Abstract
Historical aspects of antibiotic and anticancer drug development were briefly reviewed. Based on the authors experience with highly tumor targeting anticancer agents especially SMANCS, several proposals are made to change old paradigm to new paradigm in cancer chemotherapy. Firstly, the dose setting based on maximum tolerable dose to that based on tumor size or tumor volume. When tumor takes up anticancer agents (usually polymeric drug) 10 times or more of the concentration in blood, then tumor with a weight of 1 kg will be equivalent to 10 kg volume (10 L) equivalent, which will be 2 fold larger than blood volume (of body weight of 65 kg). The dose of drug such as SMANGS/Lipiodol should be most reasonably calculated based on the tumor weight, i. e., tumor of 300 g should be given at least 10 times of tumor of 3 g, and perhaps administered more frequently in the larger tumor. Secondly, present criteria of efficacy (or response) for so called “no effect” include no tumor growth (no change) or to tumor size regression less than 50% reduction of the original size. If the drug is not toxic and beneficial to a patient, especially in view of QOL, such marginal or no reduction, if not progressive tumor growth, should be counted as a favorable effect. Prolonged period of no change, e.g. 3 months, should be counted as effective. Thirdly, other beneficial effect for patients such as suppression of ascitic or pleural fluid accumulation, suppression of metastasis, or recurrent rate should be counted beneficial. QOL of the patients should be evaluated more seriously. For instance, any prolongation of survival period of a patient, who is free of bed-confinement, should be taken into the account.
