PMID: 11604553Oct 18, 2001Paper

Adaptive intrapatient dose escalation of cisplatin in patients with advanced head and neck cancer

Anti-cancer Drugs
J H SchellensJ Verweij

Abstract

The purpose of this study was to explore the feasibility and toxicity of intrapatient dose adjustment using predefined levels of exposure to cisplatin, with the ultimate goal to further improve the antitumor activity of the treatment. The primary parameter for adaptive dosing was the level of platinum DNA adducts in peripheral white blood cells (WBC) and the secondary parameter the area under the curve (AUC) of unbound platinum in plasma, which were determined during the applied courses. Target levels had been defined in a previously performed pharmacologic study. The concept of adaptive dosing was tested in 16 patients with locally advanced head and neck (H/N) cancer who would receive six weekly courses of cisplatin at a starting dose level of 80 mg/m(2), which was previously investigated in a phase II study. Forty-seven percent of patients received a dose increase varying from 10 to 40%. Only two patients had exposure levels significantly below the defined target levels for DNA adducts and AUC. The majority of patients reached the defined target levels by modest dose increases of 10-20% during course 2. Relevant but reversible ototoxicity (temporary grade 3 in two patients) and renal toxicity (temporary grade 2 in two other p...Continue Reading

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Citations

Mar 8, 2013·Hearing Research·Sofia Waissbluth, Sam J Daniel
Jan 18, 2014·International Journal of Clinical Pharmacy·Youssef BennisBertrand Pourroy
Apr 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Walter J LoosJaap Verweij
May 29, 2008·British Journal of Cancer·A C PieckU Jaehde
Dec 17, 2015·Expert Opinion on Drug Metabolism & Toxicology·Xi-Lin XuJian-Guo Jiang
Oct 16, 2018·Frontiers in Pharmacology·Zulfan ZazuliAnke-Hilse Maitland-van der Zee
Jul 30, 2019·Chemical Research in Toxicology·Luyu QiFuyi Wang

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