[Phase I study of forphenicinol, a new biological response modifier]

Forphenicinol, [L-(4-hydroxymethyl-3-hydroxyphenyl) glycine], a new biological response modifier, is a derivative of forphenicine, an inhibitor of chick intestine alkaline phosphatase, discovered by H. Umezawa from the microbial culture filtrate. In order to find an optimal dose schedule of forphenicinol, the drug was given p.o. at doses ranged from 10, 50, 100, 400 to 800 mg once a day for 7 days to 103 patients (39 malignant and 64 benign). No side effect was observed. Statistical analysis was performed on immunological parameters, including WBC; lymphocyte, T-cell, B-cell, T gamma-cell (each % and count); S.I. of PHA and Con A, NK cell activity and K cell activity before and after administration. The patients were divided into the "low-dose" group given less than 100 mg/day of the drug and the "high-dose" group given more than 400 mg/day. Further, on the basis of values of each parameter before administration, the patients were divided into the "low-before" or the "high-before" group, when the pretreated value of parameters was lower or higher than the median of all cases. In the malignant patients, lymphocyte (% and count), T-cell (% and count) and B-cell (% and count) significantly increased in the "low-dose"-"low-before" group (p less than 0.05), but B-cell (%) and S.I. of PHP and Con A decreased in the "low-dose"-"high-before" group. On the contrary, there was no significant change in both the "low-before" and the "high-before" group, when "high-dose" of the drug was given. In the benign patients T gamma-cell (% and count) and NK cell activity were found to be significantly increased in the "high-dose"-"low-before" group, indicating some difference in response of parameter from cancer patients. An optimal dose of forphenicinol for cancer patients was considered to be in a range of 10-100 mg/day.