Preclinical anti-tumor activity of XR5944 in combination with carboplatin or doxorubicin in non-small-cell lung carcinoma
Anti-Cancer Drugs, ISSN: 0959-4973, Vol: 16, Issue: 9, Page: 945-951
2005
- 14Citations
- 3Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations14
- Citation Indexes14
- 14
- CrossRef12
- Captures3
- Readers3
Article Description
XR5944 (MLN944) is a novel bis-phenazine currently in phase I clinical trials that has demonstrated potent cytotoxic activity against a variety of tumor models. The combinations of XR5944 with carboplatin or doxorubicin were investigated in COR-L23/P human non-small-cell lung carcinoma (NSCLC) cells in vitro and the corresponding xenografts in vivo. In vitro cytotoxicity was evaluated by the sulforhodamine B assay and the drug interactions following simultaneous or sequential exposure were determined using median-effect analysis to calculate combination indices (CIs). XR5944 demonstrated potent cytotoxicity compared to either carboplatin or doxorubicin in COR-L23/P cells. Simultaneous or sequential exposure of XR5944 followed by carboplatin led to a synergistic response (CI < 1), whereas the reverse order of addition showed an additive or antagonistic response (CI ≤ 1). Sequential administration of doxorubicin followed by XR5944 demonstrated marginally improved cytotoxicity (CI = 1.31-0.77) than other schedules (CI = 1.50-1.22) relative to individual drugs. Anti-tumor activity against COR-L23/P xenografts in nude mice was enhanced by administration of XR5944 (2 or 5 mg/kg) immediately before carboplatin (50 mg/kg) compared to single-agent treatment at the same doses. Improved efficacy was also observed by sequential administration of 7 mg/kg doxorubicin 48 h before 2.5 or 5 mg/kg XR5944. No additional toxicity was observed with combinations compared to single-agent treatment alone as determined by body weights. These data suggest that combinations of XR5944 with carboplatin or doxorubicin are of significant interest for clinical use, and that the schedule of administration may be important for achieving clinical efficacy over single-agent therapy. © 2005 Lippincott Williams & Wilkins.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=26244460585&origin=inward; http://dx.doi.org/10.1097/01.cad.0000176499.17939.56; http://www.ncbi.nlm.nih.gov/pubmed/16162971; https://journals.lww.com/00001813-200510000-00006; https://dx.doi.org/10.1097/01.cad.0000176499.17939.56; https://journals.lww.com/anti-cancerdrugs/Abstract/2005/10000/Preclinical_anti_tumor_activity_of_XR5944_in.6.aspx
Ovid Technologies (Wolters Kluwer Health)
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