title: A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer.
abstract: BACKGROUND
  Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially reduced toxicity.
  
  
  METHODS
  One hundred and forty-one patients with unresectable mCRC were enrolled in a randomized study comparing standard XELOX (XELOX(30)), arm A, and XELOX(30Chron), arm B-both with short-time infusion of oxaliplatin-with the primary aim of reducing overall toxicity.
  
  
  RESULTS
  Overall toxicity grade 2-4 was 90% versus 85%, P = 0.47 and grade 3-4 was 31% versus 37%, P = 0.6 in arm A and B, respectively. We found no significant differences in median overall survival (17.6 versus 15.5 months; P = 0.068) and median progression-free survival (8.9 versus 8.8 months; P = 0.7). The incidence of grade 3 neuropathy was 16% in arm A and 19% in arm B (P = 0.7) after a cumulative dose of oxaliplatin of 1000 mg/m(2).
  
  
  CONCLUSIONS
  XELOX(30Chron) does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy.
authors.affiliation: Department of Oncology, Odense University Hospital, Sonder Boulevard 29, DK-5000 Odense C, Denmark. camilla.qvortrup@ouh.regionsyddanmark.dk
authors.forename: C
authors.initials: C
authors.lastname: Qvortrup
authors.forename: B V
authors.initials: BV
authors.lastname: Jensen
authors.forename: T
authors.initials: T
authors.lastname: Fokstuen
authors.forename: S E
authors.initials: SE
authors.lastname: Nielsen
authors.forename: N
authors.initials: N
authors.lastname: Keldsen
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
authors.forename: B
authors.initials: B
authors.lastname: Bjerregaard
authors.forename: J
authors.initials: J
authors.lastname: Mejer
authors.forename: F O
authors.initials: FO
authors.lastname: Larsen
authors.forename: P
authors.initials: P
authors.lastname: Pfeiffer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D055870:Drug Chronotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010071:Oxaloacetates
chemical_list: D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil