1. Anti-epidermal growth factor receptor therapy in combination with chemoradiotherapy for the treatment of locally advanced anal canal carcinoma: Results of a phase I dose-escalation study with panitumumab (FFCD 0904).
- Author
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Vendrely V, Lemanski C, Gnep K, Barbier E, Hajbi FE, Lledo G, Dahan L, Terrebonne E, Manfredi S, Mirabel X, Mammar V, Cowen D, Lepage C, and Aparicio T
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Female, Fluorouracil administration & dosage, Humans, Male, Middle Aged, Mitomycin administration & dosage, Prospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Anus Neoplasms therapy, Chemoradiotherapy, ErbB Receptors antagonists & inhibitors, Panitumumab administration & dosage
- Abstract
Background and Purpose: Standard treatment of epidermoid anal cancer is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase I study aims to evaluate the addition of panitumumab (Pmab) to CRT and to determine the maximum tolerated dose (MTD) of Pmab and 5-FU in combination with CRT., Materials and Methods: Immunocompetent patients with locally advanced tumour without metastases (Stage T2, T3 or T4, whatever N stage; Stage N1-N3 whatever T stage) followed two RT periods (45 Gy in 5 weeks and 20 Gy in 2 weeks, separated by a 2-week break) with concomitant CT sessions of 5FU/MMC at RT weeks 1, 5 and 8. Pmab was administered on RT weeks 1, 3, 5, 8 and 10 according to a predefined dose escalation schedule., Results: Ten patients were enroled. One was excluded due to unmet dose constraints respect. Three patients received dose level (DL) 0 (Pmab 3 mg/kg + 5FU 600 mg/m
2 /day) and six received DL-1 (Pmab 3 mg/kg + 5FU 400 mg/m2 /day). Dose-limiting toxicities occurred in all patients at DL 0 and 2 at DL-1. Most common grade 3-4 toxicities observed at DL 0 were haematologic (100%), dermatitis (67%), and anaemia (67%). No death occurred. Four months after ending CRT, five and two patients had a local complete response and a partial response, respectively. One patient had a colostomy with abdomino-perineal amputation due to a tumour recurrence., Conclusions: The MTD is 5FU at 400 mg/m2 /day, MMC at 10 mg/m2 and Pmab at 3 mg/kg. The effect of the MTD on tumour response is evaluated in the phase 2 study., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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