Schaeffers Anouk W M A, van Neerven Cassimy B, van Balen Dorieke, Crul Mirjam, Slingerland Marije, Luelmo Saskia A C, de Boer Jan Paul, Voortman Jens, van Zuilen Arjan D, de Bree Remco, Devriese Lot A
Department of Head and Neck Surgical Oncology, Division Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Pharmacology, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.
Br J Clin Pharmacol. 2025 Jul;91(7):1996-2007. doi: 10.1002/bcp.70015. Epub 2025 Feb 24.
The aim of this study was to determine if head and neck squamous cell carcinoma (HNSCC) patients treated with cisplatin chemoradiotherapy and short hydration (SH) experience less dose-limiting toxicity (DLT) and receive more cisplatin than those with medium hydration (MH) or long hydration (LH).
Baseline characteristics, cumulative cisplatin dose and toxicities were collected. Differences between LH, MH and SH were tested, with separate analyses for triweekly 100 mg/m cisplatin and weekly 40 mg/m cisplatin. Mixed models assessed the hydration schedule's effect on cumulative dose.
A total of 389 patients were included. DLT occurrence was comparable between hydration groups (P = .060), but DLT type differed (P = .007). Nephrotoxicity was common with LH and MH (n = 11, 61% and n = 26, 45%, respectively), and ototoxicity with SH (n = 35, 36%). DLT occurrence in triweekly patients differed between LH and MH (n = 18, 64% vs n = 25, 32%, P = .004), but not between MH and SH (P = .171) or LH and SH (P = .055) patients. Cisplatin dose differed between LH and MH (median 200 vs 300, P = .008) as well as between LH and SH (median 200 vs 300, P = .024) but not between MH and SH (P = .429) patients. Hydration had no effect on dose (F = 2.09, P = .125).
DLT cause differed between hydration groups, with less nephrotoxicity but more ototoxicity in HNSCC patients with SH. Triweekly cisplatin LH patients had more DLT and lower cumulative dose compared to MH and SH, but no hydration effect in general on dose was found.
本研究旨在确定接受顺铂同步放化疗及短程水化（SH）的头颈部鳞状细胞癌（HNSCC）患者与接受中程水化（MH）或长程水化（LH）的患者相比，是否经历更少的剂量限制性毒性（DLT）且接受更多的顺铂。
收集基线特征、顺铂累积剂量和毒性反应。对LH、MH和SH之间的差异进行检验，分别分析每三周一次100mg/m²顺铂和每周一次40mg/m²顺铂的情况。混合模型评估水化方案对累积剂量的影响。
共纳入389例患者。各水化组间DLT发生率相当（P = 0.060），但DLT类型不同（P = 0.007）。LH和MH组肾毒性常见（分别为n = 11，61%和n = 26，45%），SH组耳毒性常见（n = 35，36%）。每三周一次用药的患者中，LH和MH组间DLT发生率不同（n = 18，64%对n = 25，32%，P = 0.004），但MH和SH组间（P = 0.171）以及LH和SH组间（P = 0.055）无差异。LH和MH组间顺铂剂量不同（中位数200对300，P = 0.008），LH和SH组间也不同（中位数200对300，P = 0.024），但MH和SH组间无差异（P = 0.429）。水化对剂量无影响（F = 2.09，P = 0.125）。
各水化组间DLT原因不同，SH的HNSCC患者肾毒性较小但耳毒性较大。与MH和SH相比，每三周一次使用顺铂的LH患者DLT更多且累积剂量更低，但总体未发现水化对剂量有影响。
