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Preclinical combination therapy of the investigational drug NAMI-A with doxorubicin for mammary cancer.
- Source :
- Investigational New Drugs; Feb2015, Vol. 33 Issue 1, p53-63, 11p
- Publication Year :
- 2015
-
Abstract
- Aim of the study The tumor metastases targeting ruthenium complex NAMI-A synergistically improves the activity of gemcitabine in combination therapies. High-throughput screening was used to identify other potential drug combinations from a library of FDA approved drugs. Doxorubicin was identified as a hit compound and was therefore evaluated in combination with NAMI-A in vitro and in a preclinical in vivo model. Results High-throughput screening identified eight structurally diverse compounds that synergize with NAMI-A including doxorubicin. The combination index on MCF-7 cells showed synergism as the concentration of NAMI-A increases independent of the doxorubicin concentration. In MCa mammary carcinoma of CBA mice, NAMI-A (35 mg/kg/day i.p. on days 7-12) followed by doxorubicin (10 mg/kg i.p. on day 16), significantly increased the effects of the individual drugs on metastases with 70 % animals resulting free of macroscopically detectable tumor nodules in the lungs at sacrifice. NAMI-A, unlike doxorubicin, cured 60 % of the treated mice but the combination therapy was toxic to the animals. Conclusions The combined therapy of NAMI-A with doxorubicin synergizes on lung metastasis in a preclinical mouse model. The combination therapy at the maximum tolerated doses of the two drugs is toxic. Hence, this combination is not suitable for clinical studies using maximum tolerated doses. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANTINEOPLASTIC agents
INVESTIGATIONAL drugs
ANALYSIS of variance
ANIMAL experimentation
BIOPHYSICS
BREAST tumors
CELL lines
COMBINATION drug therapy
DOXORUBICIN
RESEARCH methodology
MICE
RESEARCH funding
STATISTICS
T-test (Statistics)
DATA analysis
TREATMENT effectiveness
IN vitro studies
THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 01676997
- Volume :
- 33
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Investigational New Drugs
- Publication Type :
- Academic Journal
- Accession number :
- 100421308
- Full Text :
- https://doi.org/10.1007/s10637-014-0175-5