Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype.
Varterasian
M L
ML
Karmanos Cancer Institute and Wayne State University, Detroit, Michigan 48201, USA.
Mohammad
R M
RM
Shurafa
M S
MS
Hulburd
K
K
Pemberton
P A
PA
Rodriguez
D H
DH
Spadoni
V
V
Eilender
D S
DS
Murgo
A
A
Wall
N
N
Dan
M
M
Al-Katib
A M
AM
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054713:Bryostatins; D018450:Disease Progression; D005221:Fatigue / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009422:Nervous System Diseases / Q000139:chemically induced; D010146:Pain / Q000139:chemically induced; D012074:Remission Induction; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D014750:Vincristine