title: Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3.
abstract: PURPOSE The primary objective of this randomized, multicenter, phase III trial was to investigate whether the addition of irinotecan to the de Gramont infusional fluorouracil (FU)/leucovorin (LV) adjuvant regimen (LV5FU2) would improve disease-free survival (DFS) in patients with stage III colon cancer. PATIENTS AND METHODS After curatively intentioned surgery, patients with stage II and III colon cancer were randomly allocated surgery to receive LV5FU2 (LV 200 mg/m(2) as a 2-hour infusion, followed by FU; as a 400 mg/m(2) bolus and then a 600 mg/m(2) continuous infusion over 22 hours, days 1 and 2, every 2 weeks for 12 cycles: de Gramont regimen) with or without irinotecan (180 mg/m(2) as a 30- to 90-minute infusion, day 1, every 2 weeks). In total, 260 (7.9%) of 3,278 patients received an alternative high-dose infusional FU/LV regimen (Arbeitsgemeinschaft Internische Onkologie regimen) with or without irinotecan. Results The principal efficacy analysis was based on 2,094 treated patients with stage III disease, randomly allocated in the LV5FU2 strata. After a median follow-up of 66.3 months, the 5-year DFS rate was 56.7% with irinotecan/LV5FU2 and 54.3% with LV5FU2 alone (primary end point: log-rank P = .106). Combining irinotecan with LV5FU2 did not significantly improve overall survival in this patient group compared with LV5FU2 alone (5-year rate 73.6% v 71.3%, respectively; log-rank P = .094). The addition of irinotecan to LV5FU2 was associated with an increased incidence of grade 3 to 4 GI events and neutropenia. CONCLUSION Irinotecan added to LV5FU2 as adjuvant therapy did not confer a statistically significant improvement in DFS or overall survival in patients with stage III colon cancer compared with LV5FU2 alone.
authors.affiliation: Digestive Oncology Unit, University Hospital Gasthuisberg/Leuven, Herestraat 49, 3000 Leuven, Belgium. Eric.VanCutsem@uz.kuleuven.ac.be
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: György
authors.initials: G
authors.lastname: Bodoky
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
authors.forename: Bernard
authors.initials: B
authors.lastname: Nordlinger
authors.forename: Claire
authors.initials: C
authors.lastname: Topham
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.forename: Alberto F
authors.initials: AF
authors.lastname: Sobrero
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
authors.forename: Laura
authors.initials: L
authors.lastname: Cisar
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Khayat
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Arnaud D
authors.initials: AD
authors.lastname: Roth
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin