Preclinical in vivo activity of a combination gemcitabine/liposomal doxorubicin against cisplatin-resistant human ovarian cancer (A2780/CDDP)
Autor: | Salvatore Mancuso, Giovanni Scambia, E. Fruscella, Cristiano Ferlini, Daniela Gallo, Patrizia Apollonio |
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Rok vydání: | 2006 |
Předmět: |
Combination therapy
medicine.medical_treatment Transplantation Heterologous Mice Nude Pharmacology Deoxycytidine Sensitivity and Specificity Mice Random Allocation In vivo Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Survival rate Probability Ovarian Neoplasms Chemotherapy Dose-Response Relationship Drug business.industry Obstetrics and Gynecology medicine.disease Gemcitabine Transplantation Survival Rate Disease Models Animal Oncology Doxorubicin Drug Resistance Neoplasm Toxicity Liposomes Female Cisplatin Ovarian cancer business Neoplasm Transplantation medicine.drug |
Zdroj: | International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 16(1) |
ISSN: | 1048-891X |
Popis: | Both gemcitabine and liposomal doxorubicin are antineoplastic drugs with clinical activity in platinum-refractory ovarian cancer. The purpose of this study was to evaluate the antitumor activity of a combination gemcitabine/liposomal doxorubicin administered to athymic mice bearing cisplatin-resistant human ovarian cancer (A2780/CDDP) xenografts. Emphasis was on the use of very low doses of each drug and of different dosing schedules. Data obtained showed that combined treatment with 80 mg/kg gemcitabine and 15 mg/kg liposomal doxorubicin produced a significant enhancement of antitumor activity compared with monotherapy at the same doses of these agents. Noteworthy is the fact that the majority of xenograft-bearing animals receiving the combination therapy demonstrated a complete tumor regression at the end of the study. A similar trend was observed when doses of both drugs were reduced to 20 mg/kg gemcitabine and to 6 mg/kg liposomal doxorubicin. Again, three out of ten mice receiving the combination were tumor free at the end of the study. No significant differences were observed in antitumor activity when comparing the simultaneous vs the consecutive dosing schedule. Remarkably, no additive toxicity was observed in any experimental trials. These data encourage clinical trials to prove the advantages of this combination treatment with respect to the single-agent chemotherapy in platinum-refractory ovarian cancer patients. |
Databáze: | OpenAIRE |
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