title: Efficacy and tolerability of oxaliplatin plus irinotecan 5-fluouracil and leucovorin regimen in advanced stage colorectal cancer patients pretreated with irinotecan 5-fluouracil and leucovorin.
abstract: OBJECTIVE
  Oxaliplatin has been introduced in the treatment of advanced colorectal cancer during the past few years. The pre-existing treatment of leucovorin-5-fluorouracil-irinotecan (IFL), although reasonably effective, has needed novel, active agents to increase the response rate and overall survival. We planned this phase 2 study in patients pretreated with IFL, adding oxaliplatin as second-line treatment: our objectives were to determine response rate and overall survival.
  
  
  METHODS
  All patients (median age 65) were designated to receive 6 cycles of chemotherapy: leucovorin 200 mg/m2 infused for 60 minutes, 5-fluorouracil 500 mg/m2 bolus at 30 minutes from the start of the previous infusion, irinotecan 135 mg/m2 infused for 90 minutes, and oxaliplatin 135 mg/m2 for 90 minutes, infused sequentially on day 1 and repeated every 3 weeks. Standard ondansetron antiemetic treatment and dexamethasone 8 mg were administered to all patients. No prophylactic recombinant human granulocyte colony-stimulating factor was permitted.
  
  
  RESULTS
  Fifty-seven patients were recruited and 54 were evaluable for response, survival, and toxicity. All patients had advanced, inoperable, metastatic disease in the liver and/or lungs, abdominal cavity, and multiple sites. All patients had undergone IFL pretreatment and had no response; 40 had disease progression and 14 had stable disease when entering the present study; 302 chemotherapy cycles (mean 5.92) were administered. There was no treatment delay caused by toxicity (either neutropenia or diarrhea). Irinotecan and oxaliplatin were reduced by 25% in 6 (11.1%) patients. No complete responses were observed; 21 (38.9%) patients achieved partial response, 26 (48.2%) had stable disease, and 7 (13%) had disease progression. Median duration of response was 6 months, time to tumor progression (TTP) 8 months, and median overall survival after the initiation of second-line treatment was 10 months (95% confidence interval [CI], 7.5-12.6).
  
  
  CONCLUSIONS
  The addition of oxaliplatin to IFL as second-line treatment rendered a prolongation of survival and a response rate of 38.9% in patients in whom IFL pretreatment had failed.
authors.affiliation: First Oncology Dept, Errikos Dunant Hospital, Athens, Greece. dr-gps@ath.forthnet.gr
authors.forename: George P
authors.initials: GP
authors.lastname: Stathopoulos
authors.forename: Sotiris K
authors.initials: SK
authors.lastname: Rigatos
authors.forename: John G
authors.initials: JG
authors.lastname: Stathopoulos
authors.forename: John P
authors.initials: JP
authors.lastname: Xynotroulas
authors.forename: Evangelini
authors.initials: E
authors.lastname: Dimou
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D003907:Dexamethasone; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin