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

Bryostatin 1 is a naturally occurring macrocyclic lactone with promising antitumour and immunomodulatory function in preclinical and phase I clinical investigations. In this phase II study, 17 patients with progressive non-Hodgkin's lymphoma of indolent type (NHL), previously treated with chemotherapy, received a median of 6 (range 1–9) intravenous infusions of 25 μg/m2bryostatin 1 given once weekly over 24 hours. In 14 evaluable patients no responses were seen. Stable disease was attained in one patient for 9 months. The principal toxicities were myalgia and phlebitis. Treatment was discontinued 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 results fail to demonstrate efficacy of this regimen of bryostatin 1 in the treatment of NHL. In light of preclinical data that demonstrate synergy between bryostatin 1 and several cytotoxic agents and cytokines, clinical studies to investigate bryostatin 1 in combination are warranted. We also present data to demonstrate that central venous lines may be used in future studies to avoid phlebitis. © 2001 Cancer Research Campaign http://www.bjcancer.co

Phase II trial of temozolomide in low-grade non-Hodgkin's lymphoma.

Temozolomide, an imidazotetrazine derivative, was given to 18 patients with low-grade non-Hodgkin's lymphoma (NHL) at a dose of 750 mg m-2 orally, divided over five consecutive days, escalated to 1000 mg m-2 over 5 days (i.e. 200 mg m-2 day-1) if no significant myelosuppression was noted at day 22 of the 28 day cycle. Fifty-six treatment cycles were given to 18 patients. The drug was well tolerated. Only one partial tumour response was documented. The patients were heavily pretreated but had chemoresponsive disease, as shown by a response rate of 69% among 13 patients who went on to receive alternative cytotoxic regimens. We conclude that temozolomide given in this schedule is inactive in previously treated low-grade NHL