Neoadjuvant radiotherapy combined with fluorouracil-cisplatin plus cetuximab in operable, locally advanced esophageal carcinoma: Results of a phase I-II trial (FFCD-0505/PRODIGE-3).

Autor:	de Rauglaudre B; Department of Digestive Oncology, Hôpital la Timone, Marseille, France., Piessen G; Department of Digestive Surgery, University Hospital Huriez, Lille, France., Jary M; Department of Digestive Surgery, University Hospital Estaing, Clermont-Ferrand, France., Le Malicot K; Fédération Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche-Comté, Dijon, France., Adenis A; Department of Medical Oncology, Centre Oscar Lambret, Lille, France., Mazard T; Department of Medical Oncology, ICM Val d'Aurelle, Montpellier, France., D'Journo XB; Department of Thoracic Surgery, Aix-Marseille University, Hôpital Nord, Marseille, France., Petorin C; Department of Digestive Surgery, University Hospital Estaing, Clermont-Ferrand, France., Buffet-Miny J; Department of Radiotherapy, University Hospital Jean Minjoz, Besançon, France., Aparicio T; Department of Digestive Oncology, Hôpital Saint-Louis, Paris, France., Guimbaud R; Department of Medical Oncology, CHU de Toulouse, Toulouse, France., Vendrely V; Department of Radiotherapy, Hôpital Saint-André, Bordeaux, France., Lepage C; Fédération Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche-Comté, Dijon, France.; Department of Digestive Oncology, Hôpital François Mitterrand, Dijon, France., Dahan L; Department of Digestive Oncology, Hôpital la Timone, Marseille, France.
Jazyk:	angličtina
Zdroj:	Clinical and translational radiation oncology [Clin Transl Radiat Oncol] 2024 Jun 09; Vol. 47, pp. 100804. Date of Electronic Publication: 2024 Jun 09 (Print Publication: 2024).
DOI:	10.1016/j.ctro.2024.100804
Abstrakt:	Background: Radiotherapy combined with fluorouracil (5FU) and cisplatin for locally advanced esophageal cancer is associated with a 20-25% pathologic complete response (pCR) rate. Cetuximab increases the efficacy of radiotherapy in patients with head and neck carcinomas. The aim of this phase I/II trial was to determine the optimal doses and the pCR rate with chemoradiotherapy (C-RT) plus cetuximab. Methods: A 45-Gy radiotherapy regimen was delivered over 5 weeks. The phase I study determined the dose-limiting toxicity and the maximum tolerated dose of 5FU-cisplatin plus cetuximab. The phase II trial aimed to exhibit a pCR rate > 20 % (25 % expected), requiring 33 patients (6 from phase I part plus 27 in phase II part). pCR was defined as ypT0Nx. Results: The phase I study established the following recommended doses: weekly cetuximab (400 mg/m 2 one week before, and 250 mg/m 2 during radiotherapy); 5FU (500 mg/m 2 /day, d1-d4) plus cisplatin (40 mg/m 2 , d1) during week 1 and 5. In the phase II part, 32 patients received C-RT before surgery, 31 patients underwent surgery, and resection was achieved in 27 patients. A pCR was achieved in five patients (18.5 %) out of 27. After a median follow-up of 19 months, the median progression-free survival was 13.7 months, and the median overall survival was not reached. Conclusions: Adding cetuximab to preoperative C-RT was toxic and did not achieve a pCR > 20 % as required. The recommended doses, determined during the phase I part, could explain these disappointing results due to a reduction in chemotherapy dose-intensity. Trial Registration: This trial was registered with EudraCT number 2006-004770-27. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TA declares Conference for Pfizer, Roche, Sanofi, Léo Pharma, Amgen, BMS, Servier, Shire, Ipsen ; Board for Pierre Fabre Ipsen, HalioDX, BMS ; Travels and congress for Ipsen, Novartis, Roche, Hospira : Research grant from Novartis. RG declares travels grants and congress registration from Merck. (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)
Databáze:	MEDLINE
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