1993 Fiscal Year Final Research Report Summary
Enhanced therapeutic effects and reduced toxicity on perito-toneal carcinomatosis by use of anti-cancer drugs incorporated in microshperes
| Project/Area Number |
04670795
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Kyoto Prefectural University of Medicine, Faculty of Medicine |
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Principal Investigator |
HAGIWARA Akeo Institution, Department, Title of Position Kyoto Prefectural University of Medicine, Faculty of Medicine, Assistant, 医学部, 助手 (90198648)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toshio Institution, Department, Title of Position Kyoto Prefectural University of Medic, 医学部, 教授 (50079828)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Microspheres / Peritoneal Carcinomatosis / Anti-Cancer Drugs / Drug-Delivery-System |
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| Research Abstract |
A new drug-delivery formulation of cisplatin, whereby cisplatin was incorporated in lactic acid oligomer microspheres (CDDP-MS), was developed in a dosage form for peritoneal carcinomatosis. In vitor study showed that CDDP-MS released 70% of the incorporated cisplatin slowly during a period of 3 weeks.
CDDP-MS resulted in a higher cisplatin concentration in tissue adjacent to the peritoneum for a longerperiod of time, and the concentration of cisplatin in the rest of the body was lower than that delivered by the cisplatin solution.
The 50% lethal dose value, determined by the Litchfield-Wilcoxon method in mice was 23.8 mg/kg in CDDP-MS in terms of cisplatin, whereas in the cisplatin solution it was 13.5 mg/kg body weight.
CDDP-MS, tested in experimental peritoneal carcinomatosis induced by transplantable M 5076 tumor in mice, enhanced therapeutic effects when compared with the same toxicity dosage of cisplatin solution.
CDDP-MS, at cisplatin 100 mg/person, was given intraperitoneally to 14 patients and 200 mg/person to one patient for the treatment of malignant ascites. The ascites disappeared completely in 8 of the 15 patients, and partially in 5 patients, for an over-all response rate of 87%. The side effects were mild, and tolerable for patients.
Microspheres incorporating methotrexate or 5-FU were developed to release the incororating anti-cancer drugs slowly for a long period of time in vitro.
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