Pharmacokinetics and toxicity of 120-hour continuous-infusion hydroxyurea in patients with advanced solid tumors

Edward M. Newman, Mary Carroll, Steven A. Akman, Warren Chow, Paul Coluzzi, Victor Hamasaki, Lucille A. Leong, Kim A. Margolin, Robert J. Morgan, James W. Raschko, Stephen Shibata, George Somlo, Merry Tetef, Yun Yen, Chul W. Ahn, James H. Doroshow

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17 引文 斯高帕斯(Scopus)

摘要

A group of 18 patients with advanced cancer were entered on a phase I study of a 120-h continuous intravenous infusion of hydroxyurea. The dose of hydroxyurea was escalated in cohorts of patients from 1 to 2 to 3.2 g/m2 per day. The primary dose-limiting toxicity was neutropenia, often accompanied by leukopenia, thrombocytopenia and generalized skin rash. Prophylactic treatment of patients with dexamethasone and diphenhydramine hydrochloride prevented the skin rash, but not the hematopoietic toxicities. The pharmacokinetics of hydroxyurea were studied in all patients. The steady-state concentrations of hydroxyurea were linearly correlated with the dose (R2 = 0.71, n = 18, P < 0.0001). The mean ± SE concentrations were 93 ± 16, 230 ± 6 and 302 ± 27 μM at 1, 2 and 3.2 g/m2 per day, respectively. The mean ± SE renal and nonrenal clearances of hydroxyurea were 2.14 ± 0.18 and 3.39 ± 0.28 l/h per m2 (n = 16), neither of which correlated with the dose. The concentration of hydroxyurea in plasma decayed monoexponentially with a mean ± SE half-life of 3.25 ± 0.18 h (n = 17). The steady-state concentration of hydroxyurea was >200 μM in all nine patients treated at 2 g/m2 per day, a dose which was well tolerated for 5 days. We recommend this dose for phase II trials in combination with other antineoplastic agents.

原文英語
頁(從 - 到)254-258
頁數5
期刊Cancer Chemotherapy and Pharmacology
39
發行號3
DOIs
出版狀態已發佈 - 1997
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 毒理學
  • 藥理
  • 癌症研究
  • 藥學(醫學)

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