Published 2014
| Version v1
Journal article
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
Contributors
Others:
- CRLCC Val d'Aurelle - Paul Lamarque
- Hôpital universitaire Robert Debré [Reims]
- Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)
- Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille) ; Université de Lille-UNICANCER
- Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO) ; UNICANCER
- CIC - HEGP (CIC 1418) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Centre Léon Bérard [Lyon]
- Hôpital de la Timone [CHU - APHM] (TIMONE)
- Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL) ; UNICANCER
- Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC) ; Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)
- Institut de Génétique Moléculaire de Montpellier (IGMM) ; Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
- Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1) ; Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
- CRLC Val d'Aurelle-Paul Lamarque ; CRLCC Val d'Aurelle - Paul Lamarque
- Hôpital Européen Georges Pompidou [APHP] (HEGP) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Description
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%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).
Abstract
IMPACT: 5.922Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.umontpellier.fr/hal-02181353
- URN
- urn:oai:HAL:hal-02181353v1
Origin repository
- Origin repository
- UNICA