The therapeutic efficacy of
PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met-ethoxy HCl, was evaluated using the transplantable
L1210 leukemia and Ridgway
osteogenic sarcoma tumor lines and the spontaneous C3H/StRos mammary
tumor and AKR
leukemia tumor models. Given in a single i.p. dose at 5-10 mg/kg on day 2 or in two
injections of 5-7 mg each on days 2 and 9 to BDf1 mice with peritoneal
L1210 leukemia grafts,
PTT.119 increased the life spans (ILS) of the population dying of
tumor by 94%-313%. In addition, 10% of the mice receiving 7 mg
PTT.119 on days 2 and 9 were free of L1210 leukemic grafts when autopsied at the end of the 70-day observation period. The average life span of AKR mice with Ridgway
osteogenic sarcoma grafts was significantly increased from 36-40 days to greater than 79 days following one or two s.c.
injections of 5, 7, or 12.5 mg/kg
PTT.119. Administration of
PTT.119 at 14 or 14 and 21 days after
tumor graft not only induced regression of palpable
tumors but resulted in the absence of grafts in 60%-70% of the mice in several of the treated groups on autopsy at 180 days. In contrast, spontaneous mammary
tumors were less susceptible to
PTT.119; an ILS of only 15%-38% was observed in C3H/StRos mice, which eventually succumbed to
tumor. Nevertheless, the total regression of initial
tumors and the absence of further
tumor incidence (greater than 180 days) was confirmed by autopsy in 5%-10% of the C3H/StRos mice receiving multiple i.p.
injections of 5 or 7.5 mg/kg
PTT.119. The
drug was highly effective against spontaneous AKR
leukemia; multiple s.c. or i.p.
injections for a total of 15-40 mg/kg
PTT.119 increased the average 25-day life span up to 723% and sustained remission in 9%-40% of the animals for greater than 6 months.