title: Phase II study of capecitabine and oxaliplatin in first- and second-line treatment of advanced or metastatic colorectal cancer.
abstract: OBJECTIVE
  To determine the efficacy and tolerability of combining oxaliplatin with capecitabine in the treatment of advanced nonpretreated and pretreated colorectal cancer.
  
  
  METHODS
  Forty-three nonpretreated patients and 26 patients who had experienced one fluoropyrimidine-containing regimen for advanced colorectal cancer were treated with oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,250 mg/m(2) bid on days 1 to 14 every 3 weeks. Patients with good performance status (World Health Organization grade 0 to 1) were accrued onto two nonrandomized parallel arms of a phase II study.
  
  
  RESULTS
  The objective response rate was 49% (95% confidence interval [CI], 33% to 65%) for nonpretreated and 15% (95% CI, 4% to 35%) for pretreated patients. The main toxicity of this combination was diarrhea, which occurred at grade 3 or 4 in 35% of the nonpretreated and 50% of the pretreated patients. Grade 3 or 4 sensory neuropathy, including laryngopharyngeal dysesthesia, occurred in 16% of patients on both cohorts. Capecitabine dose reductions were necessary in 26% of the nonpretreated and 45% of the pretreated patients in the second treatment cycle. The median overall survival was 17.1 months and 11.5 months, respectively.
  
  
  CONCLUSIONS
  Combining capecitabine and oxaliplatin yields promising activity in advanced colorectal cancer. The main toxicity is diarrhea, which is manageable with appropriate dose reductions. On the basis of our toxicity experience, we recommend use of capecitabine in combination with oxaliplatin 130 mg/m(2) at an initial dose of 1,250 mg/m(2) bid in nonpretreated patients and at a dose of 1,000 mg/m(2) bid in pretreated patients.
authors.affiliation: Institute of Medical Oncology, Inselspital, Switzerland. markus.borner@insel.ch
authors.forename: Markus M
authors.initials: MM
authors.lastname: Borner
authors.forename: Daniel
authors.initials: D
authors.lastname: Dietrich
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Rudolf
authors.initials: R
authors.lastname: Morant
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Honegger
authors.forename: Martin
authors.initials: M
authors.lastname: Wernli
authors.forename: Richard
authors.initials: R
authors.lastname: Herrmann
authors.forename: Bernhard C
authors.initials: BC
authors.lastname: Pestalozzi
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Saletti
authors.forename: Silvia
authors.initials: S
authors.lastname: Hanselmann
authors.forename: Samuel
authors.initials: S
authors.lastname: Müller
authors.forename: Peter
authors.initials: P
authors.lastname: Brauchli
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Arnaud D
authors.initials: AD
authors.lastname: Roth
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil