[Targeting chemotherapy with activated carbon particles adsorbing anti-cancer drugs]

Abstract

A new drug delivery system comprising activated carbon particles adsorbing anticancer drugs was developed. Activated carbon particles have affinity to the regional lymph-nodes and the tumor surface. When activated carbon particles adsorbing anticancer drug were administered into the tissues or serosal cavity, they remained for a long time at the site of application, and released the drug slowly. Activated carbon particles adsorbing mitomycin C (MMC-CH) were prepared for the use of an intracavitary administration. In animal experiment tissues, MMC-CH distributed a large amount of mitomycin C to the intraperitoneal tissues, while there was a low level of mitomycin C in the whole body. The LD50 value of MMC-CH was 5.3 times as high as that of mitomycin C aqueous solution. The therapeutic index (LD50/ED50) of the MMC-CH therapy was 3.1 times higher than that of the mitomycin C aqueous solution in Yoshida sarcoma ascites. Clinical trials of MMC-CH were performed in 81 patients with malignant effusion. Fifty-one of the 81 patients responded well. Activated carbon particles adsorbing peplomycin (PEP-CH) were prepared for chemotherapy against lymphatic metastasis. A high level of peplomycin was distributed to regional lymph nodes for a long time, when it was injected into the gastric wall of dogs. In animal experiments using MH 134 tumor, the therapeutic efficacy of PEP-CH on the lymphatic metastasis was greater than that of peplomycin aqueous solution. Clinical trials were carried out in 7 patients with esophageal cancer who did not undergo surgery. The local response rate was 85% and the survival time was 9.4 months in average including 5 survivors.