Paclitaxel exposure-toxicity analysis reveals a pharmacokinetic determinant for dose-limiting neutropenia in East-Asian solid tumor patients: results from two prospective, phase II studies.

Autor:	Xue, Jinhui, He, Haipeng, Lin, Zuan, Wu, Yuehan, Lin, Yuehao, Zhao, Hongyun, Salamone, Salvatore J., Huang, Yan, Yang, Yunpeng, Fang, Wenfeng, Zhang, Yang, Hong, Shaodong, Ma, Yuxiang, Zhang, Li
Předmět:	LUNG cancer RESEARCH CARBOPLATIN CLINICAL trials RESEARCH methodology NEUTROPENIA LUNG tumors ANTINEOPLASTIC agents EVALUATION research COMPARATIVE studies RESEARCH funding EAST Asians PACLITAXEL NASOPHARYNX tumors LONGITUDINAL method
Zdroj:	Cancer Chemotherapy & Pharmacology; Sep2022, Vol. 90 Issue 3, p229-237, 9p
Abstrakt:	Purpose: The time of a paclitaxel (PTX) concentration remains above 0.05 μM (Tc > 0.05) has been associated with PTX-induced adverse effects in Caucasians, while limited studies were reported in Asians. This study was aimed to explore the characteristics of Tc > 0.05 and the relationship between PTX exposure and toxicity in East-Asian patients.Methods: This study was based on two prospective phase II clinical trials and patients with advanced nasopharyngeal cancer (NPC) and non-small cell lung cancer (NSCLC) who were naïve to PTX were included independently. Eligible patients receive PTX (175 mg/m2) and carboplatin (AUC = 5) treatment every 3 weeks. PTX pharmacokinetic analysis was accessed. The relationship between PTX exposure and toxicities after first cycle as well as clinical efficacy was evaluated.Results: A total of 93 NPC and 40 NSCLC patients were enrolled. PTX exposure was consistent in two trials with average Tc > 0.05 duration of 38.8 h and 38.4 h, respectively. Average Tc > 0.05 in patients with grade 3/4 neutropenia was significantly higher than those without severe neutropenia in NPC patients (P = 0.003) and NSCLC patients (P = 0.007). Cut-off value of Tc > 0.05 were identified from the NPC cohort and then verified in the NSCLC cohort, dividing patients into high exposure Tc > 0.05 group (> 39 h) and low exposure group (≤ 39 h). Incidence of grade 3/4 neutropenia were significantly higher in the high exposure group in NPC cohort (43.3% vs 10.0%, P < 0.001) and NSCLC cohort (42.1% vs 9.5%, P = 0.028). No significant relationship between Tc > 0.05 and efficacy were observed.Conclusion: Patients with PTX Tc > 0.05 duration above 39 h experience more severe neutropenia than those under 39 h. Prospective studies are needed to verify this threshold. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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