title: Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant.
abstract: 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.
authors.affiliation: Department of Medicine, Case Comprehensive Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA. paul.barr@uhhospitals.org
authors.forename: Paul M
authors.initials: PM
authors.lastname: Barr
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Cooper
authors.forename: Mark D
authors.initials: MD
authors.lastname: Schluchter
authors.forename: Ashok
authors.initials: A
authors.lastname: Panneerselvam
authors.forename: James W
authors.initials: JW
authors.lastname: Jacobberger
authors.forename: Jack W
authors.initials: JW
authors.lastname: Hsu
authors.forename: Nalini
authors.initials: N
authors.lastname: Janakiraman
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Simic
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
mesh_terms: 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
chemical_list: D017304:Annexin A5; D054713:Bryostatins; D018956:CD5 Antigens; C046785:bryostatin 1; D014750:Vincristine; D011493:Protein Kinase C