N4-octadecyl-1-beta-D-arabinofuranosylcytosine (
NOAC) is a new lipophilic derivative of 1-beta-D-arabinofuranosylcytosine (
ara-C) with potent antitumor activity against
leukemias and solid
tumors. In this study the activity of
NOAC against freshly explanted clonogenic cells from human
tumors was determined and compared with conventional
antitumor agents.
NOAC was used in two liposomal preparations, a stable lyophilized and a freshly prepared liquid formulation. Both formulations inhibited
tumor colony formation equally in a concentration-dependent fashion in both short- (1 h) and long-term (21-28 d) exposure experiments.
NOAC (100 microM, long-term exposure) had a significantly better activity compared to the clinically used drugs
cisplatin,
doxorubicin,
5-fluorouracil,
gemcitabine,
mitomycin C and
etoposide. The comparison of
NOAC with
ara-C in the long-term exposure experiment showed that
ara-C was more effective at 4 and 10 microM, whereas at 1 and 100 microM there was no difference between the two drugs.
NOAC was less toxic in a hematopoietic stem cell assay than
ara-C and
doxorubicin by factors ranging from 2.5 to 200, indicating that this
drug is well tolerated at high doses. The antitumor activity of
NOAC (
NSC 685096) was confirmed by the NCI in vitro
drug screening program where the
drug was found to be active against several types of human
tumors. Further development of
NOAC in phase II studies is warranted.