In vitro activity of liposomal N(4)octadecyl-1-beta-D-arabinofurano-sylcytosine (NOAC), a new lipophilic derivative of 1-beta-D-arabino-furanocylcytosine on biopsized clonogenic human tumor cells and hematopoietic precursor cells

N-4-octadecyl-1-beta -D-arabinofuranosylcytosine (NOAC) is a new lipophilic derivative of 1-beta -D-arabinofuranosylcytosine (ara-C) with potent antit umor activity against leukemias and solid tumors. In this study the activit y of NOAC against freshly explanted clonogenic cells from human tumors was determined and compared with conventional antitumor agents. NOAC was used i n two liposomal preparations, a stable lyophilized and a freshly prepared l iquid formulation. Both formulations inhibited tumor colony formation equal ly in a concentration-dependent fashion in both short- (1h) and long-term ( 21-28 d) exposure experiments. NOAC (100 muM, long-term exposure) had a sig nificantly better activity compared to the clinically used drugs cisplatin, doxorubicin, 5-fluorouracil, gemcitabine, mitomycin C and etoposide. The c omparison of NOAC with ara-C in the long-term exposure experiment showed th at ara-C was more effective at 4 and 10 muM, whereas at 1 and 100 muM there was no difference between the two drugs. NOAC was less toxic in a hematopo ietic 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 an titumor activity of NOAC (NSC 685096) was confirmed by the NCI in vitro dru g screening program where the drug was found to be active against several t ypes of human tumors. Further development of NOAC in phase II studies is wa rranted.