title: Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil.
abstract: BACKGROUND
  Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy.
  
  
  METHODS
  A phase II study examining chronomodulated XELOX(30) (XELOX(30chron)): oxaliplatin: 130 mg/m(2) on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m(2), 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%; median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%.
  
  
  CONCLUSIONS
  XELOX(30chron) is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX(30) and XELOX(30chron) as first-line therapy in patients with mCRC.
authors.affiliation: Department of Oncology, Odense University Hospital, Denmark. camilla.qvortrup@ouh.regionsyddanmark.dk
authors.forename: C
authors.initials: C
authors.lastname: Qvortrup
authors.forename: M
authors.initials: M
authors.lastname: Yilmaz
authors.forename: D
authors.initials: D
authors.lastname: Ogreid
authors.forename: A
authors.initials: A
authors.lastname: Berglund
authors.forename: L
authors.initials: L
authors.lastname: Balteskard
authors.forename: J
authors.initials: J
authors.lastname: Ploen
authors.forename: T
authors.initials: T
authors.lastname: Fokstuen
authors.forename: H
authors.initials: H
authors.lastname: Starkhammar
authors.forename: H
authors.initials: H
authors.lastname: Sørbye
authors.forename: K
authors.initials: K
authors.lastname: Tveit
authors.forename: P
authors.initials: P
authors.lastname: Pfeiffer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010071:Oxaloacetates; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin