J Gynecol Oncol.  2014 Apr;25(2):130-135. 10.3802/jgo.2014.25.2.130.

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

• Hahn HS
• Lee KH
• Lee IH
• Lee JH
• Whang CS
• Jo YW
• Kim TJ

• KMID: 1708336
• DOI: http://doi.org/10.3802/jgo.2014.25.2.130

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 microL 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.

Keyword

Chemotherapy; DHP107; Oral paclitaxel; Ovarian cancer

MeSH Terms

Animals
Drug Therapy
Female
Humans
Mice*
Mice, Nude
Ovarian Neoplasms*
Paclitaxel*
Tumor Burden
Paclitaxel

Figure

• 

  Fig. 1 Paclitaxel (PTX) was injected intraperitoneal (IP) at doses of 1, 2.5, or 5 once per week into female athymic nude mice to determine the optimal therapeutic dose of IP PTX. Saline IP injections were used as control. (A) Body weight. (B) Tumor weight (*p<0.01). (C) Number of tumor nodules (†p<0.05).

• 

  Fig. 2 DHP107 was administered per os at 0, 25, or 50 mg/kg twice per week in female athymic nude mice to determine the optimal therapeutic dose of DHP107. Paclitaxel (PTX) intraperitoneal injections at 5 mg/kg were used for comparison. (A) Body weight. (B) Tumor weight (*p<0.01). (C) Number of tumor nodules (†p<0.02).

• 

  Fig. 3 To evaluate the potential therapeutic effect of DHP107 metronomic chemotherapy, mice were treated with DHP107 per os at 0 or 50 mg/kg once a week or 25 mg/kg twice per week. DHP107-1 and DHP107-2 represent DHP107 per os at 50 mg/kg once a week and DHP107 per os at 25 mg/kg twice per week, respectively. Paclitaxel (PTX) intraperitoneal injections at 5 mg/kg were used for comparison. (A) Body weight. (B) Tumor weight (*p<0.01). (C) Number of tumor nodules (†p<0.01).

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