title: Safety and efficacy of irinotecan plus high-dose leucovorin and intravenous bolus 5-fluorouracil for metastatic colorectal cancer: pooled analysis of two consecutive southern Italy cooperative oncology group trials.
abstract: BACKGROUND
  A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin (LV) 250 mg/m2 plus 5-fluorouracil (5-FU) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer (CRC).
  
  
  METHODS
  Individual data of 254 patients were merged, and baseline features potentially affecting overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of severe toxicity were analyzed by univariate and multivariate analyses.
  
  
  RESULTS
  In the pooled series, ORR was 33% (95% confidence interval [CI], 27%-39%). Liver-only disease (47% vs. 25%; P=0.0012) and absence of previous weight loss (38% vs. 20%; P=0.0189) were significantly associated with a higher ORR on the multivariate analysis. Absence of weight loss (hazard ratio, 1.40; 95% CI, 1.02-1.93; P=0.0377) was significantly associated with a longer PFS (7.5 months vs. 6 months). Median OS was 15.1 months (95% CI, 13.5-16.6 months). Primary surgery, good performance status (PS), only one metastatic site, and oxaliplatin-based second-line treatment independently predicted a longer OS. Grade 4 neutropenia was significantly associated with a PS>or=1, whereas risk of grade>or=3 diarrhea was directly related to age and previous weight loss.
  
  
  CONCLUSIONS
  Patients with no weight loss and/or preserved PS and with a limited disease extent appeared to obtain the greatest benefit from our irinotecan/5-FU/LV regimen, with acceptable toxicity. Notably, the regimen was effective and well tolerated by elderly patients. This regimen may represent the rationale for assessing the addition of novel antiangiogenic drugs to the treatment of metastatic CRC.
authors.affiliation: Division of Medical Oncology A, National Tumor Institute, Naples, and Division of Medical Oncology, University Medical School, Cagliari, Italy. pasqualecomella@libero.it
authors.forename: Pasquale
authors.initials: P
authors.lastname: Comella
authors.forename: Bruno
authors.initials: B
authors.lastname: Massidda
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Filippelli
authors.forename: Donato
authors.initials: D
authors.lastname: Natale
authors.forename: Antonio
authors.initials: A
authors.lastname: Farris
authors.forename: Franco
authors.initials: F
authors.lastname: Buzzi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Tafuto
authors.forename: Luigi
authors.initials: L
authors.lastname: Maiorino
authors.forename: Sergio
authors.initials: S
authors.lastname: Palmeri
authors.forename: Luigi
authors.initials: L
authors.lastname: De Lucia
authors.forename: Sergio
authors.initials: S
authors.lastname: Mancarella
authors.forename: Silvana
authors.initials: S
authors.lastname: Leo
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Cataldis
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; 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; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome; D015431:Weight Loss
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin