A phase II trial of bryostatin 1 in patients with non-Hodgkin's lymphoma

Bryostatin 1 is a naturally occurring macrocyclic lactone with promising an titumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Ho dgkin's lymphoma of indolent type (NHL), previously treated with chemothera py, received a median of 6 (range 1-9) intravenous infusions of 25 mug/m(2) bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 month s. The principal toxicities were myalgia and phlebitis. Treatment was disco ntinued early because of toxicity alone (phlebitis) in 2 patients, toxicity in addition to progressive disease in 3 patients (myalgia and phlebitis n = 2; thrombocytopenia n = 1) and progressive disease in 5 patients. The res ults fail to demonstrate efficacy of this regimen of bryostatin 1 in the tr eatment of NHL. In light of preclinical data that demonstrate synergy betwe en bryostatin 1 and several cytotoxic agents and cytokines, clinical studie s to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studie s to avoid phlebitis. (C) 2001 Cancer Research Campaign.