Abstract

Early phase evaluation of anticancer drugs has traditionally used toxicity (usually hematological) rather than efficacy end points to establish appropriate dosing schedules. To establish a biochemical efficacy end point for overcoming alkylguanine DNA alkyltransferase (AGT)-mediated tumor cell resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, we performed a novel dose escalation clinical trial for the AGT-depleting agent 06-benzylguanine (BG). The dose of BG required to deplete AGT to undetectable levels (BMD(T) in sequential computed tomography-guided tumor tissue biopsies before BG and 18 h after BG was determined. Thirty patients received doses of BG ranging from 10 to 120 mg/m2 on the GCRC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000080-38
Application #
6305441
Study Section
Project Start
1999-12-01
Project End
2000-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
2000
Total Cost
$19,199
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie et al. (2018) Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis. J Perinat Med 46:926-933
Clark, Erin A S; Weiner, Steven J; Rouse, Dwight J et al. (2018) Genetic Variation, Magnesium Sulfate Exposure, and Adverse Neurodevelopmental Outcomes Following Preterm Birth. Am J Perinatol 35:1012-1022
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Saade, G R; Thom, E A; Grobman, W A et al. (2018) Cervical funneling or intra-amniotic debris and preterm birth in nulliparous women with midtrimester cervical length less than 30 mm. Ultrasound Obstet Gynecol 52:757-762
Inker, Lesley A; Grams, Morgan E; Levey, Andrew S et al. (2018) Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. Am J Kidney Dis :
Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671
Juraschek, Stephen P; Appel, Lawrence J; Miller 3rd, Edgar R (2017) Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension. Am J Hypertens 30:871-875
O'Toole, John F; Bruggeman, Leslie A; Madhavan, Sethu et al. (2017) The Cell Biology of APOL1. Semin Nephrol 37:538-545
Chen, Teresa K; Tin, Adrienne; Peralta, Carmen A et al. (2017) APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD. Clin J Am Soc Nephrol 12:1771-1777
Catalano, Patrick M; Shankar, Kartik (2017) Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child. BMJ 356:j1

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