title: Efficacy of treatment with irinotecan and oxaliplatin combination in FU-resistant metastatic colorectal cancer patients.
abstract: OBJECTIVE
  As single agents, irinotecan and oxaliplatin are active in colorectal cancer after fluorouracil (FU)-containing regimen failure. Their synergistic activity and non-overlapping toxicity profile are well documented, but more data are needed to explore their exact sequence. The aim of this study was to evaluate the activity and tolerability of irinotecan followed by oxaliplatin in patients with FU-resistant colorectal cancer.
  
  
  METHODS
  FU resistance was defined as disease progression during or within 6 months of discontinuing first-line or adjuvant FU/leucovorin chemotherapy. The study treatment consisted of irinotecan 150 mg/m(2) on days 1 and 8 followed by oxaliplatin 85 mg/m(2) on day 1 every 3 weeks. In order to improve the safety profile, we changed the schedule during the study to irinotecan 300 mg/m(2) on day 1 and oxaliplatin 85 mg/m(2) on day 2 every 3 weeks.
  
  
  RESULTS
  Of 54 patients treated, the 45 patients with measurable disease were assessed in the efficacy analysis, whereas all patients receiving at least one cycle were evaluated in the safety analysis. Of the patients assessed for efficacy analysis, 19 cases received the first schedule and 26 patients received the second schedule. Twenty-two patients (49%) responded, 10 of the first schedule and 12 of the second schedule group. Stable disease was observed in 35% of all patients. The median response duration was 6.5 months (range 3-10), the median time to progression was 8 months (range 6-10), and the overall survival was 15 months (10-26+). The NCI-CTC grade 3 side effects documented in all of the treated patients were: nausea/vomiting (11%), diarrhea (18%), and neutropenia (7%); grade 4 diarrhea was observed in 2% of patients.
  
  
  CONCLUSIONS
  The combination of irinotecan followed by oxaliplatin combination is well tolerated and highly active in FU-resistant metastatic colorectal cancer patients.
authors.affiliation: Department of Medical Oncology Unit B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. emilio.bajetta@istitutotumori.mi.it
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.forename: Elena
authors.initials: E
authors.lastname: Beretta
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.forename: Diego
authors.initials: D
authors.lastname: Cortinovis
authors.forename: Erminia
authors.initials: E
authors.lastname: Ferrario
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Dognini
authors.forename: Luisa
authors.initials: L
authors.lastname: Toffolatti
authors.forename: Roberto
authors.initials: R
authors.lastname: Buzzoni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin