A phase II trial of bryostatin-1 in patients with metastatic or recurrent squamous cell carcinoma of the head and neck.
Bryostatin-1 is a macrocyclic lactone that has been shown to modulate Protein Kinase C activity and has demonstrated antitumor activity in vitro and in vivo. Fifteen patients with metastatic or recurrent squamous cell carcinoma of the head and neck were treated with bryostatin-1 at a dose of 25 mcg/m2 by continuous intravenous infusion over 24 hours once weekly for three weeks followed by a break week to complete a four-week cycle. There were no major objective responses in the 14 evaluable patients. One patient with nasopharynx cancer had disease stabilization for 4 months prior to being removed from the study due to medical issues. This clinical benefit corresponded to a radiographic decrease in metabolic activity on positron emission tomograpy (PET) scan as well as molecular evidence of tumor apoptosis in a poly[ADP-ribose] polymerase (PARP) cleavage assay. Bryostatin-1 is not recommended for use as a single agent for the treatment of squamous cell head and neck cancer. Further investigation is warranted to determine the strength of the correlation between bryostatin-1 activity and PARP cleavage as a surrogate molecular marker of apoptosis.
Pfister
David G
DG
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
McCaffrey
John
J
Zahalsky
Andrew J
AJ
Schwartz
Gary K
GK
Lis
Eric
E
Gerald
William
W
Huvos
Andrew
A
Shah
Jatin
J
Kraus
Dennis
D
Shaha
Ashok
A
Singh
Bhuvanesh
B
Wolden
Suzanne
S
Zelefsky
Michael
M
Palgi
Ilana
I
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D054713:Bryostatins; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007262:Infusions, Intravenous; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use*; D018942:Macrolides; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1