Share This Article:

Survival Outcome in Metastatic Colorectal Cancer Patients Treated with Bevacizumab Followed by Cetuximab

Full-Text HTML Download Download as PDF (Size:399KB) PP. 263-269
DOI: 10.4236/ijcm.2012.34052    3,112 Downloads   4,913 Views  

ABSTRACT

Background: Molecular targeted agents, such as bevacizumab and cetuximab, have been shown to improve the overall survival of metastatic colorectal cancer (mCRC) patients. However, we still do not know the best sequence in which to use the molecular targeted agents for mCRC, especially in K-ras wild-type cases. Methods: From July 2006 to November 2010, 63 chemotherapy-naive patients who were diagnosed with mCRC and received an oxaliplatin-based regimen as the first line, did not respond to a bevacizumab-containing regimen used as the first or second line, and received cetuximab or continued bevacizumab, were eligible for this analysis. Thirty-two patients received cetuximab as the third or fourth line chemotherapy due to the K-ras wild-type (Group A). Also, thirty-one patients continued a bevacizumab-containing regimen in spite of disease progression (Group B). Results: The difference in the rate of serious adverse events was not significant between the two groups, but the rate of overall adverse events tended to be higher in Group A than in Group B. The median overall survival (MST) was significantly higher in Group A than Group B (30.8 months and 23.13 months (95%CI: 15.80 - 30.47), respectively) (P = 0.031). Group A patients were all K-ras wild-type, and 21 of Group B were K-ras mutant type. Compared with Group B patients with the K-ras mutant type, MST of Group A patients was significantly longer (30.8 months and 25.73 months, respectively) (P = 0.025). Conclusion: Using cetuximab after progression with bevacizumab might be an effective sequence to improve the overall survival of K-ras wild-type mCRC patients. However, we need further prospective studies to identify the best sequence of chemotherapy for mCRC patients.

Cite this paper

K. Kataoka, A. Kanazawa, A. Nakajima, H. Hosogi, S. Kanaya, T. Nagasaka and Y. Kono, "Survival Outcome in Metastatic Colorectal Cancer Patients Treated with Bevacizumab Followed by Cetuximab," International Journal of Clinical Medicine, Vol. 3 No. 4, 2012, pp. 263-269. doi: 10.4236/ijcm.2012.34052.

References

[1] H. Hurwitz, L. Fehrenbacher, W. Novotny, et al., “Bevacizumab Plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer,” New England Journal of Medicine, Vol. 350, 2004, pp. 2335-2342. doi:10.1056/NEJMoa032691
[2] F. F. Kabbinavar, J. Hambleton, R. D. Mass, et al., “Combined Analysis of Efficacy: The Addition of Bevacizumab to Fluoroura-cil/Leucovorin Improves Survival for Patients with Me-tastatic Colorectal Cancer,” Journal of Clinical Oncology, Vol. 23, 2005, pp. 3706- 3712. doi:10.1200/JCO.2005.00.232
[3] L. B. Saltz, S. Clarke, E. Díaz-Rubio, et al., “Bevacizumab in Combination with Oxaliplatin-Based Chemotherapy as First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study,” Journal of Clinical Oncology, Vol. 26, 2008, pp. 2013-2019. doi:10.1200/JCO.2007.14.9930
[4] D. J. Jonker, C. J. O’Callaghan, C. S. Karapetis, et al., “Cetuximab for the Treatment of Colorectal Cancer,” New England Journal of Medicine, Vol. 357, 2007, pp. 2040-2048. doi:10.1056/NEJMoa071834
[5] D. Cunningham, Y. Humblet, S. Siena, et al., “Cetuximab Monotherapy and Cetuximab Plus Irinotecan in Irinotecan Refractory Metastatic Colorectal Cancer,” New England Journal of Medicine, Vol. 351, No. 4, 2004, pp. 337-345. doi:10.1056/NEJMoa033025
[6] W. De Roock, H. Piessevaux, J. De Schutter, et al., “K-ras Wild-Type State Predicts Survival and Is Associated to Early Radiological Response in Metastatic Colorectal Cancer Treated with Cetuximab,” Annals of Oncology, Vol. 19, No. 3, 2008, pp. 508-515. doi:10.1093/annonc/mdm496
[7] A. Lievre, J. B. Bachet, V. Boige, et al., “K-ras Mutations as an Independent Prognostic Factor in Patients with Advanced Colorectal Cancer Treated with Cetuximab,” Journal of Clinical Oncology, Vol. 26, 2008, pp. 374- 379. doi:10.1200/JCO.2007.12.5906
[8] C. S. Karpatis, S. Khambata-Ford, D. J. Jonker, et al., “K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer,” New England Journal of Medicine, Vol. 359, No. 17, 2008, pp. 1757-1765. doi:10.1056/NEJMoa0804385
[9] C. Bokemeyer, I. Bondarenko, J. T. Hartmann, et al., “K-ras Status and Efficacy of First-Line Treatment of Patients with Metastatic Colorectal Cancer (mCRC) with FOLFOX with or without Cetuximab: The OPUS Experience,” Journal of Clinical Oncology, Vol. 26, Suppl. 178, 2008.
[10] E. Van Cutsem, I. Lang, G. Dfhaens, et al., “K-ras Status and Efficacy in the Firstline Treatment of Patients with Metastatic Colorectal Cancer (mCRC) Treated with FOLFIRI with or without Cetuximab: The CRYSTAL Experience,” Journal of Clinical Oncology, Vol. 26, Suppl. 5, 2008.
[11] A. Grothey, M. Sugrue, D. Purdie, et al., “Bevacizumab beyond First Progression Is Associated with Prolonged Overall Survival in Metastatic Colorectal Cancer: Results from a Large Observational Cohort Study (BRiTE),” Journal of Clinical Oncology, Vol. 26, No. 35, 2008, pp. 5326-5334. doi:10.1200/JCO.2008.16.3212
[12] A. L. Cohn, T. Bekaili-Saab, J. C. Bedcell, et al., “Clinical Outcomes in Bevacizumb (BV)-Treated Patients (pts) with Metastatic Colorectal Cancer (mCRC): Results from ARIES Observational Cohort Study (OCS) and Confir-mation of BRiTE Data on BV beyond Progression (BBP),” Journal of Clinical Oncology, Vol. 28, No. 15, 2010, Abstract 3596.
[13] L. M. Ellis, “Epidermal Growth Factor Receptor in Tumor Angiogenesis,” Hematology/Oncology Clinics of North America, Vol. 18, 2004, pp. 1007-1021. doi:10.1016/j.hoc.2004.06.002
[14] A. Viloria-Petit, T. Crombet, S. Jothy, et al., “Acquired Resistance to the Antitumor Effect of Epidermal Growth Factor Receptor-Blocking Antibodies in Vivo: A Role for Altered Tumor Angiogenesis,” Cancer Research, Vol. 61, 2001, pp. 5090-5101.
[15] E. Norguet, L. Dahan, J. Gaudart, et al., “Cetuximab after Bevacizumab in Metastatic Colorectal Cancer: Is It the Best Sequence?” Digestive and Liver Disease, Vol. 43, No. 11, 2011, pp. 917-919. doi:10.1016/j.dld.2011.06.002
[16] P. Therasse, S. G. Arbuck, E. A. Eisenhauer, et al., “New Guidelines to Evaluate the Response to Treatment in Solid Tumors,” Journal of the National Cancer Institute, Vol. 92, No. 3, 2000, pp. 205-216. doi:10.1093/jnci/92.3.205
[17] L. B. Saltz, H. J. Lenz, H. L. Kindler, et al., “Randomized Phase II Trial of Cetuximab, Bevacizumab, and Irinotecan Compared with Cetuximab and Bevacizumab Alone in Irinotecanrefractory Colorectal Cancer: The BOND-2 Study,” Journal of Clinical Oncology, Vol. 25, No. 3, 2007, pp. 4557-4561. doi:10.1200/JCO.2007.12.0949
[18] J. Tol, M. Koopman, C. J. Rodenburg, et al., “A Randomised Phase III Study on Capecitabine, Oxaliplatin and Bevacizumab with or without Cetuximab in Firstline Advanced Colo-Rectal Cancer, the CAIRO2 Study of the Dutch Colorectal Cancer Group (DCCG): An Interim Analysis of Toxicity,” Annals of Oncology, Vol. 19, 2008, pp. 734-738. doi:10.1093/annonc/mdm607
[19] J. R. Hecht, E. Mitchell, T. Chidiac, et al., “An Updated Analysis of the Safety and Efficacy of Oxaliplatin (Ox)/Bevacizumab (bev) +/? Panitumumab (pmab) for Firstline Treatment (tx) of Metastatic Colorectal Cancer (mCRC) from a Randomized, Controlled Trial (PACCE)”. Program and Abstracts of the 2008 Gastrointestinal Cancers Symposium, Orlando, 25-27 January 2008.
[20] J. R. Hecht, E. Mitchell, T. Chidiac, et al., “Interim Results from PACCE: Irinotecan (Iri)/ Bevacizumab (bev) +/? Panitumumab (pmab) as First-Line Treatment (tx) for Metastatic Colorectal Cancer (mCRC),” Proceedings and abstracts of the 2008 Gastrointestinal Cancers Symposium, Orlando, 25-27 January 2008.
[21] F. Rinaldi, E. George and A. I. Adler, “NICE Guidance on Cetuximab, Bevacizumab, and Panitumumab for Treatment of Metastatic Colorectal Cancer after First-Line Chemotherapy,” Lancet Oncology, Vol. 13, No. 3, 2012, pp. 233-234. doi:10.1016/S1470-2045(12)70044-X
[22] D. J. Ahnen, P. Feigl, G. Quan, et al., “Ki-ras Mutation and p53 Over-expression Predict the Clinical Behavior of Colorectal Cancer: A Southwest Oncology Group Study,” Cancer Research, Vol. 58, No. 6, 1998, pp. 1149-1158.
[23] M. Esteller, S. González, R. A. Risques, et al., “K-ras and p16 Aberrations Confer Poor Prognosis in Human Colorectal Cancer,” Journal of Clinical Oncology, Vol. 19, No. 2, 2001, pp. 299-304.
[24] H. J. Andreyev, A. R. Norman, D. Cunningham, et al., “Kirsten ras Mutations in Patients with Colorectal Cancer: The ‘RASCAL II’ Study,” British Journal of Cancer, Vol. 85, No. 5, 2001, pp. 692-696. doi:10.1054/bjoc.2001.1964
[25] A. Lièvre, J. B. Bachet, V. Boige, et al., “KRAS Mutations as an Independent Prognostic Factor in Patients with Advanced Colorectal Cancer Treated with Cetuximab,” Journal of Clinical Oncology, Vol. 26, 2008, pp. 374- 379. doi:10.1200/JCO.2007.12.5906
[26] H. I. Hurwitz, J. Yi, W. Ince, et al., “The Clinical Benefit of Bevacizumab in Metastatic Colorectal Cancer Is Independent Of K-ras Mutation Status: Analysis of a Phase III Study of Beva-cizumab with Chemotherapy in Previously Untreated Metastatic Colorectal Cancer,” Oncologist, Vol. 14, No. 1, 2009, pp. 22-28. doi:10.1634/theoncologist.2008-0213
[27] E. A. Baka-lakos, W. E. Burak Jr., D. C. Young, et al., “Is Carcino-Embryonic Antigen Useful in the Follow-Up Management of Patients with Colorectal Liver Metastases?” American Journal of Surgery, Vol. 177, No. 1, 1999, pp. 2-6. doi:10.1016/S0002-9610(98)00303-1
[28] R. Adam, H. Bismuth, D. Castaing, et al., “Repeat Hepatectomy for Colorectal Liver Metastases,” Annals of Surgery, Vol. 225, No. 1, 1997, pp. 51-62. doi:10.1097/00000658-199701000-00006

  
comments powered by Disqus

Copyright © 2017 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.