Evaluation of successful treatment of malignant pleural mesothelioma mouse model by intra-pleural new anti-drug (pemetrexed) administration

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We evaluated the anti-proliferative effects of cisplatin, gemcitabine and pemetrexed alone and in combination with gemcitabine, pemetrexed with malignant pleural mesothelioma cell line (H28, 211H). As a result, in combination with gemcitabine, pemetrexed, additional effect was not recognized.We injected 0, 25, 125, 250, 500, 1000, 1500 mg/kg pemetrexed into the pleural cavity of mouse. The next day, average body weight was decreased 2.3%, thereafter, average body weight increased favorably. This tendency was not depend on the amount of pemetrexed. Death by overdose of pemetrexed in single injection was not recognized.Next, we injected 0, 100, 250, 500, 750, 1000 mg/kg pemetrexed into the pleural cavity of mouse once a week for three consecutive weeks. The average weight of each group increased favorably and there was no significant difference. Namely, we could not find the correlation between the weight loss and the amount of pemetrexed by intra-pleural pemetrexed administration. This … More result is different from the case of docetaxel that we evaluated before.We injected 211H into the pleural cavity of mouse. After one week, we started repeated administration of pemetrexed or SB (one of histone deacetylase inhibitor (HDAC)) once a week for three consecutive weeks.We divided seven groups. We injected 0, 100, 1000 mg/kg pemetrexed, 20 mg SB, 100 mg/kg pemetrexed combined with 20 mg SB into the pleural cavity 100, 1000 mg/kg pemetrexed into abdominal cavity. Between each group, there was no significant difference in overall survival time. On the average body weight of the group that was injected pemetrexed into the pleural cavity 100 mg/kg and the group that was injected 1000 mg/kg pemetrexed injected into the pleural cavity, there was no significant difference.However, the average body weight of the group that was injected 100 mg/kg pemetrexed into the pleural cavity was significantly heavy than the group that was injected 100 mg/kg pemetrexed into the abdominal cavity.These results may suggest that the side effect of intra-pleural pemetrexed administration is less than that of intra-abdominal pemetrexed administration. Less