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 microg/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 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.
CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK.
F H
FH
Blackhall
M
M
Ranson
J A
JA
Radford
B W
BW
Hancock
M
M
Soukop
A T
AT
McGown
A
A
Robbins
G
G
Halbert
G C
GC
Jayson
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D054713:Bryostatins; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D010689:Phlebitis / Q000139:chemically induced*; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1