Celine Bourgier1, Anne Auperin2, Sofia Rivera3, Pierre Boisselier4, Benoit Petit5, Philippe Lang6, Nathalie Lassau7, Patrice Taourel8, Raphael Tetreau9, David Azria10, Jean Bourhis5, Eric Deutsch3, Marie-Catherine Vozenin5. 1. INSERM, U1194, IRCM, Université de Montpellier, Montpellier, France; Department of Radiation Oncology, ICM-Val d'Aurelle, Université de Montpellier, Montpellier, France. Electronic address: celine.bourgier@icm.unicancer.fr. 2. Biostatistics Department, Gustave Roussy Institute, Villejuif, France. 3. Department of Radiation Oncology, INSERM 1030, Université de Paris-Sud, Gustave Roussy Cancer Campus, Villejuif, France, Université de Paris-Saclay. 4. Department of Radiation Oncology, ICM-Val d'Aurelle, Université de Montpellier, Montpellier, France. 5. Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 6. Department of Radiation Oncology, Centre Hospitalier Universitaire, Université de Montpellier, Nîmes, France. 7. Imaging Department, Gustave Roussy Institute, IR4M, Université de Paris-Sud, Villejuif, France. 8. Radiology Department, Centre Hospitalier Universitaire, Lapeyronie, Université de Montpellier, Montpellier, France. 9. Radiology Department, ICM-Val d'Aurelle, Université de Montpellier, Montpellier, France. 10. INSERM, U1194, IRCM, Université de Montpellier, Montpellier, France; Department of Radiation Oncology, ICM-Val d'Aurelle, Université de Montpellier, Montpellier, France.
Abstract
PURPOSE: The "PRAVACUR" phase 2 trial (NCT01268202) assessed the efficacy of pravastatin as an antifibrotic agent in patients with established cutaneous and subcutaneous radiation-induced fibrosis (RIF) after head and neck squamous cell carcinoma (HNSCC) radiation therapy and/or radiochemotherapy. METHODS AND MATERIALS: The main inclusion criteria were: NSCC in remission, grade ≥2 cutaneous and subcutaneous neck RIF (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0), and no current treatment with statins or fibrates. Patients received pravastatin 40 mg/d for 12 months. The primary endpoint was reduction of RIF thickness by more than 30% at 12 months, as measured by cutaneous high-frequency ultrasonography. Secondary endpoints included RIF severity reduction, pravastatin tolerance, and quality of life. RESULTS: Sixty patients with grade 2 (n = 37), grade 3 (n = 22), or grade 4 (n = 1) RIF were enrolled from February 2011 to April 2016. The mean interval between RIF diagnosis and pravastatin initiation was 17.1 months. Pravastatin was stopped before 11 months of treatment in 18 patients (because of grade ≥2 adverse events related to pravastatin in 8 patients [13%]). In the 40 patients in whom pravastatin efficacy was assessed by high-frequency ultrasonography at baseline and at 12 months of treatment, a reduction of RIF thickness ≥30% was observed in 15 of 42 patients (35.7%; 95% confidence interval, 21.6%-52.0%). At the 12-month clinical evaluation, RIF severity was decreased in 50% of patients (n = 21; 95% confidence interval, 34.2%-65.8%), and the patients' self-perception, mood state, and social functioning were significantly improved. Pravastatin was well tolerated, with a very low occurrence of grade 3 toxicities (myalgia, n = 1) and grade 2 toxicities (myalgia/arthralgia or esophagitis, n = 3). CONCLUSIONS: This phase 2 prospective study supports the notion of radioinduced fibrosis reversibility. It showed that pravastatin (40 mg/d for 12 months) is an efficient antifibrotic agent in patients with grade ≥2 cutaneous and subcutaneous fibrosis after HNSCC radiation therapy.
PURPOSE: The "PRAVACUR" phase 2 trial (NCT01268202) assessed the efficacy of pravastatin as an antifibrotic agent in patients with established cutaneous and subcutaneous radiation-induced fibrosis (RIF) after head and neck squamous cell carcinoma (HNSCC) radiation therapy and/or radiochemotherapy. METHODS AND MATERIALS: The main inclusion criteria were: NSCC in remission, grade ≥2 cutaneous and subcutaneous neck RIF (National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0), and no current treatment with statins or fibrates. Patients received pravastatin 40 mg/d for 12 months. The primary endpoint was reduction of RIF thickness by more than 30% at 12 months, as measured by cutaneous high-frequency ultrasonography. Secondary endpoints included RIF severity reduction, pravastatin tolerance, and quality of life. RESULTS: Sixty patients with grade 2 (n = 37), grade 3 (n = 22), or grade 4 (n = 1) RIF were enrolled from February 2011 to April 2016. The mean interval between RIF diagnosis and pravastatin initiation was 17.1 months. Pravastatin was stopped before 11 months of treatment in 18 patients (because of grade ≥2 adverse events related to pravastatin in 8 patients [13%]). In the 40 patients in whom pravastatin efficacy was assessed by high-frequency ultrasonography at baseline and at 12 months of treatment, a reduction of RIF thickness ≥30% was observed in 15 of 42 patients (35.7%; 95% confidence interval, 21.6%-52.0%). At the 12-month clinical evaluation, RIF severity was decreased in 50% of patients (n = 21; 95% confidence interval, 34.2%-65.8%), and the patients' self-perception, mood state, and social functioning were significantly improved. Pravastatin was well tolerated, with a very low occurrence of grade 3 toxicities (myalgia, n = 1) and grade 2 toxicities (myalgia/arthralgia or esophagitis, n = 3). CONCLUSIONS: This phase 2 prospective study supports the notion of radioinduced fibrosis reversibility. It showed that pravastatin (40 mg/d for 12 months) is an efficient antifibrotic agent in patients with grade ≥2 cutaneous and subcutaneous fibrosis after HNSCC radiation therapy.
Authors: Carole Helissey; Sophie Cavallero; Clément Brossard; Marie Dusaud; Cyrus Chargari; Sabine François Journal: Cells Date: 2020-12-24 Impact factor: 6.600
Authors: Paul Ramia; Larry Bodgi; Dima Mahmoud; Mohammad A Mohammad; Bassem Youssef; Neil Kopek; Humaid Al-Shamsi; Mona Dagher; Ibrahim Abu-Gheida Journal: Clin Med Insights Oncol Date: 2022-01-30
Authors: Rémi Bourdais; Samir Achkar; Charles Honoré; Matthieu Faron; Andrea Cavalcanti; Guillaume Auzac; Carine Ngo; Leila Haddag-Miliani; Benjamin Verret; Sarah Dumont; Eric Deutsch; Axel Le Cesne; Olivier Mir; Cécile Le Péchoux; Antonin Levy Journal: Clin Transl Radiat Oncol Date: 2021-06-04