ACTIVITY OF NK-611, A NEW EPIPODOPHYLLOTOXIN DERIVATIVE, AGAINST COLONY-FORMING-UNITS FROM FRESHLY EXPLANTED HUMAN TUMORS IN-VITRO

NK 611 is a new semisynthetic analogue of etoposide, which presumably also acts through inhibition of topoisomerase II, and has been found t o be more potent against several cancer cell lines in vitro than etopo side. The objectives of our study were to determine the activity of NK 611 against freshly explanted clonogenic cells from human tumours and compare this agent with etoposide and other clinically useful agents. After exposure for Ih in 45 evaluable tumour specimens, NK 611 showed clear concentration-dependent antitumour activity. At 51 mu M, 49% of specimens were markedly inhibited. Using a long-term (21-28 day) expo sure at 6.8 mu M, 58% of 50 evaluable specimens were profoundly inhibi ted. At equimolar concentrations, NK 611 was as active as etoposide. A cross all tumour types studied, NK 611 was as active as vinblastine, b leomycin, doxorubicin, 5-fluorouracil, mitomycin-C and cisplatin. Our results showed cross resistance to etoposide in the majority of specim ens. Activity of NK 611 was greater with long-term exposure than with short-term exposure indicating schedule dependency. We conclude that N K 611 has a wide spectrum of in vitro antitumour activity. Since preli minary clinical information suggests that this drug is well tolerated at high doses, further development of this agent in Phase II trials wi th multiple dosing schedules is warranted.