Phase I study of cetuximab (CET) in combination with 5-fluorouracil (5-FU) , cisplatin (CP) , and radiotherapy (RT) in patients with locally advanced squamous cell anal carcinoma (LAAC)
Olivatto, L.O.; Meton, F.; Bezerra, M.; Cardoso, A.; Araujo, C.M.; Castro, L.; Moura, R.; Pereira, B.V.; Ferreira, C.G.
Journal of Clinical Oncology 26(15_Suppl): 4609-4609
2016
ISSN/ISBN: 0732-183X PMID: 27948501 Accession: 058542233
NlmCategory="UNASSIGNED">4609 Background: Although chemoradiation (CRT) is a curable approach to anal carcinoma, 50% of the patients (pts) with LAAC eventually recur. Novel therapeutic strategies are needed for this population. CET is a monoclonal antibody directed against the EGFR, which is strongly expressed in anal carcinoma. Synergy of CET with RT resulted in improved survival (vs. RT alone) in head and neck cancer. This trial evaluates the feasibility and tolerability of CET/5-FU/CP combined to RT in LAAC, with maximal tolerated dose as primary endpoint. Pts with LAAC (T3-T4 and/or N+ disease per proctoscopy and MRI) received RT 45 Gy/1.8Gy day/5wks plus boost 10 Gy (2 Gy/day) to a total dose of 55 Gy in combination with CET (400mg/m2 on d1, then 7 weekly doses of 250 mg/m2). Combination chemotherapy with 96-hour infusion of escalating-dose of 5-FU and 2-hour infusion of escalating-dose CP, both on days 1 and 29 according to the following design: starting dose level (0) 800 and 60 mg/m2/day, dose level (-1) 600 and 50 mg/m2/day, dose level (+1) 800 and 80 mg/m2/day and dose level (+2) 1000 and 80 mg/m2/day. A standard 3+3 design was used. Grade 4 hematologic toxicities, grade 4 radiation dermatitis, uncontrolled diarrhea or cumulative density of dose > 70% for all treatments were included as dose-limiting toxicities (DLTs). 10 patients (2 m/8f) stages T3N0:2, T2N2:2, T3N2:1, T2N3:2, T3N3:2, T4N0:1 have been enrolled. All pts completed full dose RT within 68 days (median, [50-98]). As on dose level 0 one DLT (grade 4 neutropenic fever) occurred, it was extended to 7 pts. No further DLT was observed on levels +1. Toxicities are displayed in the table . To date, out of 09 pts evaluable for pathological response, 07 achieved pCR (78%). CRT with 5-FU/CP plus CET seems feasible without unexpected toxicities with provocative preliminary efficacy in LAAC. The recommended doses for phase II will be available by April 2008. Study supported by Merck KGaA. [Table: see text] No significant financial relationships to disclose.