Mitomycin C (MMC) was microencapsulated with ethylcellulose. The microcapsules contained, on average, 80% of biologically active MMC and had a sustained-release property. The mean particle size was 224 p m so that the microcapsules were readily infused into a canine kidney through arterial catheterization. Ex vivo infusion demonstrated that the microcapsules lodged in the small arteries, mainly at the cortico-medullary junction, and released concentrated MMC into the surrounding tissue. In vivo experiments revealed that the canine kidneys infused with the microcapsules retained active MMC for more than 6 hours and showed extensive necrosis five days after the infusion. The kidneys infused with nonencapsulated MMC rapidly excreted MMC and showed mild histologic changes. The blood level of MMC released from the intrarenal microcapsules was markedly reduced as compared with control levels. The results suggest that the potential therapeutic effect of intraarterial infusion of MMC microcapsules is a function of embolization and prolonged drug action, and that selective infusion of MMC microcapsules into tumor-supplying arteries could facilitate intensive topical chemo-therapy with minimum systemic side-effects.
In vitro sensitivity of an established cell line from human urinary bladder cancer to various chemotherapeutic agents was determined by 14C-leucine incorporation into the target cells. Of 12 drugs tested, Carboquone, Neocarzinostatin, Actinomycin D, Adriamycin, Mitomycin C and Chromomycin A3 produced intensive cytotoxic effects, while Thio-Tepa, Bleomycin, 5-Fluorouracil and Vincirstine were less cytotoxic, Intravesical instillation of Carboquone, one of the most toxic agents in vitro, resulted in complete or partial tumor remission in 6 of 9 patients with bladder cancer. Prophylactic effects of periodic intravesical Carboquone were also indicated in 7 of 8 patients who had experienced recurring superficial bladder tumors.
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