Abstract

PSC 833 (valspadar) is a non-immunosuppressive and non-nephrotoxic cyclosporin analogue which is a potent inhibitor of the multidrug resistance transporter, P-glycoprotein. This protocol is of interest because of the activity of paclitaxel and doxorubicin in breast, ovarian and lung cancers. In this Phase I study, we are assessing the effect of PSC 833 on the pharmacokinetics and pharmacodynamics of doxorubicin and paclitaxel, with the goal of defining: a) a maximally tolerated dose (MTD) of doxorubicin with paclitaxel; b) maximally tolerated doses for doxorubicin and paclitaxel in conjunction with PSC 833; and c) the maximally tolerated doses of doxorubicin, paclitaxel, and PSC, utilizing G-CSF support. Patients initially receive doxorubicin and paclitaxel and are being enrolled in cohorts of three to ten patients per cohort. Detailed pharmacokinetics for doxorubicin, doxorubicinol, and paclitaxel are being performed. We anticipate that PSC 833 will significantly increase the area under the curve and the half-life of both doxorubicin and paclitaxel. This study is ongoing and should be completed during the current grant year.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000070-35A1
Application #
6246167
Study Section
Project Start
1997-05-15
Project End
1997-11-30
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
35
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Evangelou, Evangelos (see original citation for additional authors) (2018) Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat Genet 50:1412-1425
Doherty, Aiden; Smith-Byrne, Karl; Ferreira, Teresa et al. (2018) GWAS identifies 14 loci for device-measured physical activity and sleep duration. Nat Commun 9:5257
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
Frayling, Timothy M; Beaumont, Robin N; Jones, Samuel E et al. (2018) A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure. Cell Rep 23:327-336
Latva-Rasku, Aino; Honka, Miikka-Juhani; Stan?áková, Alena et al. (2018) A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes 67:334-342
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
Holmes, Michael V; Pulit, Sara L; Lindgren, Cecilia M (2017) Genetic and epigenetic studies of adiposity and cardiometabolic disease. Genome Med 9:82
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628

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