Continuous docetaxel chemotherapy improves therapeutic efficacy in murine models of ovarian cancer.
Ovarian cancer is known as the silent killer for being asymptomatic until late stages. Current first-line treatment consists of debulking surgery followed by i.v. chemotherapeutics administered intermittently, which leads to insufficient drug concentrations at tumor sites, accelerated tumor proliferation rates, and drug resistance, resulting in an overall median survival of only 2 to 4 years. For these reasons, more effective treatment strategies must be developed. We have investigated a localized, continuous chemotherapy approach in tumor models of human and murine ovarian cancers using the antineoplastic agent docetaxel. We show here that continuous docetaxel therapy is considerably more efficacious than intermittent therapy, resulting in a greater decrease in tumor burden and ascites fluid accumulation. Immunohistochemical analyses show that continuous chemotherapy abrogates tumor cell proliferation and angiogenesis to the tumor microenvironment, leading to greater tumor cell death than intermittent docetaxel therapy. Overall, our results show greater therapeutic advantages of continuous over intermittent chemotherapy in the treatment of ovarian cancer.
Department of Pharmaceutical Sciences, University of Toronto, Ontario, Canada.
Raquel
R
De Souza
Payam
P
Zahedi
Eduardo H
EH
Moriyama
Christine J
CJ
Allen
Brian C
BC
Wilson
Micheline
M
Piquette-Miller
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001201:Ascites / Q000150:complications / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D051379:Mice; D009389:Neovascularization, Pathologic / Q000150:complications / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel