Rs. Herbst et al., PACLITAXEL CARBOPLATIN ADMINISTRATION ALONG WITH ANTIANGIOGENIC THERAPY IN NON-SMALL-CELL LUNG AND BREAST-CARCINOMA MODELS/, Cancer chemotherapy and pharmacology, 41(6), 1998, pp. 497-504
Introduction: With the introduction of new drugs, the efficacy of chem
otherapy in non-small-cell lung cancer has been improving. The combina
tion 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 carbop
latin alone and in combination in animals bearing the Lewis lung carci
noma. Results: Administration of the antiangiogenic regimen prior to,
during and after the cytotoxic therapy increased the tumor growth dela
y 1.6-fold and decreased the number of lung metastases to 20% of the n
umber observed in the control animals. [C-14]Paclitaxel, platinum from
carboplatin and [C-14]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 [C-14]paclitaxel, platinum from carboplati
n and [C-14]albumin in the tumors and some normal tissues of the anima
ls that had received TNP-470/minocycline compared with those that had
not received TNP-470/minocycline, especially at the earlier time point
s. 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 tre
atment with paclitaxel and carboplatin resulted in increased antitumor
activity and efficacy and further investigation of this combination i
s warranted.