山梨医科大学雑誌　第7巻3号　089-095(1992)

Clinical Trial of Repetitive Portal Administration of Anticancer Drug as
a Prophylactic Modality for Liver Metastasis
- A Pilot Study of the Optimal Dosage and Reduced Toxicity -

Hiroshi NAKAGOMI, Masaru IWASAKI, Kunio TAKANO, Tetsunosuke MATSUKAWA, Akira UENO,
and Nobutaka UMEKITA

Abstract: Since 1986, we have been investigating repetitive intraportal administration of anticancer agents as prophylaxis for liver metastasis after gastrointestinal cancer surgery. Intraportal mitomycin C (MMC: 4 mg) was given on the day of operation and on postoperative days 1-6.
A preliminary pharmacokinetic study of intraportal MMC administration was performed in a rabbit model. A high first-pass extraction ratio was found at doses of 0.05 and 0.1 mg/kg, and it decreased at the higher doses of 0.2 and 0.4 mg/kg. The clinical dose of 4 mg corresponded to 0.05-0.1 mg/kg in the rabbit model and was considered to be within the optimal dose range.
The side effects and clinical outcome for patients treated with intraportal MMC were compared with those for a control group. The controls included an MMC (+) group that received intravenous MMC, and a MMC (-) group that did not. The intraportal MMC group showed less toxicity compared with the MMC (+) group and a prospective effect on survival and liver metatstasls.
These results suggested that our schedule for repetitive intraportal MMC was adequate.

Key words: Repetitive portal administration, Mitomycin C, Pharmacokinetic study




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