title: Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial.
abstract: BACKGROUND
  This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy.
  
  
  METHODS
  In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity.
  
  
  RESULTS
  Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%).
  
  
  CONCLUSIONS
  The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).
authors.affiliation: Medical Oncology Department, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: E
authors.initials: E
authors.lastname: Samalin
authors.affiliation: Medical Oncology Department, Hôpital Robert Debré, 51092 Reims, France.
authors.forename: O
authors.initials: O
authors.lastname: Bouché
authors.affiliation: Biostatistics Department, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Thézenas
authors.affiliation: Medical Oncology Department, Centre Antoine-Lacassagne, 06189 Nice, France.
authors.forename: E
authors.initials: E
authors.lastname: Francois
authors.affiliation: Medical Oncology Department, Centre Oscar Lambret, 59000 Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Adenis
authors.affiliation: Medical Oncology Department, Institut de cancérologie de l'Ouest, 44805 Saint Herblain, France.
authors.forename: J
authors.initials: J
authors.lastname: Bennouna
authors.affiliation: Medical Oncology Department, Assistance Publique des Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Taieb
authors.affiliation: Medical Oncology Department, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Desseigne
authors.affiliation: Digestive Oncology Department Assistance Publique des Hôpitaux de Marseille, La Timone, Université de Marseille, 13005 Marseille, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Seitz
authors.affiliation: Medical Oncology Department, Centre Alexis Vautrin, 54519 Vandœuvre-lès-Nancy, France.
authors.forename: T
authors.initials: T
authors.lastname: Conroy
authors.affiliation: Medical Oncology Department, Centre François Baclesse, 14000 Caen, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Galais
authors.affiliation: Medical Oncology Department, Hôpital Saint Eloi, CHRU Montpellier, 34295 Montpellier, France.
authors.forename: E
authors.initials: E
authors.lastname: Assenat
authors.affiliation: Translational Research Unit, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: E
authors.initials: E
authors.lastname: Crapez
authors.affiliation: Pharmacology Department, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: S
authors.initials: S
authors.lastname: Poujol
authors.affiliation: Pathology Department, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Bibeau
authors.affiliation: Pathology Department, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Boissière
authors.affiliation: Biochemistry Department, Hôpital Européen Georges Pompidou, 75015 Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Medical Oncology Department, Institut du Cancer de Montpellier, 34298 Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Ychou
authors.affiliation: Medical Oncology Department, Hôpital Saint Eloi, CHRU Montpellier, 34295 Montpellier, France.
authors.forename: T
authors.initials: T
authors.lastname: Mazard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D000077157:Sorafenib; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D010671:Phenylurea Compounds; D011518:Proto-Oncogene Proteins; D009536:Niacinamide; D000077146:Irinotecan; D000077157:Sorafenib; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002166:Camptothecin