Definitive chemoradiotherapy plus cetuximab for cancer in the oesophagus or gastro-oesophageal junction.


Journal

Cancer treatment and research communications
ISSN: 2468-2942
Titre abrégé: Cancer Treat Res Commun
Pays: England
ID NLM: 101694651

Informations de publication

Date de publication:
2020
Historique:
received: 18 03 2019
revised: 20 06 2020
accepted: 22 06 2020
pubmed: 4 7 2020
medline: 4 5 2021
entrez: 4 7 2020
Statut: ppublish

Résumé

Chemoradiotherapy is standard treatment for localized oesophageal cancer unsuitable for surgery. We aimed to evaluate the efficacy of cetuximab in combination with chemoradiotherapy. This non-randomised multicentre phase II trial recruited patients aged 18-75 with WHO performance status 0-2 having squamous cell carcinoma or adenocarcinoma in the oesophagus or gastro-oesophageal junction, T2-4, N0-3, M0 not suitable for surgery. Chemotherapy was three 21-day cycles of fluorouracil 750 mg/m2 D1-5 and oxaliplatin D1 (cycle 1:130mg/m 2, cycle 2-3:85 mg/m 2). Radiotherapy was 50Gy in 2Gy/fraction, 5 days a week, concurrent with cycle 2 and 3 and weekly cetuximab. The primary objective was loco-regional control at one year. 52 patients were included. 51 were eligible for toxicity and survival analysis and 46 for recurrence analysis. Full radiotherapy dose was delivered to 80%, 75% received all three cycles of chemotherapy and 75% received four or more doses of cetuximab. The most common related grade III-IV adverse events were gastro-intestinal(16), hypersensitivity(6) and infection(5). There were two drug-related deaths. Within six months from the end of treatment, six patients died from complications from fistulas. The loco-regional control rate at one year was 47.3%(95%CI 30.9%-62.1%). Overall survival at three years was 29.1%(95% CI 17.4-41.9%). Oxaliplatin and fluorouracil given concurrent with radiotherapy and cetuximab had an acceptable safety profile and showed a clinical response in patients with locoregionally advanced oesophageal cancer unsuitable for surgery. However, the primary end-point was not met, and the addition of cetuximab to definitive chemoradiotherapy cannot be recommended.

Sections du résumé

BACKGROUND
Chemoradiotherapy is standard treatment for localized oesophageal cancer unsuitable for surgery. We aimed to evaluate the efficacy of cetuximab in combination with chemoradiotherapy.
METHODS
This non-randomised multicentre phase II trial recruited patients aged 18-75 with WHO performance status 0-2 having squamous cell carcinoma or adenocarcinoma in the oesophagus or gastro-oesophageal junction, T2-4, N0-3, M0 not suitable for surgery. Chemotherapy was three 21-day cycles of fluorouracil 750 mg/m2 D1-5 and oxaliplatin D1 (cycle 1:130mg/m 2, cycle 2-3:85 mg/m 2). Radiotherapy was 50Gy in 2Gy/fraction, 5 days a week, concurrent with cycle 2 and 3 and weekly cetuximab. The primary objective was loco-regional control at one year.
RESULTS
52 patients were included. 51 were eligible for toxicity and survival analysis and 46 for recurrence analysis. Full radiotherapy dose was delivered to 80%, 75% received all three cycles of chemotherapy and 75% received four or more doses of cetuximab. The most common related grade III-IV adverse events were gastro-intestinal(16), hypersensitivity(6) and infection(5). There were two drug-related deaths. Within six months from the end of treatment, six patients died from complications from fistulas. The loco-regional control rate at one year was 47.3%(95%CI 30.9%-62.1%). Overall survival at three years was 29.1%(95% CI 17.4-41.9%).
CONCLUSIONS
Oxaliplatin and fluorouracil given concurrent with radiotherapy and cetuximab had an acceptable safety profile and showed a clinical response in patients with locoregionally advanced oesophageal cancer unsuitable for surgery. However, the primary end-point was not met, and the addition of cetuximab to definitive chemoradiotherapy cannot be recommended.

Identifiants

pubmed: 32619832
pii: S2468-2942(20)30024-1
doi: 10.1016/j.ctarc.2020.100187
pii:
doi:

Substances chimiques

Cetuximab PQX0D8J21J

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

100187

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no conflicts of interest.

Auteurs

Gabriella Alexandersson von Döbeln (GA)

Theme Cancer, Karolinska University Hospital, Stockholm, Sweden. Electronic address: gabriella.alexandersson-vondobeln@sll.se.

Gunnar Wagenius (G)

Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.

Eva Holtved (E)

Department of Oncology, Odense University Hospital, Odense, Denmark.

Anne-Birgitte Jacobsen (AB)

Department of Oncology, Oslo University hospital, Oslo, Norway.

Magnus Nilsson (M)

Department of Clinical Sciences Intervention and Technology Karolinska Institutet Division of Upper Abdominal Cancer, Karolinska University Hospital, Stockholm, Sweden.

Jingru Yu (J)

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Lene Baeksgaard (L)

Department of Oncology, Rigshospitalet, Copenhagen, Denmark.

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Classifications MeSH