1. Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16 phase II trial†
- Author
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L. Miglianico, D. Azria, E. Paris, Patrick Ezra, C. Lemanski, Beata Juzyna, Katty Malekzadeh, Anne Delarochefordiere, Emmanuel Rio, J.P. Pignon, Eric Deutsch, Isabelle Martel-Lafay, T. Conroy, Yves Becouarn, David Malka, Antonin Levy, Institut Gustave Roussy (IGR), CRLCC Val d'Aurelle - Paul Lamarque, Institut Curie [Paris], Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre Hospitalier Privé Saint-Grégoire, Institut Bergonié [Bordeaux], UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut Curie, Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), and Institut Bergonié - CRLCC Bordeaux
- Subjects
Male ,MESH: Radiotherapy ,Phases of clinical research ,Gastroenterology ,chemoradiotherapy ,MESH: Anus Neoplasms ,0302 clinical medicine ,MESH: Cetuximab ,cetuximab ,Medicine ,MESH: Chemoradiotherapy ,MESH: Aged ,0303 health sciences ,education.field_of_study ,MESH: Middle Aged ,Cetuximab ,Hematology ,Middle Aged ,phase II ,Anus Neoplasms ,targeted therapy ,MESH: Drug-Related Side Effects and Adverse Reactions ,3. Good health ,Oncology ,Fluorouracil ,030220 oncology & carcinogenesis ,Female ,MESH: Neoplasm Recurrence, Local ,medicine.drug ,Adult ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,anal cancer ,Population ,Antibodies, Monoclonal, Humanized ,Loading dose ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Anal cancer ,Humans ,education ,Adverse effect ,030304 developmental biology ,Aged ,MESH: Humans ,Radiotherapy ,business.industry ,toxicity ,MESH: Adult ,medicine.disease ,MESH: Male ,Surgery ,MESH: Cisplatin ,MESH: Antibodies, Monoclonal, Humanized ,MESH: Disease-Free Survival ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Cisplatin ,Neoplasm Recurrence, Local ,business ,MESH: Fluorouracil ,MESH: Female ,Chemoradiotherapy - Abstract
Background The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). Patients and methods Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m2 with a loading dose of 400 mg/m2 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. Results The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18–27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%–86%), 62% (95% CI: 36%–82%), and 92% (95% CI: 67%–99%), respectively. Conclusion CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. Eudra CT No 2007-007029-38.
- Published
- 2013
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