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.
Blackhall
F H
FH
CRC Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK.
Ranson
M
M
Radford
J A
JA
Hancock
B W
BW
Soukop
M
M
McGown
A T
AT
Robbins
A
A
Halbert
G
G
Jayson
G C
GC
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