Ml. Varterasian et al., Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia, CLIN CANC R, 6(3), 2000, pp. 825-828
Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula
neritina in 1982 and is currently undergoing evaluation in a number of mali
gnancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymph
oma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h cont
inuous infusion every 2 weeks at a dose of 120 mu g/m(2) per course. Patien
ts who progressed while receiving bryostatin 1 alone could participate in a
feasibility study by receiving vincristine administered by bolus i.v. inje
ction immediately after the completion of the bryostatin 1 infusion. The do
se of vincristine was escalated in groups of three patients as follows: lev
el 1, 0.5 mg/m(2); level 2, 1.0 mg/m(2); and level 3, 1.4 mg/m(2) with vinc
ristine doses capped at 2.0 mg for all patients, Bryostatin 1 alone resulte
d in one complete remission and two partial remissions. Nine patients recei
ved sequential treatment with bryostatin 1 and vincristine, The addition of
vincristine at a dose of 2 mg was feasible and caused the expected dose-re
lated sensory neuropathy, Phenotypic analysis by flow cytometric analysis o
n pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed
up-regulation in the coexpression of CD11c/CD22 on CD20(+) B cells in two o
f four CLL patients studied, which is consistent with in vitro findings of
differentiation of CLL cells to a hairy cell phenotype.