Chemotherapy dosing is challenging due to a narrow therapeutic index and significant toxicity. Despite known limitations, most chemotherapy dosing is mostly done by body surface area (BSA). Sarcopenia is one such limitation. Sarcopenia includes loss of skeletal muscle mass, low muscle density, low muscle strength and fat infiltration of muscle. Sarcopenia (especially loss of skeletal muscle mass) is the predominant feature of cancer cachexia. Sarcopenia is associated with poor prognosis, possibly because sarcopenia reflects an aggressive phenotype of cancer or patient co-morbidities.
Clinically, sarcopenia is usually assessed by measuring muscle and fat composition on cross sectional imaging via CT at level of L3 vertebrae. The correlation between body mass index (BMI) and sarcopenia is poor and many obese patients are also sarcopenic. Further, there is great variation in lean body mass for patients with the same BSA. Of patients with cancer, up to 50% have sarcopenia and 10% have sarcopenic obesity. Furthermore, up to 25% of obese cancer patients will be sarcopenic.
Sarcopenia and sarcopenic obesity have been associated with increased chemotherapy toxicity in a number of solid organ malignancies (including oesophageal, breast, lung, pancreas, renal, melanoma and colorectal) and with a number of chemotherapy agents (5FU, platinums, taxanes, anthracyclines, gemcitabine) and, to some extent, tyrosine kinase inhibitors (sunitinib, sorafenib, vandetanib, afatinib). The data linking sarcopenia and toxicity from immunotherapy is less well established. Generally, sarcopenic obese have higher toxicity and poorer prognosis than either (i) sarcopenic but non-obese patients and (ii) obese but non-sarcopenic patients. The reasons why sarcopenic patients have higher toxicity are not clear but probably relate to pharmacokinetic changes.
Despite this, there are barriers to routine dosing based on sarcopenia such as limit of high quality data on efficacy of dosing based on sarcopenia (especially in adjuvant setting), defining and measuring sarcopenia and lack of mechanisms by which to adjust dose in sarcopenic patients. There is also a paucity of evidence of the impact of sarcopenia on flat dosing drugs such as targeted therapy and many immunotherapies. Further study and development of dosing guidelines for patients with sarcopenia would be beneficial.