Pancreatic cancer therapy with a novel pump for controlled drug release.
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.
Haramoto
Mari
M
Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Sakyoku, Kyoto, Japan.
Kohno
Masayuki
M
Nakajima
Oumi
O
Horibe
Tomohisa
T
Kiyohara
Masanobu
M
Fukazawa
Hirohide
H
Togawa
Tsuyoshi
T
Kawakami
Koji
K
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
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D005472:Fluorouracil