Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant.
Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B-cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50 microg/m(2) given over 24 hr and vincristine 1.4 mg/m(2) on days 1 and 15 every 28 days in aggressive B-cell non-Hodgkin lymphoma (NHL) relapsing after autologous stem cell transplantation. End points included tumor response, toxicity, and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with two patients achieving a complete response. The most common toxicities were Grade 3 lymphopenia (seven patients), Grade 3 to 4 neutropenia (two patients), and Grade 3 hypophosphatemia (two patients). Median progression-free and overall survivals for all patients were 5.7 and 21.4 months, respectively. One patient demonstrated an increase in T-cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine have efficacy in select patients with aggressive NHL. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T-cell apoptosis.
Barr
Paul M
PM
Department of Medicine, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA. paul.barr@uhhospitals.org
Lazarus
Hillard M
HM
Cooper
Brenda W
BW
Schluchter
Mark D
MD
Panneerselvam
Ashok
A
Jacobberger
James W
JW
Hsu
Jack W
JW
Janakiraman
Nalini
N
Simic
Aleksandra
A
Dowlati
Afshin
A
Remick
Scot C
SC
D000368:Aged; D017304:Annexin A5 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D054713:Bryostatins / Q000008:administration & dosage / Q000009:adverse effects; D018956:CD5 Antigens / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000097:blood / Q000517:prevention & control*; D008231:Lymphopenia / Q000097:blood / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism; D012008:Recurrence; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013601:T-Lymphocytes / Q000378:metabolism; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D017304:Annexin A5; D054713:Bryostatins; D018956:CD5 Antigens; C046785:bryostatin 1; D014750:Vincristine; D011493:Protein Kinase C