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Methotrexate bound to carbon particles used for treating cancers with lymph node metastases in animal experiments and
A Hagiwara1, T Takahashi, K Sawai
1Kyoto Prefectural University of Medicine, Kyoto, Japan.
Background:
A new dosage formulation, methotrexate adsorbed onto activated carbon particles (MTX-CH), was developed for treating cancer patients with lymph node metastases.
Methods:
MTX-CH injected subcutaneously into the left hind foot pad of rats delivered greater amounts of methotrexate selectively to the regional lymph nodes and to the injection site for longer periods than did the same dose of methotrexate in aqueous solution. Seven days after mice received a subcutaneous inoculation with 5 x 10(5) P388 leukemia cells in the left hind foot pad, when metastasis had occurred in the left popliteal lymph node, methotrexate was injected subcutaneously into the left hind foot pad in the form of either MTX-CH or methotrexate aqueous solution. In clinical trials, patients with cancers in relatively early stages (5 patients with gastric cancer and 1 with esophageal cancer) each received local injections of MTX-CH doses of 250 to 500 mg under fiberscope.
Results:
MTX-CH extended the survival time better than did methotrexate aqueous solution. In mice who received an inoculation of P388 leukemia cells and drug treatment using the same procedures, the treatment effects on metastases to the regional lymph nodes were significantly greater in mice treated with the MTX-CH than in those given methotrexate aqueous solution. MTX-CH controlled the disease well for 25 to 35 months.
Conclusions:
Local injection of MTX-CH is apparently useful for treating digestive cancers with lymph node metastases in patients who have difficulty tolerating surgery.