Arterial infusion therapy of SMANCS/Lipiodol(SX/LP) is a prototype DDS therapy of macromolecular drug, which has two remarkable advantages:selective delivery of the drug as pinpointed missile and slow release of drug for a long time (months). However, its arterial infusion only once is not enough for a remarkable regression of tumor, but several subsequent infusions are needed that will usually warrant remarkable outcome. In many hospitals in Japan, its usages have been unsatisfactory and the result is moderate by our standard.
We report here most advanced procedure of SX/LP infusion in detail, which becomes effective to metastatic liver cancer, cholangiocell carcinoma, and cancer of kidney, lung and other organs. Namely, arterial infusion of SX/LP is carried out under angiotensin II induced hypertensive state where normal blood vessels exhibit vasoconstriction and tighter endothelial cell/cell junction, while tumor vessels will open up passively permitting increased blood flow, thus, more drugs (SX/LP) delivery in tumor tissue become possible. On the contrary to delivery to tumor, less drug is delivered to normal tissues as the vascular cell/cell junction is tighter. This method is called SMANCS dynamic therapy and it is now applied not only for hepatocellular carcinoma, but many other tumor as described above even at advanced stage. The method was shown very safe and resulted in remarkable responses with excellent QOL and least toxic.

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Anticancer agents are rapidly absorbed into the circulation when given intraperitoneally in a form of aqueous solution. Therefore, it is difficult to maintain the drug concentration at a high level for a long time in peritoneal cavity. To overcome the difficulty, a lot of modification and improvement using DDS(drug delivery system) have been done. Additionally, recent investigation has revealed the mechanism of peritoneal metastasis and the drug distribution after administrated intraperitoneally. Based on the evidences, this article reviews DDS for intraperitoneal chemotherapy including recent advances.

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Both intravesical chemotherapy using anti-cancer drug and immunotherapy are standard treatment for superficial bladder tumor. The latter, intravesical immunotherapy using bacillus Calmette-Guerin(BCG), is the most clinically used cancer immunotherapy with established efficacy. The most common indication of intravesical treatment is prevention of recurrence after transurethral resection(TUR) of superficial bladder tumor. The intravesical therapy is also known to be effective in eradicating carcinoma in situ. The goal of the treatment is to prevent progression to invasive bladder cancer.
Single, early instillation of anti-cancer drug after TUR is indicated in low and intermediate risk superficial bladder tumors. The treatment has proven effective but the role of maintenance chemotherapy has been controversial. Intravesical BCG therapy generally have proven more efficacious than chemotherapy, but its side-effects are more pronounced. Several meta-analyses showed that intravesical BCG therapy significantly reduce the risk of disease progression. In this review, we discuss the current status and recent investigation including meta-analysis of the intravesical treatment for superficial bladder.

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Hepatic arterial infusion chemotherapy(HAI) has often been selected as a therapeutic option for patients with far-advanced hepatocellular carcinoma(HCC), either unresectable or difficult to treat with local therapy. However, the survival benefits with this therapy have not yet been unequivocally proved so far. No standard regimen has been established despite developing drug delivery devices or chemotherapeutic regimens. Recently, several regimens of HAI with interferon have shown the tumor response and survival benefit, and such a combination therapy would be a new promising therapeutic strategy of advanced HCC. We emphasize that HAI should be performed on the basis of appropriate skills, with knowledge of pharmacokinetics.

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Administrating DSM through hepatic artery causes blood stasis for about one hour. DSM induces drug uptake in the tumor area, and moreover, DSM increases tumor-to-normal drug concentration ratio in the liver. Because of these characteristics, DSM has gotten the insurance adaptation for the local treatment of metastatic liver cancer in Japan.
We have treated various hepatic malignancies with transcatheter arterial chemoembolization using DSM(DSM-TACE). Response rate for liver metastasis of gastric cancer, liver metastasis of neuroendocrine carcinoma and liver metastasis and inoperable intrahepatic cholangiocarcinoma were 62.5%, 70.0% and 52.9%, respectively. Median survival times(MSTs) were 36.1 months, 28.4 months and 15.4 months, respectively. And MSTs of inoperable stage IV HCC was 23.0 months for responder and 5.8 months for non-responder, respectively. There was no liver injury related death.
In conclusion, DSM-TACE was found to be a relatively safe and effective treatment for inoperable hepatic malignancies.

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The study aimed to devise a novel anticancer drug delivery system with targeting and a sustained release of the agent.
We used two different types of 70% deacetylated chitin as the drug carriers:namely, DAC-70 and DAC-70'. Cis-platinum(CDDP) and fluorouracil(5-FU) were applied as the model drugs. Targeting effect was evaluated by ex vivo adhesive force between each system and human colonic mucosa. Release profile of the anticancer drugs was examined in vitro. Each system prepared demonstrated a stronger visco-elasiticity comparing with that of the conventional drugs. Seventy percent of CDDP was gradually delivered from the DAC-70/ CDDP for 3 days, while the release from the DAC-70'/ CDDP was significantly slower. The DAC/ 5-FUs exhibited an initial bursting of the 5-FU.
We presume that the differences observed in the drug release were closely related with both the degradability of the carriers and interactions between each drug and vehicle. The studies suggested that the DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.

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DDS therapeutic system of next generation is a novel technology and methodology applicable for deep-site diseases. This system is built up by combining the conventional DDS technologies with external physical energies. It is expected that this combination enables the conventional DDS to enhance the therapeutic effects. In this communication, a new therapeutic system of next generation with magnet-inductive DDS is introduced, briefly explaining the technical factors necessary to realize the new DDS therapy.

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