Influence of dosing schedules on toxicity and antitumour effects of combined cisplatin and docetaxel treatment in mice

Ayumi Kodama, Hideto To, Tomohiro Kinoshita, Ichiro Ieiri, Shun Higuchi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objectives: The combination of cisplatin and docetaxel shows a better cure rate against non-small-cell lung cancer than other drug combinations in clinical studies; however, severe myelosuppression and nephrotoxicity are dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule to reduce adverse effects and improve the antitumour effects. Methods: Cisplatin and docetaxel were administered i.p. to male ICR mice simultaneously, or sequentially with either cisplatin or docetaxel first followed by the second drug 12 h later (docetaxel-cisplatin and cisplatin-docetaxel groups). Antitumour effects of these schedules were also tested in C57BL/6N mice bearing Lewis lung carcinomas. Key findings: The simultaneous docetaxel/cisplatin group showed the lowest survival rate and the highest blood urea nitrogen (BUN) concentration. Cisplatin concentrations in the plasma and kidney were higher in the simultaneous dosing group than the sequential dosing groups. Antitumour effect was the greatest in the docetaxel-cisplatin group. Conclusions: The docetaxel-cisplatin regimen inhibited tumour growth the best and reduced mortality and nephrotoxicity.

Original languageEnglish
Pages (from-to)615-621
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume61
Issue number5
DOIs
Publication statusPublished - Jan 1 2009

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this