Divisions of Hematology/Oncology and Gerontology, Geriatrics, and Palliative Care, Institute of Cancer Outcomes and Survivorship, The University of Alabama at Birmingham, 1600 7th Avenue South, Lowder 500, Birmingham, AL, 35233, USA.
UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.
Cancer Chemother Pharmacol. 2018 Feb;81(2):413-417. doi: 10.1007/s00280-017-3487-2. Epub 2017 Nov 20.
Great heterogeneity exists in the ability of adults with cancer to tolerate chemotherapy. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The objective of this exploratory study was to examine the association of low skeletal muscle, commonly known as sarcopenia, on the pharmacokinetics (PKs) of 5-fluorouracil (5FU) in patients receiving FOLFOX for colorectal cancer.
We performed a secondary analysis of a completed multicenter trial that investigated PK-guided 5FU dosing in patients receiving mFOLFOX6 +/- bevacizumab for colorectal cancer. Cycle 1 PK samples were obtained 2-44 h after the start of the 5FU infusion (steady state).
No significant differences in first cycle 5FU area-under-the-concentration-time-curve (AUC) were found between sarcopenic and non-sarcopenic patients (17.3 vs. 19.3 AUC, p = 0.43). Patients with grade 3/4 toxicity had a higher dose of 5FU per kg lean body mass (LBM) (105 vs. 93 mg/kg, p = 0.06), most notably for hematological toxicities (110 vs. 94 mg/kg, p = 0.002); however, no correlation between the dose/LBM and 5FU AUC was found.
Although our results did not confirm the impact of low skeletal muscle on PKs of 5FU, further research exploring the impact of body composition on chemotherapy PKs and related toxicities is warranted with the potential for alternative dosing strategies in sarcopenic patients to reduce unnecessary toxicities while maintaining efficacy.
成人对化疗的耐受性存在很大差异。身体成分的变化可能会影响细胞毒性药物的代谢率，并导致观察到的化疗毒性的变化。本探索性研究的目的是研究低骨骼肌（通常称为肌肉减少症）与接受结直肠癌 FOLFOX 治疗的患者 5-氟尿嘧啶（5FU）药代动力学（PK）之间的关联。
我们对一项已完成的多中心试验进行了二次分析，该试验研究了接受 mFOLFOX6 +/-贝伐单抗治疗的结直肠癌患者的 PK 指导 5FU 剂量。第 1 周期 PK 样本在 5FU 输注开始后 2-44 小时（稳态）获得。
在肌肉减少症和非肌肉减少症患者之间，第 1 周期 5FU 浓度-时间曲线下面积（AUC）没有显著差异（17.3 与 19.3 AUC，p=0.43）。毒性 3/4 级的患者每公斤瘦体重（LBM）的 5FU 剂量更高（105 与 93 mg/kg，p=0.06），尤其是血液学毒性（110 与 94 mg/kg，p=0.002）；然而，未发现剂量/LBM 与 5FU AUC 之间存在相关性。
尽管我们的结果并未证实低骨骼肌对 5FU PK 的影响，但需要进一步研究探索身体成分对化疗 PK 和相关毒性的影响，对于肌肉减少症患者，有可能采用替代剂量策略来减少不必要的毒性，同时保持疗效。
