LETTER TO THE EDITOR Locally advanced anal canal carcinoma: is the addition of cetuximab the answer? Francesca De Felice 1 & Daniela Musio 1 & Vincenzo Tombolini 1,2 Accepted: 8 May 2015 # Springer-Verlag Berlin Heidelberg 2015 Dear Editor: Carcinoma of the anal canal is a rare disease accounting 7.270 estimated new cancer cases in 2015, with increasing incidence over the last decades [1]. The efficacy of radiation therapy combined with chemotherapy (CRT) as treatment for anal canal carcinoma has been convincingly proven. Prior to the 1970s, treatment consisted of radical surgery with abdominoperineal resection. Relying on Nigro’s intuitions, several randomized clinical trials tested the use of radiothera- py combined with chemotherapy and demonstrated a signifi- cantly higher colostomy-free survival with the addition of mitomycin-C (MMC) to infusional 5-fluorouracil (5-FU) and radiation. This method was first described by Nigro in 1974. Since then, no other effective treatment was devel- oped—two randomized trials tested whether cisplatin (CDDP) could be used instead of MMC to improve local and distant control, but results failed in their objective. Despite a better quality of life, this treatment approach guarantees different clinical outcome, depending on stage disease at di- agnosis [2, 3]. Briefly the 5-year survival rates are >90 % for T1, >80 % for T2, 45–55 % for T3–4 and 65–75 % overall. Due to the high incidence of local failure, patients with locally advanced disease (tumour staged T3–4 and/or lymph-nodes pos- itive) should be considered candidates for clinical trials. We be- lieve that, in this patients group, the therapeutic standard ap- proach — RT with concomitant 5-FU and MMC — should be optimized to include biologic-based treatment. Squamous cell carcinoma is known to be sensitive to radiation. Moreover, there is evidence that molecular target therapy, given simulta- neously with radiation, tends to potentiate its effect. It would seem logical to use target therapy in combination with con- comitant radio-chemotherapy. At present, surgery is used main- ly as salvage treatment; the association of RT, 5-FU and MMC is the recommended management approach. In parallel, there is an emerging appreciation for radiosensitizing properties of cetuximab, an IgG1 chimeric monoclonal antibody, against the epidermal growth factor receptor (EGFR). EGFR is a trans- membrane protein that is frequently overexpressed in squa- mous cell cancers, comprising anal canal carcinoma. Both in vitro and in vivo studies demonstrated that cetuximab acts as a strong radiosensitizer, reducing cellular proliferation. The cetuximab optimum biological dose (OBD) was defined to be doses between 200 and 400 mg/m 2 . Nowadays, it has been recognized as a first-line treatment option in addition to radio- therapy for locoregionally advanced squamous cell carcinoma of the head and neck. Olivatto et al. [4] designed a phase I study to test whether cetuximab could be integrated with radio- chemotherapy cisplatin-based therapy in locally advanced anal canal carcinoma. Due to the high toxicity rate, this combination was not recommended. But this study could be criticized be- cause cisplatin-based therapy schedule does not represent the optimum association irradiation-drugs agent in anal canal car- cinoma. Adding cetuximab to standard treatment could be a potential strategy for improving outcomes in locally advanced anal canal carcinoma. The theoretic effectiveness of cetuximab administration in association with standard CRT treatment, in locally advanced anal canal carcinomas, should be demonstrat- ed and confirmed in randomized trials. Sphincter-conserving approaches are assumed to be the gold standard treatment for locally advanced anal carcinoma, while abdominoperineal re- section with colostomy is performed when patients require a salvage surgery. Radiotherapy combined with chemotherapy * Francesca De Felice fradefelice@hotmail.it 1 Department of Radiotherapy, Policlinico Umberto I BSapienza^, University of Rome, Viale Regina Elena 326, 00161 Rome, Italy 2 Spencer-Lorillard Foundation, Viale Regina Elena 262, Rome, Italy Int J Colorectal Dis DOI 10.1007/s00384-015-2243-5