Effectiveness of various anthelmintics in the treatment of moniliformiasis in experimentally infected Wistar rats.

Humans occasionally become infected with acanthocephalans, particularly Moniliformis moniliformis. Although several anthelmintics have been used, no controlled studies have been conducted to assess the efficacy of common anthelmintics in the treatment of moniliformiasis. The effectiveness of pyrantel pamoate, ivermectin, praziquantel, niclosamide, thiabendazole, and mebendazole was evaluated in the treatment of moniliformiasis in laboratory-infected female Wistar rats. Pyrantel pamoate and ivermectin were wholly unsuccessful in the treatment of moniliformiasis. A single dose of thiabendazole lead to a 40% reduction and two doses lead to a 57% reduction of worm burden after 2 weeks. The most effective drug in the treatment of moniliformiasis in rats was mebendazole, for which two doses resulted in a 69% reduction in worm burden after 2 weeks; however, 50% of the rats receiving the treatment died within 2 weeks after first administration of the drug. Two surviving rats that had been treated with mebendazole exhibited evidence of hepatic dysfunction characterized by extremely elevated levels of alkaline phosphatase in conjuction with depressed serum albumin levels. It is hypothesized that Mo. moniliformis may metabolize the drug and release a metabolite that is highly toxic to the host. On the basis of these data, thiabendazole is recommended as the drug of choice for the treatment of human acanthocephaliasis until more extensive testing can be conducted.

Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma.

PURPOSE: Sorafenib tosylate (sorafenib, BAY 43-9006, Nexavar) is a multi-kinase inhibitor that targets tumor cell proliferation and angiogenesis. These studies evaluated the efficacy and tolerability of combinations of sorafenib plus agents used to treat non-small cell lung cancer (NSCLC) using preclinical models of that disease. METHODS: Intravenous (iv) vinorelbine and interperitoneal (ip) cisplatin were administered intermittently (q4d x 3) in combination with sorafenib administered orally (po) once daily for 9 days starting on the same day as the standard agent. In studies with sorafenib and gefitinib, both agents were administered po daily for 10 days starting on the same day. Treatment in all studies was initiated against established sc tumors, and each study was conducted in duplicate. Efficacy was assessed as the delay in tumor growth to a specified size (TGD). RESULTS: Vinorelbine (6.7 mg/kg) and sorafenib (40 mg/kg) produced TGDs of 2.4 and 7.8 days, respectively, in the NCI-H460 NSCLC model. Combination therapy produced a 10.0-day TGD with no increase in toxicity. Combination therapy in the NCI-H23 NSCLC model with the highest evaluated dose levels of sorafenib plus cisplatin was well tolerated and produced TGDs equivalent to those produced by cisplatin alone. Lower dose levels of each agent produced approximately additive TGD's. Combination therapy in the A549 NSCLC model with sorafenib and gefitinib produced TGDs equivalent to that produced by sorafenib alone with no toxicity. Tumor growth in the MDA-MB-231 mammary tumor model, that contains mutations in signal transduction proteins downstream of the EGF receptor (the target of gefitinib) was also inhibited by sorafenib, but not by gefitinib. CONCLUSION: Concurrent administration of sorafenib and vinorelbine, cisplatin or gefitinib was at least as efficacious as the individual agents alone and was well tolerated. These results support the inclusion of sorafenib in clinical trials in NSCLC employing combinations of both cytotoxic and cytostatic agents.