Phase i trial of 7-hydroxystaurosporine and fludararbine phosphate: In vivo evidence of 7-hydroxystaurosporine induced apoptosis in chronic lymphocytic leukemia

Gerald E. Marti, Maryalice Stetler-Stevenson, Nicole Drbohlav Grant, Therese White, William D. Figg, Tanyifor Tohnya, Elaine S. Jaffe, Kieron Dunleavy, John E. Janik, Seth M. Steinberg, Wyndham H. Wilson

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

This is a phase I study of 7-hydroxystaurosporine (UCN-01) and fludararbine monophosphate (FAMP) in relapsed lymphoma. UCN-01 alone was administered in cycle 1 and with FAMP in cycles 26. FAMP was escalated in cohorts from 1 to 5 days. UCN-01 and FAMP pharmacokinetics and apoptosis of malignant lymphocytes was evaluated. Eighteen patients were enrolled. Standard FAMP with UCN-01 was tolerated without dose-limiting toxicity (DLT) and those seen were common to either agent alone. One patient died due to Stevens-Johnson syndrome. Seven of 18 patients responded. No pharmacological effect of UCN-01 by FAMP was noted. Lymphocytosis occurred in 15 of 18 patients following UCN-01 to paradoxically increase circulating tumor cells. UCN-01 induced apoptosis in six of eight patients with chronic lymphocytic leukemia (CLL). UCN-01 does not increase FAMP toxicity. Transient lymphocytosis followed by apoptosis occurs with UCN-01. Mobilization from tissue reservoirs may play a role in the induction of cell death in malignant lymphocytes.

Original languageEnglish (US)
Pages (from-to)2284-2292
Number of pages9
JournalLeukemia and Lymphoma
Volume52
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • CLL
  • Cell death
  • Flow cytometry
  • Protein kinase inhibitor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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