Cisplatin pharmacokinetics and skeletal muscle mass in patients with head and neck cancer: is cisplatin overdosed in patients with low skeletal muscle mass?

Treatment of advanced stage head and neck squamous cell carcinoma (HNSCC) by chemoradiotherapy (CRT) with platinum-based chemotherapy is associated with frequent severe toxicity, requiring treatment de-escalation or termination of chemotherapy in at least 30% of patients. In recent years a relationship between low skeletal muscle mass, as measured using routine diagnostic CT scans, and chemotherapy related toxicity has been suggested in a variety of tumour types including HNSCC. A potential explanation for this relationship is that platinum compounds such as cisplatin are hydrophilic and only distribute into the fat-free body mass. Skeletal muscle mass is the largest contributor to fat-free mass. Chemotherapy dose is currently calculated using a patient’s body surface area (BSA), which does not take into account abnormal body composition. The hypothesis of this study is that cisplatin pharmakinetic parameters have a stronger association with skeletal muscle mass than with BSA. It is possible that the current chemotherapy dosing method using BSA insufficiently takes into account individual differences in body composition, and that cisplatin is relatively overdosed in patients with low skeletal muscle mass. This study will investigate the association between cisplatin pharmacokinetics and skeletal muscle mass, and the correlation between cisplatin pharmacokinetics and BSA. Secondary, this study will investigate the association between cisplatin pharmacokinetics and chemotherapy related toxicity including dose-limiting toxicity and quality of life.

In recent years a relationship between low skeletal muscle mass, as measured using routine diagnostic CT scans, and chemotherapy related toxicity has been suggested in a variety of tumour types including head and neck squamous cell carcinoma (HNSCC). A potential explanation for this relationship is that platinum compounds such as cisplatin are hydrophilic and only distribute into the fat-free body mass. Skeletal muscle mass is the largest contributor to fat-free mass. Chemotherapy dose is currently calculated using a patient’s body surface area (BSA), which does not take into account abnormal body composition. The hypothesis of this study is that cisplatin pharmakinetic parameters have a stronger association with skeletal muscle mass than with BSA. It is possible that the current chemotherapy dosing method using BSA insufficiently takes into account individual differences in body composition, and that cisplatin is relatively overdosed in patients with low skeletal muscle mass.

- Baseline measurements of skeletal muscle mass, quality of life and other study related parameters before start of chemoradiotherapy

- One quality of life measurement during chemoradiotherapy

- One quality of life measurement after the end of chemoradiotherapy

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