|
|
 Previous Article | Table of Contents | Next Article 
In vivo cell growth and pharmacologic determinants of clinical response in
acute myelogenous leukemia
JE Karp, RC Donehower, JP Enterline, GB Dole, MG Fox and PJ Burke
Cell Proliferation and Pharmacology Laboratories, Johns Hopkins Oncology
Center, Baltimore, MD 21205.
A predictable increase in the proliferative rate of malignant cells
remaining after initial cytoreduction in vivo forms the rationale for timed
sequential therapy (TST) with 1-B-D-arabinofuranosylcytosine (ara- C) for
adult acute myelogenous leukemia (AML). The relationship between in vivo
leukemic cell growth, intracellular ara-C metabolism, and clinical response
to ara-C-containing TST was evaluated by comparing AML marrow cell growth
kinetic and biochemical pharmacologic determinants obtained before therapy
(day 0) and at the predicted peak of in vivo postdrug residual tumor
proliferation (day 8). Serial measurements of DNA synthesis and net
intracellular ara-C metabolism demonstrated marked increases in both
determinants in day 8 residual tumor when compared with the pretreatment
cells for newly diagnosed adults achieving complete remission but not for
TST-refractory patients. The interrelationship of AML cell proliferation
and biochemical pharmacology together quantitate cytotoxicity measured by
both achievement and duration of remission and serve to predict eventual
clinical outcome in response to TST with ara-C where both growth and
favorable pharmacokinetics are intrinsic to the success of the drug
schedule.
Volume 73,
Issue 1,
pp. 24-30,
01/01/1989
Copyright © 1989 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. E. Karp, A. Passaniti, I. Gojo, S. Kaufmann, K. Bible, T. S. Garimella, J. Greer, J. Briel, B. D. Smith, S. D. Gore, et al.
Phase I and Pharmacokinetic Study of Flavopiridol followed by 1-{beta}-D-Arabinofuranosylcytosine and Mitoxantrone in Relapsed and Refractory Adult Acute Leukemias
Clin. Cancer Res.,
December 1, 2005;
11(23):
8403 - 8412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Mesa, D. Loegering, H. L. Powell, K. Flatten, S. J. H. Arlander, N. T. Dai, M. P. Heldebrant, B. T. Vroman, B. D. Smith, J. E. Karp, et al.
Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine
Blood,
July 1, 2005;
106(1):
318 - 327.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Castaigne, S. Chevret, E. Archimbaud, P. Fenaux, D. Bordessoule, H. Tilly, T. de Revel, M. Simon, B. Dupriez, M. Renoux, et al.
Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study
Blood,
October 15, 2004;
104(8):
2467 - 2474.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Karp, I. Gojo, R. Pili, C. D. Gocke, J. Greer, C. Guo, D. Qian, L. Morris, M. Tidwell, H. Chen, et al.
Targeting Vascular Endothelial Growth Factor for Relapsed and Refractory Adult Acute Myelogenous Leukemias: Therapy with Sequential 1-{beta}-D-Arabinofuranosylcytosine, Mitoxantrone, and Bevacizumab
Clin. Cancer Res.,
June 1, 2004;
10(11):
3577 - 3585.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Karp, D. D. Ross, W. Yang, M. L. Tidwell, Y. Wei, J. Greer, D. L. Mann, T. Nakanishi, J. J. Wright, and A. D. Colevas
Timed Sequential Therapy of Acute Leukemia with Flavopiridol: In Vitro Model for a Phase I Clinical Trial
Clin. Cancer Res.,
January 1, 2003;
9(1):
307 - 315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
