117 Effects of KP 735, a new platinum-based antitumor agent on clonogenic growth of freshly explanted human tumors in vitro

Cis-Diammine[(bis(phosphonatomethy1)amino)acetato(2−)−O 1 , N 1 ] platinum (II), (KP 735) is a new platinum-based agent which has shown antitumor activity in established tumor cell lines. We have studied the effects of KP 735 on soft agar colony formation of freshly explanted human tumors in vitro . Fifty-three out of 74 specimens (72%) are evaluable. Major tumor subgroups were: breast (9), mesothelioma (7), melanoma (6), kidney (5), carcinoma of unknown primary (6). Using a continuous incubation (21–28 days), concentration-dependent inhibition (colony formation ≤ 0.5 × control) was observed with 0/53 specimens inhibited at 0.1 μg/ml, 9/53 (17%)at 1.0 μg/ml and 32/53 (60%) at 10 μg/ml. In a short-term incubation (1 hour), concentration-dependent inhibition was observed with 1/51 specimens (2%) inhibited at 0.1 μg/ml, 3/51 (6%) at 0.4 μg/ml, 6/51 (12%) at 1.0 μg/ml, 15/51 (29%) at 10 μg/ml and 30/51 (59%) at 100  μg/ml. At the highest concentration, KP 735 was more active than vinblastine (12/33 specimens (36%) inhibited, P  = 0.043 McNemar's test), cisplatin (16/51 (31%), P  = 0.001) and carboplatin (11/51 (22%), P  = 0.001). We conclude that KP 735 has antineoplastic activity against freshly explanted human tumor cells in vitro . The spectrum of activity includes tumors with known clinical resistance to conventional chemotherapy. Further clinical development of this agent thus seems warranted.