Metastatic Colorectal Cancer Treated with FOLFOX + Cetuximab in Long Term Use Protocol. Complete Responses and Acceptable Tolerability Profie. Case Series


  • Besteiro A.V.M.
  • Puty T.C.
  • Dias M.S.
  • Semblano A.A.P
  • Carvalho L.E.W.



colorectal cancer, metastasis, complete radiological response, toxicity management, overall survival


Cetuximab, an anti-EGFR monoclonal antibody, has shown benefits when combined with the standard chemotherapy protocol for treating metastatic colorectal cancer (mCRC) in patients with wild-type Kras, either as the first-line or subsequent-line treatment. The most frequent profiles of toxicity are hematologic (8% grade 3 and 5% grade 4), dermatologic (24% grade 3 and 2% grade 4), acneiform exanthem (17% grade 3 and 0% grade 4) and diarrhea (10% grade 3 and 1% grade 4), which are critical for the maintenance of therapeutic regimens until disease progression. Thus, this study aims to report the cases of two patients with mCRC undergoing FOLFOX protocol associated with Cetuximab as first-line for metastatic disease. Both patients were male, older and with good clinical performance (ECOG 0,1). The subjects were followed for five years. Radiological complete responses were observed, encouraging continuity of care in Long Term Use (LTU). Clinical and radiological outcomes were unequivocally represented by complete responses, associated with acceptable and manageable tolerability profiles, culminating in overall survival (OS) over 60 months (5 years) from diagnosis. Thus, the data reported in this case series corroborate the data from current studies demonstrating benefits of anti-EGFR therapy in selected populations of patients with wild-type Kras, as first shown in OPUS study and more recently in the CALGB/SWOG 80405 study, emphasizing that treatment of mCRC with new oncogenetically guided approaches can significantly increase OS and tumor regression rates at LTU protocols.


Rebecca Siegel MPH, Jiemin Ma PhD, Zhaohui Zou MS and Ahmedin Jemal DVM, PhD. Global cancer statistics. CA: A Cancer Journal for Clinicians, Volume 64, Issue 1, pages 9–29, January/February 2014.

Strategies to overcome resistance to epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer. World J Gastroenterol. 2014; Aug 7;20(29):9862-9871.

Tournigand C, André T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A.FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004 Jan 15;22(2):229-37. Epub 2003 Dec 2.

Goldberg, R, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, et al. Modified FOLFOX 6 widely used but not published. J Clin Oncol 2004;22:23-30.

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. JClinOncol2009; 27: 663-671 [PMID: 19114683 DOI: 10.1200/ jco.2008.20.8397].

Heinemann, V, von Weikersthal, LF, Decker, T et al. FOLFIRI plus cetuximabe versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014; 15: 1065–107.

Venook, AP, Niedzwiecki, D, Lenz, H-J et al. Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximabe (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). Proc Am Soc Clin Oncol. 2014; 32 (abstr LBA3.).

Bokemeyer C, Bondarenko I, Hartmann JT, et al: KRAS status and efficacy of first-line treatment of patients with metastatic colorectal (metastatic CRC) with FOLFOX with or without cetuximab: The OPUS experience. J Clin Oncol 26:178s, 2008 (suppl; abstr 4000).

Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8.

De Roock W, Piessevaux H, De Schutter J, et al: KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19:508-515, 2008.

Allegra CJ, Jessup JM, Somerfield MR, et al, “American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy, †J Clin Oncol, 2009, 27(12):2091-6.

Zhong-chuan Lv & Jin-yao Ning & Hong-bing Chen. Efficacy and toxicity of adding cetuximab to chemotherapy in the treatment of metastatic colorectal cancer: a meta-analysis from 12 randomized controlled trials. Tumor Biol. (2014) 35:11741–11750.

F. Petrelli, K. Borgonovo, S. Barni. The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials. Targeted Oncology. September 2013, Volume 8, Issue 3, pp 173-18.

Lenz H, Niedzwiecki D, Innocenti F, Blanke C, Mahony M, O’Neil B, Shaw J, Polite B, Hochster H, A tkins J, Goldberg R, Mayer R, Schilsky R, Bertagnolli M, Venook A. CALGB/SWOG 80405: PHASE III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (BV) or cetuximab (CET) for patients (pts) with expanded ras analyses untreated metastatic adenocarcinoma of the colon or rectum. ESMO2014; abstr 5010.

Susan Mayor PhD. Medical News Today. Early Tumor Shrinkage With Cetuximab Correlates With Prolonged Survival In Metastatic Colorectal Cancer. 11 June 2012 Disponível em:<> Acesso em: 17 abril 2015.