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Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study)
BACKGROUND: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574110/ https://www.ncbi.nlm.nih.gov/pubmed/28841909 http://dx.doi.org/10.1186/s12885-017-3566-0 |
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author | Kim, Stefano Jary, Marine André, Thierry Vendrely, Véronique Buecher, Bruno François, Eric Bidard, François-Clément Dumont, Sarah Samalin, Emmanuelle Peiffert, Didier Pernot, Simon Baba-Hamed, Nabil El Hajbi, Farid Bouché, Olivier Desrame, Jérôme Parzy, Aurélie Zoubir, Mustapha Louvet, Christophe Bachet, Jean-Baptiste Nguyen, Thierry Abdelghani, Meher Ben Smith, Denis De La Fouchardière, Christelle Aparicio, Thomas Bennouna, Jaafar Gornet, Jean-Marc Jacquin, Marion Bonnetain, Franck Borg, Christophe |
author_facet | Kim, Stefano Jary, Marine André, Thierry Vendrely, Véronique Buecher, Bruno François, Eric Bidard, François-Clément Dumont, Sarah Samalin, Emmanuelle Peiffert, Didier Pernot, Simon Baba-Hamed, Nabil El Hajbi, Farid Bouché, Olivier Desrame, Jérôme Parzy, Aurélie Zoubir, Mustapha Louvet, Christophe Bachet, Jean-Baptiste Nguyen, Thierry Abdelghani, Meher Ben Smith, Denis De La Fouchardière, Christelle Aparicio, Thomas Bennouna, Jaafar Gornet, Jean-Marc Jacquin, Marion Bonnetain, Franck Borg, Christophe |
author_sort | Kim, Stefano |
collection | PubMed |
description | BACKGROUND: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients. METHODS: This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon’s optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy. DISCUSSION: Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA. TRIAL REGISTRATION: NCT02402842, EudraCT: 2014–001789-81. |
format | Online Article Text |
id | pubmed-5574110 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55741102017-08-30 Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) Kim, Stefano Jary, Marine André, Thierry Vendrely, Véronique Buecher, Bruno François, Eric Bidard, François-Clément Dumont, Sarah Samalin, Emmanuelle Peiffert, Didier Pernot, Simon Baba-Hamed, Nabil El Hajbi, Farid Bouché, Olivier Desrame, Jérôme Parzy, Aurélie Zoubir, Mustapha Louvet, Christophe Bachet, Jean-Baptiste Nguyen, Thierry Abdelghani, Meher Ben Smith, Denis De La Fouchardière, Christelle Aparicio, Thomas Bennouna, Jaafar Gornet, Jean-Marc Jacquin, Marion Bonnetain, Franck Borg, Christophe BMC Cancer Study Protocol BACKGROUND: The squamous cell carcinoma of the anus (SCCA) is a rare disease, but its incidence is markedly increasing. About 15% of patients are diagnosed at metastatic stage, and more than 20% with a localized disease treated by chemoradiotherapy (CRT) will recur. In advanced SCCA, cisplatin and 5-fluorouracil (CF) combination is the standard option but complete response is a rare event and the prognosis remains poor with most disease progression occurring within the first 12 months. We have previously published the potential role of the addition of docetaxel (D). Among 8 consecutive patients with advanced recurrent SCCA after CRT, the DCF regimen induced a complete response in 4 patients, including 3 pathological complete responses. Then, the Epitopes-HPV02 study was designed to confirm the interest of DCF regimen in SCCA patients. METHODS: This multicentre phase II trial assesses the DCF regimen in advanced SCCA patients. Main eligibility criteria are: histologically proven SCCA, unresectable locally advanced recurrent or metastatic disease, Eastern Cooperative Oncology Group-performance status (ECOG-PS) <2, and being eligible for DCF. Patients receive either 6 cycles of standard DCF or 8 cycles of modified DCF depending on age (> vs. ≤ 75 years-old) and ECOG-PS (0 vs. 1). The trial was set up based on a Simon’s optimal two-stage design for phase II trials, allowing an early futility interim analysis. The primary endpoint is the observed progression-free survival (PFS) rate at 12 months from the first DCF cycle. A PFS rate below 10% is considered uninteresting, while a PFS rate above 25% is expected. With a unilateral alpha error of 5% and a statistical power of 90%, 66 evaluable patients should be included. Main secondary endpoints are overall survival, PFS, response rate, safety, health-related quality of life, and the correlation of biomarkers with treatment efficacy. DISCUSSION: Since the recommended CF regimen is based in a small retrospective analysis and generates a low rate of complete responses, the Epitopes-HPV02 study will establish a new standard in case of a positive result. Associated biomarker studies will contribute to understand the underlying mechanism of resistance and the role of immunity in SCCA. TRIAL REGISTRATION: NCT02402842, EudraCT: 2014–001789-81. BioMed Central 2017-08-25 /pmc/articles/PMC5574110/ /pubmed/28841909 http://dx.doi.org/10.1186/s12885-017-3566-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Study Protocol Kim, Stefano Jary, Marine André, Thierry Vendrely, Véronique Buecher, Bruno François, Eric Bidard, François-Clément Dumont, Sarah Samalin, Emmanuelle Peiffert, Didier Pernot, Simon Baba-Hamed, Nabil El Hajbi, Farid Bouché, Olivier Desrame, Jérôme Parzy, Aurélie Zoubir, Mustapha Louvet, Christophe Bachet, Jean-Baptiste Nguyen, Thierry Abdelghani, Meher Ben Smith, Denis De La Fouchardière, Christelle Aparicio, Thomas Bennouna, Jaafar Gornet, Jean-Marc Jacquin, Marion Bonnetain, Franck Borg, Christophe Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) |
title | Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) |
title_full | Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) |
title_fullStr | Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) |
title_full_unstemmed | Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) |
title_short | Docetaxel, Cisplatin, and 5-fluorouracil (DCF) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase II study of French interdisciplinary GERCOR and FFCD groups (Epitopes-HPV02 study) |
title_sort | docetaxel, cisplatin, and 5-fluorouracil (dcf) chemotherapy in the treatment of metastatic or unresectable locally recurrent anal squamous cell carcinoma: a phase ii study of french interdisciplinary gercor and ffcd groups (epitopes-hpv02 study) |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574110/ https://www.ncbi.nlm.nih.gov/pubmed/28841909 http://dx.doi.org/10.1186/s12885-017-3566-0 |
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