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Based on the overall results of a UFT phase II study made in 104 institutions in Japan from April of 1979 to September of 1980, there was a response rate of 27.7% with 3 CR cases and 49 PR cases out of 188 stomach cancer cases considered as evaluable according to solid cancer chemotherapy direct efficacy criteria. Other response rates were spleen cancer 25%, gallbladder cancer 25%, liver cancer 19.2%, colorectal cancer 25%, breast cancer 32% and lung cancer 7%. Side effects out of 551 cases were, loss of appetite 24.3%, nausea/vomiting 12.5%, diarrhea 11.1% and other digestive system symptoms mainly. The hematologic side effects were mild, being 6.9%. According to the UFT phase II study, in 438 evaluable cases followed for 5 years after testing, the results were analyzed in terms of therapeutic efficacy and survival time. In 185 stomach cancer cases, 50% survival time was 185 days, with CR + PR cases 336 days, MR + NC cases 183 days, and PD cases 97 days. Colorectal cancer showed a 50% survival time of 227 days in 54 cases, while that for 49 breast cancer cases was 505 days. Total Ftorafur (FT) results using the same criteria from the UFT phase II study revealed, from a comparison of dosage and disease type, that UFT did not enhance FT side effects; rather, it markedly increases effectiveness. Therefore, on the basis of its response rate and the survival time for the cases of digestive system cancer, UFT is considered an effective anticancer agent.

A phase II study of new anthracycline, THP, was conducted in 46 patients with hematological malignancies in a cooperative study. THP was given intravenously either at a dose of 13-34 mg/m2 for 3-5 consecutive days or 35-50 mg/m2 at 3-4 week intervals. Of 21 patients with acute leukemia, complete response (CR) was observed in 3 patients and partial response (PR) in 4. Of 22 patients with malignant lymphoma, CR was observed in 2 and PR in 6. The predominant toxicity was myelosuppression. Leukopenia was noted in 73% of patients and thrombocytopenia in 14%. Anorexia, nausea and vomiting were observed in 49%, 26% and 23%, respectively. Alopecia and acute cardiac toxicities were mild and recovered quickly on discontinuation of THP. Thus, THP was found to be effective for acute leukemia and malignant lymphoma.

A phase I study ofN 4-behenoyl-1-β-d-arabinofuranosylcytosine (BHAC) was conducted in 66 patients, 41 with solid tumors and 25 with hematological malignancies. The patients received either a 2-h single intravenous (i.v.) drip infusion (Schedule 1) or consecutive daily 2-h i.v. infusions (Schedule 2). In Schedule 1 the daily dose was initiated with 1.5 mg kg−1 which was escalated up to 7 mg kg−1. Side-effects were mild, and included nausea, vomiting, epilation, and hot flushes. Because of the presence of the solvent vehicle, HCO-60 and in consideration of the mechanism of action of BHAC, the dose escalation was stopped at 7 mg kg−1. In Schedule 2, the daily dose was started with 1.5 mg kg−1 which was escalated up to 8 mg kg−1 and given for 2–16 days. Myelosuppression was found to be dose-limiting toxicity. The maximum tolerated dose (MTD) in patients with non-hematological solid tumors was assumed to be 5 mg kg−1 daily × 5 days. The plasma disappearance curve of BHAC looked biphasic, and when 4 mg kg−1 of BHAC were administered the half-lives of the initial phase (t 1/2α) and the second phase (t 1/2β) were calculated as 0.798 and 5.76 h respectively. In Schedule 2 complete remission was observed in 5 out of 21 patients with acute leukemia, one partial remission in Hodgkin’s disease, and one 1-B response (Karnofsky) in thyroid papillary adenocarcinoma.

Twenty patients with malignant abdominal tumors were evaluated by compound contact B-mode ultrasonic scanning. The studies were carried out during and after antineoplastic treatment with chemotherapy, radiation or surgery. Gain and sensitivity settings were kept constant before and after treatment. The changes in echographic findings were correlated with clinical, laboratory and/or autopsy findings. Ultrasound proved to be a very useful and convenient way to evaluate the antitumor effect of various chemotherapeutic agents. Typical echograms are shown to illustrate the method of ultrasonic evaluation.

A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was found to be useful for the treatment of chronic myelogenous leukemia (CML) in the chronic phase. To compare the efficacy of MCNU with that of busulfan, patients were randomized. In the 40 patients administered MCNU, the median time to the achievement of a complete remission (CR) was 50 days. This value was shorter than that observed in 37 patients administered busulfan (126 days, p less than 0.05). There were no differences in the rate of CR achieved, mortality, median time to the onset of blast crisis (BC), BC rate, or survival rate during the observation period. The overall incidence of side effects was higher for MCNU (31%) than for busulfan (15%), but the symptoms were mild, transient and tolerable for most patients. These results suggest that MCNU is a safe and valuable addition to the therapeutic repertoire for the control of CML.

A noninvasive method is presented for the measurement of the digital arterial compliance (C s and C d ) by use of a pneumatic cuff (Gaertner capsule) as a gasket when inflated and a fingertip pneumoplethysmograph. The compliance is obtained from the mean amplitude of the volume pulse waves \( \left( {\Delta {{\bar v}_i}{\rm{ and }}\Delta {{\bar v}_j}} \right) \) under the effect of the cuff pressures (P 0-i and P 0-j) by $$ \begin{array}{*{20}{c}} {{C_s} = {C_i} = 3\Delta {{\bar v}_i}/\left( {{P_s} - {P_{0 - i}}} \right)}\\ {{C_s} = {C_j} = \Delta {{\bar v}_j}/\left( {{P_s} - {P_{0 - j}}} \right)}\\ {{C_d} = {C_{i - j}} = 3\left( {\Delta {{\bar v}_j} - \Delta {{\bar v}_i}} \right)/\left( {{P_{0 - i}} - {P_{0 - j}}} \right)} \end{array} $$ during the dicrotic phase defined in this study. The value C s (= C d ) obtained from the data during the dicrotic phase is regarded as the compliance. As the cuff pressure is lowered to less than the systolic pressure, the coincident cuff pressure at the moment when the pulse wave begins to appear is regarded as the systolic pressure (P s ). The series of the pulse wave changes following the cuff pressure change is classified into five stages, i.e., A, B, C, D, and E. Stage D (dicrotic phase) is the successive stage after C and is characterized by the fact that the value C s is equal to the value C d and the pulse waves have the dicrotic notch. During the dicrotic phase, the venous pressure, the capillary pressure, and the diastolic pressure of arterioles in the segment distal to the compressed area approximate the cuff pressure (P 0).

We have been making comparative studies of in vivo distribution and clinical effects of many anticancer drugs. In this paper we present our experimental results and some clinical effects of adriamycin with special reference to its in vivo distribution.

The mechanism of the bigeminal rhythm induced by the toxic dose of rapid acting unique cardiac glycoside; Proscillaridin A, was investigated by means of the intracellular microelectrode technique, upon the guinea pig ventricular fibers, and the clinical case record of bigeminal rhythm induced by its intoxication was also analysed. On the experimental finding, the bigeminal rhythm appeared when the repolarization phase 2 was decreased about 40%. Clinically, the plethysmographic finding may be the good parameter to judge the appropriate dosage of Proscillaridin A for its maintenance dose for every individual patient.