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Metronomic oral paclitaxel shows anti-tumor effects in an orthotopic mouse model of ovarian cancer

Journal of Gynecologic Oncology 2014년 25권 2호 p.130 ~ p.135

한호섭(Hahn Ho-Suap) - Kwandong University College of Medicine Cheil General Hospital & Women’s Healthcare Center Department of Obstetrics and Gynecology
이기헌(Lee Ki-Heon) - Kwandong University College of Medicine Cheil General Hospital & Women’s Healthcare Center Department of Obstetrics and Gynecology
이인호(Lee In-Ho) - Kwandong University College of Medicine Cheil General Hospital & Women’s Healthcare Center Department of Obstetrics and Gynecology
이제호(Lee Jae-Ho) - Cheil General Hospital and Women’s Health Care Center Laboratory of Molecular Oncology
(Whang Chang-Sung) - Cheil General Hospital and Women’s Health Care Center Human Resource Bank
조영우(Jo Yeong-Woo) - Hoengseong Daehwa Pharm. Co Research & Development Center
김태진(Kim Tae-Jin) - Kwandong University College of Medicine Cheil General Hospital & Women’s Healthcare Center Department of Obstetrics and Gynecology

Abstract

Objective: The purpose of this study was to compare the in vivo anti-tumor efficacy of a mucoadhesive, lipid-based, oral paclitaxel formulation (DHP107) with traditional, intraperitoneal (IP) paclitaxel using an orthotopic mouse model of chemotherapy-sensitive SKOV3ip1 ovarian cancer.

Methods: To determine the optimal therapeutic dose of oral paclitaxel, DHP107 was administered per os to female athymic nude mice at 0, 25, or 50 mg/kg twice per week. Control mice received 100 μL saline once per week. IP injections of paclitaxel at 5 mg/kg once per week were used for comparison. To evaluate the potential therapeutic effect of metronomic DHP107 chemotherapy, mice received DHP107 50 mg/kg once per week per os, which was compared with 25 mg/kg twice per week and with vehicle-treated controls.

Results: Low-dose DHP107 (25 mg/kg) twice per week was as effective as IP paclitaxel (5 mg/kg once a week) but high-dose DHP107 (50 mg/kg once per week) was less effective at inhibiting tumor growth in an orthotopic mouse model (88%, 82%, and 36% decrease in tumor weight, respectively). Mice that received 25 mg/kg DHP107 twice per week or 50 mg/kg DHP107 once per week per os had a significant decrease in tumor weight compared with vehicle-treated controls (p<0.01, both doses).

Conclusion: Metronomic oral chemotherapy with DHP107 showed anti-tumor efficacy in vivo similar to IP paclitaxel in an orthotopic mouse model.