title: Phase I trial of 7-hydroxystaurosporine and fludararbine phosphate: in vivo evidence of 7-hydroxystaurosporine induced apoptosis in chronic lymphocytic leukemia.
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 2-6. 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.
authors: Laboratory of Stem Cell Biology, Cellular and Tissue Therapy Branch, Division of Cell and Gene Therapies,Office of Cellular, Tissues and Gene Therapies, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. gemarti@helix.nih.gov
authors: Gerald E
authors: GE
authors: Marti
authors: Maryalice
authors: M
authors: Stetler-Stevenson
authors: Nicole Drbohlav
authors: ND
authors: Grant
authors: Therese
authors: T
authors: White
authors: William D
authors: WD
authors: Figg
authors: Tanyifor
authors: T
authors: Tohnya
authors: Elaine S
authors: ES
authors: Jaffe
authors: Kieron
authors: K
authors: Dunleavy
authors: John E
authors: JE
authors: Janik
authors: Seth M
authors: SM
authors: Steinberg
authors: Wyndham H
authors: WH
authors: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D008218:Lymphocytosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019311:Staurosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D001084:Vidarabine Phosphate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate; C054852:7-hydroxystaurosporine; D019311:Staurosporine