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


CONCLUSIONS
Metronomic oral chemotherapy with DHP107 showed anti-tumor efficacy in vivo similar to IP paclitaxel in an orthotopic mouse model.
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Ho-Suap
HS
Hahn
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Ki-Heon
KH
Lee
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
In-Ho
IH
Lee
Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Jae-Ho
JH
Lee
Human Resource Bank, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Chang-Sung
CS
Whang
Research & Development Center, Daehwa Pharm. Co., Hoengseong, Korea.
Yeong-Woo
YW
Jo
Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Tae-Jin
TJ
Kim
Chemotherapy; DHP107; Oral paclitaxel; Ovarian cancer