Reference

Effects on human peripheral lymphocytes of in vivo administration of 9-b-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887), a new purine antimetabolite

Effects on human peripheral lymphocytes of in vivo administration of 9-b-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887), a new purine antimetabolite. Boldt, David H.; Von Hoff, Daniel D.; Kuhn, John G.; Hersh, Marla (Health Sci. Cent., Univ. Texas, San Antonio, TX 78284, USA). Cancer Res., 44(10), 4661-6 (English) 1984. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) 9-b-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887)(2-F-ara-AMP) [75607-67-9] is a new purine antimetabolite with documented preclin. activity against a no. of animal tumors. Data from in vitro studies and preclin. animal toxicol. trials indicated that 2-F-ara-AMP might be lymphocytotoxic. The effects of 2-F-ara-AMP on peripheral lymphocytes of patients receiving 13 courses of the drug by i.v. bolus daily for 5 days were studied. Lymphocytopenia developed rapidly (median time to nadir, 6 days) and was reversible. Total T-lymphocyte counts fell during treatment, with calcd. mean abs. T-cell counts decreasing by 90%. Decreases were obsd. in all major T-lymphocyte subsets. By contrast, calcd. B-lymphocyte counts decreased an av. of 50% and were noted to increase during two treatment cycles. In vitro recoveries of cells from each major lymphocyte subpopulation were compared before and after administration of 2-F-ara-AMP. Recoveries of total mononuclear cells, total T-cells, and non-T-, non-B-cells all were reduced substantially by 2-F-ara-AMP, but B-cell recovery was not reduced. These in vivo data, the first in human subjects, are in agreement with in vitro studies of halopurine nucleotide analogs which have demonstrated that T-cells are more sensitive than are B-cells to the cytotoxic effects of these compds.

Responses of human bone marrow progenitor cells to fluoro-ara-AMP, homoharringtonine, and elliptinium

Responses of human bone marrow progenitor cells to fluoro-ara-AMP, homoharringtonine, and elliptinium. Umbach, Gunter E.; Hug, Verena; Spitzer, Gary; Thames, Howard; Drewinko, Benjamin (M. D. Anderson Hosp. and Tumor Inst., Univ. Texas, Houston, TX, USA). Invest. New Drugs, 2(3), 263-5 (English) 1984. CODEN: INNDDK. ISSN: 0167-6997. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The cytotoxicity of the investigational anticancer drugs fluoro-ara-AMP [75607-67-9], homoharringtonine [26833-87-4], and elliptinium [58337-35-2] on normal human granulocyte-macrophage colony-forming units in culture (GM-CFU) was investigated using a bilayer soft agar system. For each drug, the dose-dependent survival curve on a semilogarithmic plot formed a straight line. The drug concns. capable of killing 63% of GM-CFU (D0) were : 0.51 mg/mL (fluoro-ara-AMP), 0.004 mg/mL (homoharringtonine) and 0.026 mg/mL (elliptinium). The in vitro toxicity of drugs on bone marrow progenitor cells did not correlate with the relative myelosuppressive potency obsd. in vivo.