title: Outcome of second-line treatment after first-line chemotherapy with the GONO FOLFOXIRI regimen.
abstract: OBJECTIVE
  FOLFOXIRI demonstrated higher efficacy compared to 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) as first-line treatment of metastatic colorectal cancer. We evaluated the outcome of second-line treatments among 196 patients treated with first-line FOLFOXIRI in three consecutive trials conducted by the Gruppo Oncologico Nord Ovest group.
  
  
  METHODS
  One hundred seventy-two of 196 patients so far progressed and 136 (79%) received second-line therapies: 32 (24%) were rechallenged with FOLFOXIRI, 52 (38%) were treated with irinotecan- or oxaliplatin-based doublets, and 52 (38%) received fluoropyrimidine plus mytomicin C or single-agent chemotherapy. Only 10 patients received bevacizumab (3) or cetuximab (7) with chemotherapy. Activity and efficacy data were collected and subgroup analyses were performed according to the regimen administered.
  
  
  RESULTS
  Overall response rate (RR) was 23%; median progression-free survival (PFS) and overall survival (OS) were 5.9 and 13.2 months, respectively. At an exploratory subgroup analysis, retreatment with FOLFOXIRI was associated with longer PFS (8.2 versus 6.3 months; P = .003, hazard ratio [HR] = 0.61) and OS (19.3 versus 14.0 months; P = .02, HR = 0.57) compared with doublets; single-agent chemotherapy or fluoropyrimidine plus mytomicin C was significantly lower in terms of RR (8%), PFS (3.0 months), and OS (8.7 months) compared with FOLFOXIRI or doublets.
  
  
  CONCLUSIONS
  First-line FOLFOXIRI does not impair the efficacy of second-line treatments. In some patients rechallenge with FOLFOXIRI may represent a valid option, although potential imbalances in prognostic factors due to better patient selection should be considered.
authors: U.O. Oncologia Medica 2 Universitaria, Polo Oncologico Area Vasta Nord-Ovest, Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy.
authors: Lorenzo
authors: L
authors: Fornaro
authors: Enrico
authors: E
authors: Vasile
authors: Gianluca
authors: G
authors: Masi
authors: Fotios
authors: F
authors: Loupakis
authors: Giacomo Giulio
authors: GG
authors: Baldi
authors: Giacomo
authors: G
authors: Allegrini
authors: Lisa
authors: L
authors: Salvatore
authors: Chiara
authors: C
authors: Cremolini
authors: Samanta
authors: S
authors: Cupini
authors: Enrico
authors: E
authors: Cortesi
authors: Alessandro
authors: A
authors: Tuzi
authors: Cristina
authors: C
authors: Granetto
authors: Isa Maura
authors: IM
authors: Brunetti
authors: Sergio
authors: S
authors: Ricci
authors: Alfredo
authors: A
authors: Falcone
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D016685:Mitomycin; D000077146:Irinotecan; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin