (95% confidence interval, 12-42) with an intent to treat median survival and 1-year survival rate of 9.1 months and 37%, respectively. Among 31 patients with measurable disease (Response Evaluation Criteria in Solid Tumors criteria), eight (26%; 95% confidence interval, 12-45) achieved partial responses.
  
  
  CONCLUSIONS
  The combination of capecitabine and weekly docetaxel is well tolerated in previously treated patients with NSCLC. The relatively high 26-week PFS and 1-year survival, as well as the high response rate observed, encourages further evaluation of this regimen in NSCLC, either in randomized trials for refractory patients or as a potential treatment option for chemotherapy naive patients.
authors.affiliation: Division of Hematology/Oncology, Arthur G. James Cancer Hospital, Ohio State University, 320 West Tenth Avenue, Columbus, OH 43210, USA.
authors.forename: Tamila
authors.initials: T
authors.lastname: Kindwall-Keller
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Otterson
authors.forename: Donn
authors.initials: D
authors.lastname: Young
authors.forename: Anterpreet
authors.initials: A
authors.lastname: Neki
authors.forename: Tamara
authors.initials: T
authors.lastname: Criswell
authors.forename: Gerard
authors.initials: G
authors.lastname: Nuovo
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
authors.forename: Robert
authors.initials: R
authors.lastname: Diasio
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D000069287:Capecitabine; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil