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In vitro activity of liposomal N4octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC), a new lipophilic derivative of 1-beta-D-arabinofuranocylcytosine on biopsized clonogenic human tumor cells and hematopoietic precursor cells


Schwendener, R; Friedl, K; Depenbrock, H; Schott, H; Hanauske, A R (2001). In vitro activity of liposomal N4octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC), a new lipophilic derivative of 1-beta-D-arabinofuranocylcytosine on biopsized clonogenic human tumor cells and hematopoietic precursor cells. Investigational New Drugs, 19(3):203-210.

Abstract

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.

Abstract

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2001
Deposited On:27 Mar 2009 08:35
Last Modified:05 Apr 2016 13:11
Publisher:Springer
ISSN:0167-6997
Publisher DOI:https://doi.org/10.1023/A:1010679411001
PubMed ID:11561676

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