NK 611 is a new semisynthetic analogue of
etoposide, which presumably also acts through inhibition of
topoisomerase II, and has been found to be more potent against several
cancer cell lines in vitro than
etoposide. 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 1 h in 45 evaluable tumour specimens,
NK 611 showed clear concentration-dependent antitumour activity. At 51 microM, 49% of specimens were markedly inhibited. Using a long-term (21-28 day) exposure at 6.8 microM, 58% of 50 evaluable specimens were profoundly inhibited. At equimolar concentrations,
NK 611 was as active as
etoposide. Across all tumour types studied,
NK 611 was as active as
vinblastine,
bleomycin,
doxorubicin,
5-fluorouracil,
mitomycin-C and
cisplatin. Our results showed cross resistance to
etoposide in the majority of specimens. Activity of
NK 611 was greater with long-term exposure than with short-term exposure indicating schedule dependency. We conclude that
NK 611 has a wide spectrum of in vitro antitumour activity. Since preliminary clinical information suggests that this
drug is well tolerated at high doses, further development of this agent in Phase II trials with multiple dosing schedules is warranted.