Targretin has indicated chemotherapeutic activity against
nonsmall-cell lung cancer and
chemoprevention in rat mammary gland. Therefore,
targretin was evaluated for the prevention of 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanol (NNK) and
vinyl carbamate-induced lung
tumors in female strain A mice. Three experiments were performed: (i) a dose-response study with
vinyl carbamate-induced
tumors; (ii) a limited treatment study also with
vinyl carbamate and (iii) prevention of NNK-induced
tumors. In the dose-response study, 0, 10, 30, 100 and 300 mg/kg
targretin were administered after
vinyl carbamate. Dose levels of 30 mg/kg and greater significantly decreased
tumor multiplicity by >19%. However, the efficacy of 30 and 300 mg/kg was not significantly different demonstrating a shallow dose-response relationship. In the limited treatment study, 200 mg/kg
targretin was administered to the mice from 4-13, 4-19, 4-25 and 23-25 weeks after
vinyl carbamate. Administering
targretin from weeks 4-19 and 4-25 decreased the multiplicity of
tumors from 35.3 +/- 1.43 to 29.1 +/- 1.51 and 25.0 +/- 0.93, respectively, and along with administering it from weeks 23-25 decreased
tumor size. In the third study, when
targretin (100 and 300 mg/kg) was administered for 3 weeks after NNK followed by a 20 weeks holding period,
tumor multiplicity was reduced from 10.6 +/- 1.13 to 6.38 +/- 0.75 and 4.60 +/- 0.70, respectively. Hence,
targretin demonstrated both preventive and therapeutic activity with respect to mouse lung
tumors supporting its further development as a preventive and therapeutic agent for
lung cancer.