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A Phase 1 study of UCN-01 in combination with irinotecan in patients with resistant solid tumor malignancies

Published on Jun 1, 2011in Cancer Chemotherapy and Pharmacology3.008
· DOI :10.1007/s00280-010-1410-1
Paula M. Fracasso25
Estimated H-index: 25
(UVA: University of Virginia),
Kerry J. Williams3
Estimated H-index: 3
(WashU: Washington University in St. Louis)
+ 23 AuthorsHelen Piwnica-Worms67
Estimated H-index: 67
(WashU: Washington University in St. Louis)
Abstract
Purpose UCN-01 (7-hydroxystaurosporine) is a multi-targeted protein kinase inhibitor that exhibits synergistic activity with DNA-damaging agents in preclinical studies. We conducted a Phase I study to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic, and pharmacodynamic effects of UCN-01 and irinotecan in patients with resistant solid tumors.
  • References (69)
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Purpose 7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor that inhibits several serine–threonine kinases including PKC and PDK1. Due to the preclinical synergistic effects seen with topoisomerase I inhibitors and non-overlapping toxicity, UCN-01 and irinotecan were combined in a dose-finding study designed to determine the maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of UCN-01 and irinotecan.
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