title: Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer.
abstract: BACKGROUND
  This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer.
  
  
  METHODS
  Seventy-four patients with measurable disease and a WHO performance status of 2 or less were treated with irinotecan 210 mg/m(2) as a 30-90 min intravenous infusion on day 1, followed by 5-FU 500 mg/m(2) and FA 60 mg/m(2) bolus on days 1 and 2, every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was the objective response rate.
  
  
  RESULTS
  Twenty-nine out of 68 evaluable patients achieved a complete (n = 7) or partial (n = 22) response, leading to an overall response rate of 43% [95% confidence interval (CI) 31% to 55%]. The median duration of response was 10 months. The estimated median time to progression and survival were 6.4 months (95% CI 5.4-9.0) and 15.6 months (95% CI 13.3-19.0), respectively, in the intention-to-treat population. A total of 860 cycles were administered to 74 patients. Neutropenia was the main adverse event with grade 3-4 toxicity in 66% of patients and 17.5% of cycles. Grade 3-4 non-haematological toxicities were infrequent and included diarrhoea in 16% of patients and 2% of cycles and nausea/vomiting in 10% of patients and 1% of cycles.
  
  
  CONCLUSIONS
  Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance. The low incidence of grade 3-4 non-haematological toxicity justifies the further evaluation of this combination in the context of randomised clinical trials.
authors.affiliation: Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Sweden. bengt.glimelius@onkologi.uu.se
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
authors.forename: R
authors.initials: R
authors.lastname: Ristamäki
authors.forename: M
authors.initials: M
authors.lastname: Kjaer
authors.forename: P
authors.initials: P
authors.lastname: Pfeiffer
authors.forename: T
authors.initials: T
authors.lastname: Skovsgaard
authors.forename: K M
authors.initials: KM
authors.lastname: Tveit
authors.forename: T
authors.initials: T
authors.lastname: Linné
authors.forename: J E
authors.initials: JE
authors.lastname: Frödin
authors.forename: B
authors.initials: B
authors.lastname: Boussard
authors.forename: D
authors.initials: D
authors.lastname: Oulid-Aïssa
authors.forename: S
authors.initials: S
authors.lastname: Pyrhönen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001707:Biopsy, Needle; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin