Cetuximab is associated with excessive toxicity when combined with bevacizumab plus mFOLFOX6 in metastatic colorectal carcinoma

Allyson J. Ocean, Blase Polite, Paul Christos, Lisa Horvath, Anne Hamilton, Daniel Matulich, Helen X. Chen, Joseph A. Sparano, Hedy L. Kindler

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/leucovorin/oxaliplatin) as first-line therapy for mCRC. Patients and Methods: Sixty-six patients received cetuximab (400 mg/m2 loading dose, then 250 mg/m2 weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity. Results: The most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity. Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase III trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalClinical Colorectal Cancer
Volume9
Issue number5
DOIs
StatePublished - Dec 1 2010

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Colorectal Neoplasms
oxaliplatin
Leucovorin
Drug Therapy
Fluorouracil
Disease Progression
Therapeutics
Cetuximab
Bevacizumab
Exanthema
Venous Thrombosis
Fatigue
Diarrhea
Safety

Keywords

  • KRAS mutation
  • Oxaliplatin
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Cetuximab is associated with excessive toxicity when combined with bevacizumab plus mFOLFOX6 in metastatic colorectal carcinoma. / Ocean, Allyson J.; Polite, Blase; Christos, Paul; Horvath, Lisa; Hamilton, Anne; Matulich, Daniel; Chen, Helen X.; Sparano, Joseph A.; Kindler, Hedy L.

In: Clinical Colorectal Cancer, Vol. 9, No. 5, 01.12.2010, p. 290-296.

Research output: Contribution to journalArticle

Ocean, AJ, Polite, B, Christos, P, Horvath, L, Hamilton, A, Matulich, D, Chen, HX, Sparano, JA & Kindler, HL 2010, 'Cetuximab is associated with excessive toxicity when combined with bevacizumab plus mFOLFOX6 in metastatic colorectal carcinoma', Clinical Colorectal Cancer, vol. 9, no. 5, pp. 290-296. https://doi.org/10.3816/CCC.2010.n.042
Ocean, Allyson J. ; Polite, Blase ; Christos, Paul ; Horvath, Lisa ; Hamilton, Anne ; Matulich, Daniel ; Chen, Helen X. ; Sparano, Joseph A. ; Kindler, Hedy L. / Cetuximab is associated with excessive toxicity when combined with bevacizumab plus mFOLFOX6 in metastatic colorectal carcinoma. In: Clinical Colorectal Cancer. 2010 ; Vol. 9, No. 5. pp. 290-296.
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abstract = "Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/leucovorin/oxaliplatin) as first-line therapy for mCRC. Patients and Methods: Sixty-six patients received cetuximab (400 mg/m2 loading dose, then 250 mg/m2 weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity. Results: The most common grade 3-4 events included diarrhea (14{\%}), fatigue (14{\%}), neuropathy (12{\%}), venous thrombosis (9{\%}), acneiform rash (8{\%}), and desquamation (8{\%}). A protocol-defined prohibitive adverse event occurred in 4 patients (6{\%}), including 2 treatment-associated deaths. Thirty-seven patients (56{\%}) discontinued therapy before disease progression because of either toxicity (n = 19; 29{\%}) or patient withdrawal (n = 18; 27{\%}). Twenty-eight of 37 patients (76{\%}) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity. Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase III trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.",
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T1 - Cetuximab is associated with excessive toxicity when combined with bevacizumab plus mFOLFOX6 in metastatic colorectal carcinoma

AU - Ocean, Allyson J.

AU - Polite, Blase

AU - Christos, Paul

AU - Horvath, Lisa

AU - Hamilton, Anne

AU - Matulich, Daniel

AU - Chen, Helen X.

AU - Sparano, Joseph A.

AU - Kindler, Hedy L.

PY - 2010/12/1

Y1 - 2010/12/1

N2 - Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/leucovorin/oxaliplatin) as first-line therapy for mCRC. Patients and Methods: Sixty-six patients received cetuximab (400 mg/m2 loading dose, then 250 mg/m2 weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity. Results: The most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity. Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase III trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.

AB - Background: The bevacizumab-cetuximab combination has shown promising activity in chemotherapy-refractory metastatic colorectal cancer (mCRC). We sought to determine the safety and efficacy of cetuximab added to bevacizumab plus standard mFOLFOX6 (modified 5-fluorouracil [5-FU]/leucovorin/oxaliplatin) as first-line therapy for mCRC. Patients and Methods: Sixty-six patients received cetuximab (400 mg/m2 loading dose, then 250 mg/m2 weekly intravenously [I.V.]) plus bevacizumab 5 mg/kg and mFOLFOX6 chemotherapy every 2 weeks. The primary endpoint was toxicity. Results: The most common grade 3-4 events included diarrhea (14%), fatigue (14%), neuropathy (12%), venous thrombosis (9%), acneiform rash (8%), and desquamation (8%). A protocol-defined prohibitive adverse event occurred in 4 patients (6%), including 2 treatment-associated deaths. Thirty-seven patients (56%) discontinued therapy before disease progression because of either toxicity (n = 19; 29%) or patient withdrawal (n = 18; 27%). Twenty-eight of 37 patients (76%) who discontinued therapy before disease progression did so because of cetuximab-associated toxicity. Conclusion: Although the addition of cetuximab to bevacizumab plus mFOLFOX6 was not associated with excessive life-threatening toxicity, many patients discontinued therapy because of cetuximab-associated toxicity. Taken together with the results of recently reported phase III trials, cetuximab should not be used concurrently with bevacizumab and infusional 5-FU, leucovorin, and oxaliplatin chemotherapy for the treatment of mCRC.

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KW - Oxaliplatin

KW - Vascular endothelial growth factor

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