Irinotecan-Cetuximab-Bevacizumab as a Salvage Treatment in Heavily Pretreated Metastatic Colorectal Cancer Patients: A Retrospective Observational StudyFeliu Batlle J.a · Cuadrado E.b · Castro J.a · Caldés T.b · Belda C.a · Sastre J.b · Barriuso J.a · Martínez Marín V.a · Díaz-Rubio E.b · González-Barón M.a
aMedical Oncology Department, Hospital Universitario La Paz, and bMedical Oncology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background: The objective was to evaluate the efficacy of irinotecan-cetuximab-bevacizumab in combination as a salvage treatment for heavily pretreated metastatic colorectal cancer patients. Methods: A total of 39 patients resistant to both oxaliplatin and irinotecan were included in this retrospective study. Treatment consisted of irinotecan 180/m2 every 14 days, weekly cetuximab standard dose and bevacizumab 5 mg/kg every 14 days. Results: Partial response was observed in 8 patients (20%), stable disease in 24 (61%) and progressive disease in 7 (18%). Overall response rate in KRAS wild type was 6/22 (27%) and in mutated KRAS it was 2/15 (13%). Median time to progression was 8 months (6.4–9.4) and median overall survival 12 months (10.1–13.8). Overall, grade 3–4 adverse events were observed in 24 patients (62%). Conclusions: This regimen is active and moderately well tolerated in heavily pretreated advanced colorectal patients. However, caution is advisable when interpreting these results, because they run against the findings of two large phase III trials.
© 2011 S. Karger AG, Basel
- Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74–108.
- Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–2342.
- Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008;26:2013–2019.
- Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D’Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408–1417.
- Saltz LB, Lenz HJ, Kindler HL, Hochster HS, Wadler S, Hoff PM, Kemeny NE, Hollywood EM, Gonen M, Quinones M, Morse M, Chen HX: Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 2007;25:4557–4561.
- Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–345.
- Roca JM, Alonso V, Pericay C, Escudero P, Salud A, Losa F, López LJ, Guasch I, Méndez M, Quintero-Aldana G, Grande C, Vicente P, Arrivi A, Martin C, Moreno I, García P, Antón I, Constenla M, Yubero A, Cirera L: Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer. Chemotherapy 2010;56:142–146.
- Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kroning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd: EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:2311–2319.
- Riedel F, Gotte K, Li M, Hormann K, Grandis JR: EGFR antisense treatment of human HNSCC cell lines down-regulates VEGF expression and endothelial cell migration. Int J Oncol 2002;21:11–16.
- Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM, Rak J, Kerbel RS: Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis. Cancer Res 2001;61:5090–5101.
- Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, van Groeningen CJ, Sinnige HA, Richel DJ, Voest EE, Dijkstra JR, Vink-Borger ME, Antonini NF, Mol L, van Krieken JH, Dalesio O, Punt CJ: Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 2009;360:563–572.
- Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D, Marshall J, Cohn A, McCollum D, Stella P, Deeter R, Shahin S, Amado RG: A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol 2009;27:672–680.
- Mayer RJ: Targeted therapy for advanced colorectal cancer – more is not always better. N Engl J Med 2009;360:623–625.
- Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–216.
- Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, JuanT, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD: Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:1626–1634.
- Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P: Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 2009;27:663–671.
- Grothey A: Is there a third-line therapy for metastatic colorectal cancer? Semin Oncol 2006;33:S36–S38.
- Meriggi F, Di Biasi B, Caliolo C, Zaniboni A: The potential role of pemetrexed in gastrointestinal cancer. Chemotherapy 2008;54:1–8.
Segal NH, Reidy-Lagunes D, Capanu M, Kemeny N, Chung K, Kelsen E, Hollywood E, Goodman-Davis N, Saltz LB: Phase II study of bevacizumab in combination with cetuximab plus irinotecan in irinotecan-refractory colorectal cancer (CRC) patients who have progressed on a bevacizumab-containing regimen (The BOND 2.5 Study) (abstract). Proc Am Soc Clin Oncol 2009;27:4087.
Ciardiello F, Troiani T, Bianco R, Orditura M, Morgillo F, Martinelli E, Morelli MP, Cascone T, Tortora G: Interaction between the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor (VEGF) pathways: a rational approach for multi-target anticancer therapy. Ann Oncol 2006;17(suppl 7):vii109–vii114.
- Chen HX, Mooney M, Boron M, Vena D, Mosby K, Grochow L, Jaffe C, Rubinstein L, Zwiebel J, Kaplan RS: Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol 2006;24:3354–3360.
- Jhawer M, Goel S, Wilson AJ, Montagna C, Ling YH, Byun DS, Nasser S, Arango D, Shin J, Klampfer L, Augenlicht LH, Perez-Soler R, Mariadason JM: PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res 2008;68:1953–1961.
- Staal S, O’Connell MJ, Allegra CJ: The marriage of growth factor inhibitors and chemotherapy: bliss or bust? J Clin Oncol 2009;27:1545–1548.
- Vigneron A, Gamelin E, Coqueret O: The EGFR-STAT3 oncogenic pathway up-regulates the Eme1 endonuclease to reduce DNA damage after topoisomerase I inhibition. Cancer Res 2008;68:815–825.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.