Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models (original) (raw)
Abstract
Introduction: With the introduction of new drugs, the efficacy of chemotherapy in non-small-cell lung cancer has been improving. The combination of paclitaxel and carboplatin has shown activity in this disease but is far from curative. Methods: The antiangiogenic agent regimen of TNP-470/minocycline was added to treatment with paclitaxel and carboplatin alone and in combination in animals bearing the Lewis lung carcinoma. Results: Administration of the antiangiogenic regimen prior to, during and after the cytotoxic therapy increased the tumor growth delay 1.6-fold and decreased the number of lung metastases to 20% of the number observed in the control animals. [14C]Paclitaxel, platinum from carboplatin and [14C]albumin levels were determined over a 24-h time course in tumors and normal tissues of animals bearing the Lewis lung carcinoma and pretreated with TNP-470/minocycline or not pretreated. There were higher levels of [14C]paclitaxel, platinum from carboplatin and [14C]albumin in the tumors and some normal tissues of the animals that had received TNP-470/minocycline compared with those that had not received TNP-470/minocycline, especially at the earlier time points. Administration of TNP-470/minocycline to animals bearing the EMT-6 mammary carcinoma increased the cytotoxicity of high-dose paclitaxel toward EMT-6 tumor cells and toward bone marrow CFU-GM. Administration of TNP-470/minocycline to animals bearing the EMT-6 mammary carcinoma also increased the cytotoxicity of carboplatin toward the EMT-6 tumor cells but did not affect the toxicity of carboplatin toward the bone marrow CFU-GM. Conclusions: The addition of TNP-470/minocycline to treatment with paclitaxel and carboplatin resulted in increased antitumor activity and efficacy and further investigation of this combination is warranted.
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Authors and Affiliations
- Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA, , , , , , US
Roy S. Herbst, Hideya Takeuchi & Beverly A. Teicher
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- Roy S. Herbst
You can also search for this author inPubMed Google Scholar - Hideya Takeuchi
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Received: 11 June 1997 / Accepted: 8 October 1997
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Herbst, R., Takeuchi, H. & Teicher, B. Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models.Cancer Chemother Pharmacol 41, 497–504 (1998). https://doi.org/10.1007/s002800050773
- Issue Date: March 1998
- DOI: https://doi.org/10.1007/s002800050773