論文

査読有り 国際誌
2019年10月

Pharmacokinetics of thiotepa in high-dose regimens for autologous hematopoietic stem cell transplant in Japanese patients with pediatric tumors or adult lymphoma.

Cancer chemotherapy and pharmacology
  • Eisei Kondo
  • ,
  • Takashi Ikeda
  • ,
  • Hiroaki Goto
  • ,
  • Momoko Nishikori
  • ,
  • Naoko Maeda
  • ,
  • Kimikazu Matsumoto
  • ,
  • Hideo Kitagawa
  • ,
  • Naoto Noda
  • ,
  • Saori Sugimoto
  • ,
  • Junichi Hara

84
4
開始ページ
849
終了ページ
860
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00280-019-03914-2

PURPOSE: Thiotepa is used in high-dose chemotherapy (HDT) before autologous hematopoietic stem cell transplantation (HSCT) to treat solid tumors and hematological malignancies. This Phase 1 study was conducted to establish the pharmacokinetics (PK) of thiotepa in a Japanese population. METHODS: HDT/HSCT was performed in pediatric patients (≥ 2 years) with solid tumors or brain tumors (thiotepa 200 mg/m2/day IV-infused over 24 h on HSCT Days - 12, - 11, - 5, and - 4 and melphalan 70 mg/m2/day IV-infused over 1 h on Days - 11, - 5, and - 4) and adult patients (≥ 16 years) with malignant lymphoma (thiotepa 200 mg/m2/day 2-h IV-infusion on HSCT Days - 4 and - 3 plus busulfan 0.8 mg/kg 2-h IV-infusion every 6 h from HSCT Days - 8 to - 5). Pharmacokinetics of thiotepa were assessed following initial dose. Safety and efficacy were also evaluated. RESULTS: Nine pediatric and 10 adult patients were enrolled. Mean volume of distribution (Vz) of thiotepa normalized with body surface area (BSA) was lower for pediatric patients (16.4 L/m2) compared with adult patients (26.4 L/m2) as expected due to the higher specific surface area of children. Clearance and biological half-life were similar between pediatric and adult patients. Two serious adverse events (cardiac arrest and pulmonary edema) were observed. Survival rate (Day 100 post-HSCT) was 77.8% (95% CI 36.5-93.9%) for pediatric patients and 100% for adult patients. CONCLUSION: Thiotepa elimination was comparable in pediatric and adult patients with cancer. Lower Vz in pediatric compared with adult patients was expected. HDT with thiotepa prior to autologous HSCT was well tolerated. STUDY REGISTRATION: Japic CTI-163433.

Web of Science ® 被引用回数 : 2

リンク情報
DOI
https://doi.org/10.1007/s00280-019-03914-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31428821
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768914
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000488659900018&DestApp=WOS_CPL
URL
http://orcid.org/0000-0003-0995-9405

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