Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models

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.