基礎研究を基盤とした至適抗癌剤併用療法の構築

• 藤 秀人

  長崎大学医学部·歯学部附属病院薬剤部

書誌事項

タイトル別名

• Optimization of Combination Chemotherapy with Anti-Tumor Drugs Based on Experimental Animal Study

抄録

Metastatic breast cancer (MBC) is almost always incurable and median survival is 18-24 months.Although the combination of adriamycin (ADR) and docetaxel (DOC) has demonstrated higher efficacy against MBC,severe myelosuppression and cardiotoxicity have been dose-limiting factors.The purpose of this study was to devise an optimal dosing-schedule for this combination which lessens the severity of adverse effects and enhances antitumor effects.<br>(I) Dosing-sequence : <br>Mice were assigned to a simultaneous dosing group (ADR/DOC ; regimen commonly used in clinical practice) in which both drugs were administered simultaneously and 2 intermittent dosing groups (ADR-DOC and DOC-ADR) in which the second drug was administered 12 hours after the first one.In the DOC-ADR group,as compared to the ADR/DOC group,in addition to there being significantly less leukopenia and toxic death,the tumor growth inhibition rate was significantly higher.<br>(II) Dosing-interval : <br>When dosing intervals were varied in the 6-24 hour range in the DOC-ADR group,on day 21,body weights were markedly lower for doing intervals of 6 and 24 hours than they were for a dosing interval of 12 hours.<br>(III) Dosing-time : <br>For a group treated with ADR and one treated with DOC,adverse effects were least when the dosing times were 21 : 00 and 9 : 00,respectively.In a DOC (9 : 00)-ADR (21 : 00) group in which DOC was administered at 9 : 00 followed by ADR at 21 : 00 both body weight loss and leukopenia were significantly reduced as compared with a DOC (21 : 00)-ADR (9 : 00) group in which DOC was administered at 21 : 00 followed by ADR at 9 : 00.<br>These findings show that the therapeutic index of combination chemotherapy can be improved by choosing an optimal dosing-schedule.

収録刊行物

• 医療薬学

  医療薬学 33 (11), 897-904, 2007

  一般社団法人日本医療薬学会

キーワード

• combination chemotherapy
• dosing-sequence
• dosing-interval
• dosing-time
• adriamycin
• docetaxel

詳細情報

• CRID: 1390001204774967808
• NII論文ID: 110006452666
• NII書誌ID: AA11527197
• DOI: 10.5649/jjphcs.33.897
• ISSN: 18821499
• ISSN: 1346342X
• Web Site: http://dl.ndl.go.jp/info:ndljp/pid/10559199
• Web Site: https://search.jamas.or.jp/link/ui/2008116107
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • Crossref
  • NDL-Digital
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可