title: Pancreatic cancer therapy with a novel pump for controlled drug release.
abstract: Enhancing antitumor activity and minimizing treatment side effects are important issues in cancer therapy. One method to deal with these issues is the utilization of a drug delivery system (DDS). In this study, we developed a novel drug administration pump, a mechanically controlled DDS (M-DDS). The antitumor activity of 5-fluorouracil (5-FU) (15 or 30 mg/kg/day) was evaluated in comparison with systemic intraperitoneal (i.p.) administration for 7 days in a rat model of human pancreatic cancer. The M-DDS was superior to i.p. administration in enhancing antitumor activity and also prolonging median survival from 69 to 85 days at the lower drug dose (15 mg/kg/day). In addition, toxicities in liver, kidney and spleen were found in animals receiving i.p. administration, whereas rats receiving M-DDS treatment did not show these toxicities. The concentration of 5-FU in tumors 1 day after the completion of treatment was considerably higher in rats receiving M-DDS treatment. These results suggest that this novel M-DDS may be a powerful tool for the treatment of pancreatic cancer in combination with conventional chemotherapeutic drugs, offering strong antitumor activity with fewer toxicities. This novel M-DDS, consisting of a control circuit and drug reservoir/pump unit, may be a useful tool for the treatment not only of pancreatic cancer but also of various other accessible cancers for which there is no effective treatment, such as bile-duct and brain tumors.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Sakyoku, Kyoto, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Haramoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohno
authors.forename: Oumi
authors.initials: O
authors.lastname: Nakajima
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Horibe
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kiyohara
authors.forename: Hirohide
authors.initials: H
authors.lastname: Fukazawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Togawa
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D015918:Infusion Pumps, Implantable; D008297:Male; D008954:Models, Biological; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D051381:Rats; D011923:Rats, Nude; D016019:Survival Analysis; D014018:Tissue Distribution; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D005472:Fluorouracil