System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print

PubMed: 41865627 DOI: 10.1016/j.biopha.2026.119242

Analysis of the relationship between body composition and the pharmacokinetics of panitumumab in the treatment of localized squamous cell carcinoma of the anus - An ancillary study of the FFCD0904 phase I and II trial.

Biomed Pharmacother 198:119242

Authors: Sarah Lobet, David Ternant, Come Lepage, Karine Le Malicot, Nicolas Azzopardi, Adeline Dolly, Franck Nguyen, Lucie Lagogué, Louis Bazire, Claire Lemanski, Jérôme Martin-Babau, Astrid Lièvre, Christelle De la Fouchardière, Meher Ben Abdelghani, Gilles Paintaud, Thomas Aparicio, Véronique Vendrely, Thierry Lecomte

Affiliations

  • INSERM UMR 1069, N2COx "Niche, Nutrition, Cancer and Oxidative Metabolism", Université de Tours, Tours, France.
  • Service de Pharmacologie Médicale, CHU de Tours, Tours, France; Plateforme Recherche, Centre Pilote de suivi Biologique des traitements par Anticorps, CHU de Tours, Tours, France.
  • Fédération Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, Faculté de Médecine, University of Burgundy Europe, Dijon, France; Hépato-gastroenterology & Digestive Oncology, CHU Dijon Bourgogne, University of Burgundy Europe, Dijon, France.
  • Fédération Francophone de Cancérologie Digestive (FFCD), EPICAD INSERM LNC-UMR 1231, Faculté de Médecine, University of Burgundy Europe, Dijon, France.
  • INRAE, CNRS, Université de Tours, PRC, Nouzilly, France.
  • Service d'oncologie radiothérapie, Institut Curie, Saint Cloud, Paris, France.
  • Service d'oncologie radiothérapie, Institut Du Cancer De Montpellier, Montpellier, France.
  • Service d'oncologie médicale, CARIO Hôpital Privé des Côtes d'Armor, Plerin sur Mer, France.
  • Service des maladies de l'appareil digestif, CHU de Rennes, INSERM U1242, Université de Rennes, Rennes, France.
  • Service d'oncologie médicale, Institut Paoli-Calmettes, Marseille, France.
  • Service d'oncologie médicale, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg, France.
  • Service de Pharmacologie Médicale, CHU de Tours, Tours, France; INSERM UMR 1327 Ischemia, Université de Tours, Tours, France.
  • Service d'Hépato-gastroentérologie et de cancérologie digestive, Hôpital Saint-Louis, AP-HP, Paris, France.
  • Service de radiothérapie, CHU de Bordeaux, Bordeaux, France.
  • INSERM UMR 1069, N2COx "Niche, Nutrition, Cancer and Oxidative Metabolism", Université de Tours, Tours, France; Service d'Hépato-gastroentérologie et de cancérologie digestive, CHU de Tours, Tours, France.

Abstract

BACKGROUND AND AIMS

Cancer-related cachexia alters body composition (BC) and organ function, potentially affecting drug pharmacokinetics (PK).This ancillary study of the FFCD0904 phase I/II trial, which evaluated panitumumab -based radiochemotherapy in localized squamous cell carcinoma (SCC) of the anus, explored association between panitumumab PK, BC and its effects.

METHODS

Panitumumab PK parameters were estimated using a population PK approach. Pre-treatment CT scans at L3 were used to assess BC. Skin toxicity and efficacy data (tumor response, survival) were analyzed in relation to BC and PK parameters.

RESULTS

Among 54 patients, 35 had panitumumab PK measurements, 42 had baseline CT scans, and 36 had skin toxicity data. In 25 patients with complete BC and PK data, AUC 0-14 and clearance (CL)tended to be positively correlated with body weight (BW, p = 0.0025 and 0.031), fat mass (FM, p = 0.027 and 0.033), and fat-free mass (FFM, p = 0.059 and 0.049),).Non-sarcopenic patients tended to show higher AUC 0-14 than sarcopenic patients (p = 0.0016). Lower albumin appeared to be associated with reduced clearance (p = 0.015). Despite these PK associations, neither BC nor panitumumab exposure seems correlated with tumor response, survival, or early skin toxicity.

CONCLUSION

This exploratory analysis suggests that BW and BC may influence panitumumab PK, with patients who had lower BW, FM and FFM might have reduced exposure and clearance. Interpretation should be cautious due to the small sample size, confounding effect between BC and BW and potential disease-related effects. Larger studies with longitudinal BC and PK assessments are needed to clarify these relationships and guide dosing strategies.

MeSH

Skin, Cells, Carcinoma, Squamous Cell, Neoplasms, Body Composition, Drug Therapy, Panitumumab, Research, Therapeutics, Pharmacokinetics