1. Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
- Author
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Varterasian ML, Mohammad RM, Shurafa MS, Hulburd K, Pemberton PA, Rodriguez DH, Spadoni V, Eilender DS, Murgo A, Wall N, Dan M, and Al-Katib AM
- Subjects
- Adult, Aged, Antineoplastic Agents adverse effects, Bryostatins, Disease Progression, Fatigue chemically induced, Feasibility Studies, Female, Flow Cytometry, Humans, Immunophenotyping, Lactones adverse effects, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Lymphoma, Non-Hodgkin pathology, Macrolides, Male, Middle Aged, Neoplasm Recurrence, Local, Nervous System Diseases chemically induced, Pain chemically induced, Remission Induction, Treatment Outcome, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Agents therapeutic use, Lactones therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Lymphoma, Non-Hodgkin drug therapy
- Abstract
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.
- Published
- 2000