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在接受紫杉烷类和铂类药物诱导化疗的男性头颈部癌症患者中,每公斤去脂体重的化疗剂量增加了剂量限制毒性事件。

Chemotherapy dose per kilogram lean body mass increased dose-limiting toxicity event in male head and neck cancer with taxane and platinum-based induction therapy.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City, 81362, Taiwan (R.O.C.).

Department of Pharmacy, Tajen University, Pingtung, Taiwan.

出版信息

BMC Cancer. 2022 Oct 21;22(1):1084. doi: 10.1186/s12885-022-10152-y.

Abstract

BACKGROUND

This study aimed to determine whether drug doses per kilogram of lean body mass (LBM) were associated with dose-limiting toxicity (DLT) events in head and neck cancer (HNC) patients.

METHODS

This retrospective cohort study included 179 HNC patients who underwent induction chemotherapy (IC) at a medical center from May 1, 2014, to May 31, 2021. HNC patients' characteristics, tumor factors, IC regimen and dose, laboratory data, and body composition factors, including lean body mass (LBM) and skeletal muscle index (SMI), derived from CT, MRI, or PET scan images and drug dose per kilogram LBM were recorded. Dose-limiting toxicity (DLT) events were regarded as the primary outcome. Multivariate logistic regression was used to establish a novel risk score for DLT events by the abovementioned variables. The above-mentioned risk score was validated in another cohort.

RESULTS

The overall DLT events during the first cycle of IC for 179 HNC patients was 24%. After stratifying by gender, docetaxel per kilogram LBM > 2.52 mg/kg (adjusted odds ratio [aOR]: 3.18; 95% confidence interval [CI], 1.25-8.09), pre-treatment glutamic pyruvic transaminase (GPT) > 40 U/L (aOR, 2.61; 95% CI, 1.03-6.64), and history of chronic liver diseases (aOR, 3.98; 95% CI, 1.03-15.46) were significant variables in male HNC patients. The DLT events risk was categorized by summation of the above-mentioned risk factors for male HNC patients. Three risk groups were stratified by overall event of 17.6%, 25.8%, and 75%. The above-mentioned risk score had an acceptable discriminatory ability in another validation cohort.

CONCLUSIONS

Among male HNC patients treated with IC, docetaxel per kilogram LBM more than 2.52 mg/kg, pre-treatment GPT > 40 U/L, and history of chronic liver disease were significant risk factors for DLT events. Identifying high-risk patients could help physicians prevent severe/fatal complications among HNC patients undergoing IC, especially for the male individuals.

摘要

背景

本研究旨在确定头颈部癌症(HNC)患者每公斤去脂体重(LBM)的药物剂量是否与剂量限制毒性(DLT)事件相关。

方法

本回顾性队列研究纳入了 2014 年 5 月 1 日至 2021 年 5 月 31 日在一家医疗中心接受诱导化疗(IC)的 179 例 HNC 患者。记录了 HNC 患者的特征、肿瘤因素、IC 方案和剂量、实验室数据以及来自 CT、MRI 或 PET 扫描图像的身体成分因素,包括去脂体重(LBM)和骨骼肌指数(SMI)。将剂量限制毒性(DLT)事件视为主要结局。采用多变量逻辑回归分析,根据上述变量建立 DLT 事件的新风险评分。在另一个队列中验证了上述风险评分。

结果

179 例 HNC 患者第一周期 IC 期间总的 DLT 事件发生率为 24%。按性别分层后,每公斤 LBM 的多西他赛剂量>2.52mg/kg(调整后的优势比[aOR]:3.18;95%置信区间[CI],1.25-8.09)、治疗前谷氨酸丙酮酸转氨酶(GPT)>40U/L(aOR,2.61;95%CI,1.03-6.64)和慢性肝病史(aOR,3.98;95%CI,1.03-15.46)是男性 HNC 患者的显著变量。根据上述男性 HNC 患者的危险因素对 DLT 事件风险进行了分类。通过上述危险因素的总和,将男性 HNC 患者分为三个风险组,总事件发生率分别为 17.6%、25.8%和 75%。上述风险评分在另一个验证队列中具有可接受的鉴别能力。

结论

在接受 IC 治疗的男性 HNC 患者中,每公斤 LBM 的多西他赛剂量超过 2.52mg/kg、治疗前 GPT>40U/L 和慢性肝病史是 DLT 事件的显著危险因素。识别高危患者有助于医生预防 HNC 患者接受 IC 治疗时发生严重/致命并发症,尤其是男性患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f1/9587609/41da21ae5d64/12885_2022_10152_Fig1_HTML.jpg

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