Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models.
BACKGROUND
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.
Herbst
R S
RS
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Takeuchi
H
H
Teicher
B A
BA
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000187:drug effects; D016190:Carboplatin / Q000008:administration & dosage; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003510:Cyclohexanes; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000008:administration & dosage; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D017239:Paclitaxel / Q000008:administration & dosage; D012717:Sesquiterpenes / Q000008:administration & dosage
D003510:Cyclohexanes; D012717:Sesquiterpenes; D016190:Carboplatin; D008911:Minocycline; D017239:Paclitaxel; D000077609:O-(Chloroacetylcarbamoyl)fumagillol