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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 de...

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Detalles Bibliográficos
Autores principales: Hahn, Ho-Suap, Lee, Ki-Heon, Lee, In-Ho, Lee, Jae-Ho, Whang, Chang-Sung, Jo, Yeong-Woo, Kim, Tae-Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996263/
https://www.ncbi.nlm.nih.gov/pubmed/24761217
http://dx.doi.org/10.3802/jgo.2014.25.2.130
Descripción
Sumario: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.