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).


Journal

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192

Informations de publication

Date de publication:
11 2019
Historique:
received: 20 12 2018
revised: 14 05 2019
accepted: 15 05 2019
pubmed: 12 6 2019
medline: 29 4 2020
entrez: 12 6 2019
Statut: ppublish

Résumé

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. 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. 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 The MTD is 5FU at 400 mg/m

Sections du résumé

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
CONCLUSIONS
The MTD is 5FU at 400 mg/m

Identifiants

pubmed: 31185328
pii: S0167-8140(19)32919-6
doi: 10.1016/j.radonc.2019.05.018
pii:
doi:

Substances chimiques

Mitomycin 50SG953SK6
Panitumumab 6A901E312A
ErbB Receptors EC 2.7.10.1
Fluorouracil U3P01618RT

Types de publication

Clinical Trial, Phase I Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

84-89

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Véronique Vendrely (V)

CHU de Bordeaux, Pessac, France. Electronic address: veronique.vendrely@chu-bordeaux.fr.

Claire Lemanski (C)

Institut Regional du Cancer Montpellier, France.

Khemara Gnep (K)

Centre Eugene Marquis, Rennes, France.

Emilie Barbier (E)

Biostatistics, FFCD, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France.

Farid El Hajbi (FE)

Centre Oscar Lambret, Lille, France.

Gerard Lledo (G)

Hopital prive Jean Mermoz, Lyon, France.

Laëtitia Dahan (L)

CHU La Timone, Marseille, France.

Eric Terrebonne (E)

CHU de Bordeaux, Pessac, France.

Sylvain Manfredi (S)

Centre Eugene Marquis, Rennes, France.

Xavier Mirabel (X)

Centre Oscar Lambret, Lille, France.

Vincent Mammar (V)

Hopital prive Jean Mermoz, Lyon, France.

Didier Cowen (D)

CHU La Timone, Marseille, France.

Come Lepage (C)

EPICAD INSERM LNC-UMR 1231 University of Burgundy and Franche Comté, Dijon, France.

Thomas Aparicio (T)

CHU APHP - Saint-Louis, Paris, France.

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Classifications MeSH