title: Intensive systemic chemotherapy combined with surgery for metastatic colorectal cancer: results of a phase II study.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of the metastatic irinotecan plus oxaliplatin (MIROX) strategy (adjuvant FOLFOX-7 followed by FOLFIRI), in patients with resectable metastatic colorectal cancer.
  
  
  METHODS
  Forty-seven patients with resectable metastases of colorectal cancer were prospectively enrolled onto this study. Treatment consisted of six cycles of leucovorin 400 mg/m(2), oxaliplatin 130 mg/m(2) in a 120-minute infusion, and fluorouracil (FU) 2,400 mg/m(2) in a 46-hour infusion, every 2 weeks (FOLFOX-7), followed by six cycles of leucovorin 400 mg/m(2), irinotecan 180 mg/m(2) in a 90-minute infusion, bolus FU 400 mg/m(2), and FU 2,400 mg/m(2) as a 46-hour infusion, every 2 weeks (FOLFIRI). Surgery was performed before chemotherapy in 25 patients and after six cycles of FOLFOX-7 in 22 patients (six cycles of FOLFIRI were administered after surgery).
  
  
  RESULTS
  All but one of the patients underwent curative surgery. Two patients refused postoperative chemotherapy. Tolerability was generally good. The main toxicities were grade 3 to 4 neutropenia (13%) and thrombocytopenia (11%); no febrile neutropenia or bleeding occurred, and there were no deaths caused by toxicity. Two pathologically confirmed complete responses and 15 partial responses were obtained with FOLFOX-7 in the 22 patients who received this regimen before surgery (overall response rate, 77%; 95% CI, 68 to 86). The median disease-free survival time was 21 months; the median overall survival has not yet been reached. The 2-year overall and disease-free survival rates were 89% and 47%, respectively.
  
  
  CONCLUSIONS
  The MIROX strategy is feasible and well tolerated by patients with resectable metastatic colorectal cancer. Progression-free and overall survival rates are promising, with a median of 38 months of follow-up. This strategy currently is being compared with the leucovorin and FU regimen in a phase III trial.
authors.affiliation: Service d'hépatogastroentérologie, Groupe Hospitalier Pitié Salpétrière, 47-83 Boulevard de l'hôpital, 75013 Paris, France. jtaieb@club-internet.fr
authors.forename: Julien
authors.initials: J
authors.lastname: Taïeb
authors.forename: Pascal
authors.initials: P
authors.lastname: Artru
authors.forename: François
authors.initials: F
authors.lastname: Paye
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perez
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.forename: Brice
authors.initials: B
authors.lastname: Gayet
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.forename: Frédérique Maindrault
authors.initials: FM
authors.lastname: Goebel
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.forename: Rolland
authors.initials: R
authors.lastname: Parc
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin