Biweekly cetuximab and first-line chemotherapy in chinese patients with k-ras
wild-type colorectal cancers

Wing-Lok Chan; Victor Ho Fun Lee; Wai Kwan Steven Siu; Pui Ying Patty Ho; Rico King Yin Liu; To Wai Leung

doi:10.4103/2278-330X.136802

View/Download PDF

Buy Reprints

PDF

Translate this page into:

COLORECTAL CANCER : Original Article

03 (

); 175-178

doi:

10.4103/2278-330X.136802

Biweekly cetuximab and first-line chemotherapy in chinese patients with k-ras wild-type colorectal cancers

Wing-Lok Chan^1,, Victor Ho Fun Lee², Wai Kwan Steven Siu¹, Pui Ying Patty Ho¹, Rico King Yin Liu¹, To Wai Leung¹

1 Departments of Clinical Oncology, Queen Mary Hospital, Hong Kong, China

2 The University of Hong Kong, Hong Kong, China

*Corresponding author: Dr. Wing-Lok Chan. cwl088@ha.org.hk

Published: 2020-12-31

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Licence

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Disclaimer:
This article was originally published by Thieme Medical and Scientific Publishers Pvt. Ltd. and was migrated to Scientific Scholar after the change of Publisher.

Abstract

Background: The efficacy and safety of using combination chemotherapy with cetuximab as first-line treatment in patients with K-ras wild-type colorectal cancers has been well established. In general, weekly cetuximab was given with biweekly chemotherapy FOLFOX-4 or FOLFIRI, synchronizing them would be appealed to both patients and health care professionals. Materials and Methods: This Phase II, prospective study investigated the efficacy and safety of using biweekly cetuximab 500 mg/m ² with chemotherapy FOLFOX-4 or FOLFIRI as first-line treatment for Chinese patients with K-ras wild-type metastatic colorectal cancer. The study endpoints included overall objective response (OR), progression-free survival (PFS), overall survival (OS) and safety. Results: Total 15 Chinese patients (male: 10 [67%]; median age: 60 [range 41-80]) were enrolled. Patients received median 12 cycles (range 2-12) of chemotherapy + cetuximab (FOLFOX-4 + cetuximab: 9 [60%]; FOLFIRI + cetuximab: 6 [40%]). Six patients (40%) with non-progressive disease after 12 cycles of chemotherapy + cetuximab carried on maintenance cetuximab. Median duration of follow-up (FU) was 23.7 months. The OR was 40% (complete response: 0%; partial response: 40%) for a disease control rate of 87%. Median PFS and OS were 7.8 months and 17.9 months respectively. For maintenance cetuximab phase, median PFS since the start of maintenance cetuximab was 6.8 months and median OS was 17.0 months. The only grade 3-4 toxicities were neutropenia (26.7%) in chemotherapy phase and acneiform rashes (16.7%) in maintenance phase. Conclusions: Biweekly cetuximab with combination chemotherapy was effective and safe as weekly dose. Further studies are warranted for the role of maintenance cetuximab.

Keywords

References

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.
Lea IA, Jackson MA, Li X, Bailey S, Peddada SD, Dunnick JK. Genetic pathways and mutation profiles of human cancers: Site- and exposure-specific patterns. Carcinogenesis 2007;28:1851-8.
Normanno N, Tejpar S, Morgillo F, De Luca A, Van Cutsem E, Ciardiello F. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol 2009;6:519-27.
De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008;19:508-15.
Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 2007;96:1166-9.
Lièvre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008;26:374-9.
Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006;66:3992-5.
Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408-17.
Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: The OPUS study. Ann Oncol 2011;22:1535-46.
Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: Updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011;29:2011-9.
Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 2012;48:1466-75.
Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial. Lancet 2011;377:2103-14.
De Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938-47.
Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: A multicentre randomised trial. Lancet 2000;355:1041-7.
Tabernero J, Pfeiffer P, Cervantes A. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: An effective, more convenient alternative to weekly administration? Oncologist 2008;13:113-9.
Delbaldo C, Pierga JY, Dieras V, Faivre S, Laurence V, Vedovato JC, et al. Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Eur J Cancer 2005;41:1739-45.
Tabernero J, Ciardiello F, Rivera F, Rodriguez-Braun E, Ramos FJ, Martinelli E, et al. Cetuximab administered once every second week to patients with metastatic colorectal cancer: A two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol 2010;21:1537-45.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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;92:205-16.
Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005;7:301-11.
Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 2007;98:1275-80.
Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer 2007;120:781-7.

Fulltext Views
22

PDF downloads
7

View/Download PDF
Download Citations

BibTeX
RIS

Show Sections

[1] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.

[2] Lea IA, Jackson MA, Li X, Bailey S, Peddada SD, Dunnick JK. Genetic pathways and mutation profiles of human cancers: Site- and exposure-specific patterns. Carcinogenesis 2007;28:1851-8.

[3] Normanno N, Tejpar S, Morgillo F, De Luca A, Van Cutsem E, Ciardiello F. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol 2009;6:519-27.

[4] De Roock W, Piessevaux H, De Schutter J, Janssens M, De Hertogh G, Personeni N, et al. KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 2008;19:508-15.

[5] Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 2007;96:1166-9.

[6] Lièvre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008;26:374-9.

[7] Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 2006;66:3992-5.

[8] Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408-17.

[9] Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: The OPUS study. Ann Oncol 2011;22:1535-46.

[10] Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: Updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011;29:2011-9.

[11] Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, et al. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer 2012;48:1466-75.

[12] Maughan TS, Adams RA, Smith CG, Meade AM, Seymour MT, Wilson RH, et al. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: Results of the randomised phase 3 MRC COIN trial. Lancet 2011;377:2103-14.

[13] De Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18:2938-47.

[14] Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: A multicentre randomised trial. Lancet 2000;355:1041-7.

[15] Tabernero J, Pfeiffer P, Cervantes A. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: An effective, more convenient alternative to weekly administration? Oncologist 2008;13:113-9.

[16] Delbaldo C, Pierga JY, Dieras V, Faivre S, Laurence V, Vedovato JC, et al. Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma. Eur J Cancer 2005;41:1739-45.

[17] Tabernero J, Ciardiello F, Rivera F, Rodriguez-Braun E, Ramos FJ, Martinelli E, et al. Cetuximab administered once every second week to patients with metastatic colorectal cancer: A two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol 2010;21:1537-45.

[18] Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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;92:205-16.

[19] Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM. Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 2005;7:301-11.

[20] Kimura H, Sakai K, Arao T, Shimoyama T, Tamura T, Nishio K. Antibody-dependent cellular cytotoxicity of cetuximab against tumor cells with wild-type or mutant epidermal growth factor receptor. Cancer Sci 2007;98:1275-80.

[21] Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer 2007;120:781-7.

Biweekly cetuximab and first-line chemotherapy in chinese patients with k-ras wild-type colorectal cancers

Abstract

Abstract

Keywords

References

Suggested read for related articles:

We value your privacy