Prof. François Goldwasser

Presentation Roadmap/ Summary

Sarcopenia has emerged as an independent prognostic factor in oncology. It is also a clinical biomarker of vulnerability. Sarcopenia is favored both by reduced ingesta and/or inflammation. Reduced muscle mass is also responsible for reduced lean body mass and alterations of the pharmacokinetics of anticancer agents. Moreover, the calculated creatinine clearance, especially in sarcopenic overweight patients result in an overestimation of the renal function and overexposure to anticancer treatments. Patients with sarcopenia experience more acute limiting toxicity. Careful attention to muscle mass prior to initiate anticancer therapy is necessary to personalize therapies and optimize benefit/risk ratio.

Learning Objectives

At the conclusion of the presentation, the participant will be able to:

1. Know the prevalence and prognostic value of sarcopenia in oncology
2. Describe the relationship between muscle mass and the pharmacokinetics of anticancer agents
3. Describe the effects of anticancer agents on muscle mass

Key Takeaways/ Fast Facts

• Sarcopenia is an independent prognostic factor in oncology
• Sarcopenia is associated with overexposure to anticancer agents
• Sarcopenia is associated with increased vulnerability and increased limiting acute toxicity of anticancer agent          

Key references

1. Heidelberger V, Goldwasser F, Kramkimel N, Jouinot A, Huillard O, Boudou-Rouquette P, Chanal J, Arrondeau J, Franck N, Alexandre J, Blanchet B, Leroy K, Avril MF, Dupin N, Aractingi S. Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients. Invest New Drugs. 2017 Aug;35(4):436-441
2. Bigot F, Boudou-Rouquette P, Arrondeau J, Thomas-Schoemann A, Tlemsani C, Chapron J, Huillard O, Cessot A, Vidal M, Alexandre J, Blanchet B, Goldwasser F.Erlotinib pharmacokinetics: a critical parameter influencing acute toxicity in elderly patients over 75 years-old. Invest New Drugs. 2017 Apr;35(2):242-246.
3. Huillard O, Mir O, Peyromaure M, Tlemsani C, Giroux J, Boudou-Rouquette P, Ropert S, Delongchamps NB, Zerbib M, Goldwasser F. Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients. Br J Cancer. 2013 Mar 19;108(5):1034-41.
4. Mir O, Coriat R, Blanchet B, Durand JP, Boudou-Rouquette P, Michels J, Ropert S, Vidal M, Pol S, Chaussade S, Goldwasser F. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS One. 2012;7(5):e37563.
5. Cousin S, Hollebecque A, Koscielny S, Mir O, Varga A, Baracos VE, Soria JC, Antoun S. Low skeletal muscle is associated with toxicity in patients included in phase I trials. Invest New Drugs. 2014 Apr;32(2):382-7
6. Antoun S, Birdsell L, Sawyer MB, Venner P, Escudier B, Baracos VE. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol. 2010 Feb 20;28(6):1054-60
7. Antoun S, Baracos VE, Birdsell L, Escudier B, Sawyer MB. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol. 2010 Aug;21(8):1594-8.