| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| 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 |
| Creator | Samalin et al. |
| Author | E. Samalin |
| Author | O. Bouche |
| Author | S. Thezenas |
| Author | E. Francois |
| Author | A. Adenis |
| Author | J. Bennouna |
| Author | J. Taieb |
| Author | F. Desseigne |
| Author | J. F. Seitz |
| Author | T. Conroy |
| Author | M. P. Galais |
| Author | E. Assenat |
| Author | E. Crapez |
| Author | S. Poujol |
| Author | F. Bibeau |
| Author | F. Boissiere |
| Author | P. Laurent-Puig |
| Author | M. Ychou |
| Author | T. Mazard |
| 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%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469). |
| Publication | Br J Cancer |
| Volume | 110 |
| Pages | 1148-54 |
| Date | Mar 4 2014 |
| Journal Abbr | British journal of cancer |
| DOI | 10.1038/bjc.2013.813 |
| ISSN | 1532-1827 (Electronic) 0007-0920 (Linking) |
| Tags | *Mutation, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/*therapeutic use, Camptothecin/administration & dosage/analogs & derivatives, clinic, Colorectal Neoplasms/*drug therapy/genetics, Disease Progression, Disease-Free Survival, Female, Humans, Male, Middle Aged, Niacinamide/administration & dosage/analogs & derivatives, Phenylurea Compounds/administration & dosage, Proto-Oncogene Proteins/*genetics, ras Proteins/*genetics |
| Date Added | 2019/05/22 - 09:42:41 |
| Date Modified | 2019/05/22 - 09:47:55 |
| Notes and Attachments | (Note) (Note) 24407191 (Attachment) |
Institut de Recherche en Cancérologie de
