Lipo-PGE₁ was introduced onto the Japanese market in 1988 and since then it has been widely used in clinical practice. Today, the preparation became applicable clinically also in Korea and China. PGE₁ itself is relatively unstable, and amount of PGE₁ will be released from LM. Therefore, we recently produced a new lipo-PGE₁, in which a chemically stable PGE₁ prodrug (AS013) was incorporated into LM. The new lipo-PGE₁ showed an enhanced pharmacological activity, and was stable even at room temperature for 3 years. Now in USA its clinical study is ongoing.

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Leuprorelin (leuprolide) acetate, a highly active agonist of luteinizing hormone-releasing hormone (LH-RH) has been widely accepted as a representative agent utilizing drug delivery system. A single injection of this one-month or three-month depot provides persistent drug release, which has been applied to therapy in patients with prostate cancer, breast cancer, endometriosis, myoma uteri, and central precocious puberty. The profile of this drug from basic research to clinical application was reviewed.

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Recent advances in SMANCS/Lipiodol therapy for hepatic and other abdominal cancers are discussed. Two clinical procedural progresses described herein are arterial infusion of SMANCS/Lipiodol under angiotensin II induced hypertension (eg. 120 → 180 mmHg), which is followed by, or commitant infusion of SMANCS/Lipiodol and nitro-agent (nitroisosorbitol : nitrol^®) i. a. via the catheter inserted at the femoral artery (Seldinger's method). SMANCS/Lipiodol is selectively deposited much higher extent by virtue of EPR-effect and this amount was increased 2∼4 fold under hypertensive condition followed by opening up the normal blood vessels by Nitrol^® : This procedure also reduced side effect clinically to a great extent such as liver toxicity. X-ray CAT scan revealed much thickened uptake of SMANCS/Lipiodol in case of the metastatic liver cancer, cholangiocarcinoma, and pancreatic cancer, as well as hepatocellular carcinoma. For highly enhanced tumor selective delivery of SNIANCS/Lipiodol given i. a., the method using two vascular mediators (hypertension/systemic : vasodilatation/local) is more desirable than simple i. a. infusion, which resulted far better drug deposition and response, as well as QOL of the patients, than original SMANCS therapy under normotensive state.

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Current opinions in cancer pain treatment with opioid analgesics are presented in this review. Advantages of control released opioids analgesics compared with usual types are stressed. New form of opioid-a patch, recently registered in Japan, is described. After brief review of pharmacodynamics and pharmacokinetics of CR opioid, authors experiences in cancer pain treatment with this analgesic are described. The newly developed controlled-release opioid is safe and effective and may be useful.

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Long-term survival in patients with gastrointestinal stromal tumors (GISTs) was very rare. Recently treatment with imatinib mesylate, a molecular targeted agent that inhibits the KIT tyrosine kinase receptor showed 81.6% of outstanding clinical response (PR 53.7%, SD 27.9%). Grade 3 or higher toxicities occurred in 21.1% including edema, neutropenia, nausea, dermatitis, hepatitis and gastrointestinal hemorrhage. The drug was ralatively safe overall. Number of molecular targeted agents are now in clinical trial. They will be mainstay of future therapies of gastrointestinal tumors.

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The characteristics of MILTAX^®, a poultice-type patch containing ketoprofen, are here evaluated with reference to formulation, pharmacological and clinical aspects. Included is a comparison of skin permeation of ketoprofen with that of indometacin and piroxicam. The flux of ketoprofen was higher than that of other two drugs, while indometacin showed high skin permeability, but low saturated solubility, and therefore relatively poor skin permeation, L-menthol was found to be useful not only for enhancement of skin permeation, but also for giving a cool feeling to the skin. Atomic force microscopic (AFM) observations here revealed the existence of micro-domains sized a few nanometer in diameter on the surfaces of hydrophilic gels like MILTAX^®. Moreover, ketoprofen might exist as micelles surrounded by polyoxyethylene sorbitan trioleate (PST) which could play an important role in both skin permeation and maintaining drug stability. The adhesion characteristics, probe tack, sticking strength and cohesion strength, were weaker with the poultice-type patch, MILTAX^®, than with KP-T. In generally, the permeation of drugs is lower with human than with animal skin. Similarly, the flux of ketoprofen from MILTAX^® for rat skin was 2∼3 times higher than with human skin. The release of ketoprofen from the patch was approximately 60∼70% at 24hour, with a relative bioavailability (BA) of 80∼90% in comparison with oral administration. The muscle concentration of ketoprofen after MILTAX^® application was twice that after oral administration. No severe toxicity was seen in the primary and 7-day cumulative skin irritation tests in rabbits. Clinically, MILTAX^® shows comparable anti-inflammatory and analgestic efficacy to oral administration of ketoprofen, but with much reduced side effects.

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