title: A randomized phase II study of BB-10010: a variant of human macrophage inflammatory protein-1alpha for patients receiving high-dose etoposide and cyclophosphamide for malignant lymphoma and breast cancer.
abstract: Macrophage inflammatory protein-1alpha (MIP-1alpha) is a chemokine that can inhibit the cell cycle progression of both primitive haemopoietic and epidermal progenitor cells. This property could potentially be exploited to attenuate both the myelosuppressive effects of chemotherapy as well as mucositis. We evaluated both the biological and clinical effects of BB-10010, a genetically engineered variant of MIP-1alpha, in patients with malignant lymphoma or breast cancer receiving high-dose etoposide (VP 3.6 g/m2) and cyclophosphamide (Cy 200 mg/kg). 52 patients were randomized to one of three cohorts. Cohort A received no BB-10010; cohorts B and C received 10 microg/kg and 100 microg/kg of BB-10010, respectively. All patients received post-chemotherapy G-CSE BB-10010 was well tolerated. There were no significant differences between groups in recovery to an ANC > 0.5 x 10(9)/l, 1 x 10(9)/l or 1.5 x 10(9)/l, the number of days with an ANC < 0.5 x 10(9)/l, days to a platelet count > 50 x 10(9)/l or 100 x 10(9)/l, or the incidence and severity of mucositis. There was no evidence of any effect of BB-10010 on colony-forming cell (CFC) or long-term culture-initiating cell (LTC-IC) mobilization, cycling activity in the marrow or on chemotherapy-induced changes in CFC or LTC-IC number both of which were in the normal range by 22 d after completion of the chemotherapy. To our knowledge this is the first report of a myelointensive regimen having no apparent long-term effect on the LTC-IC compartment. In summary, BB-10010 is safe when used in patients receiving high-dose therapy but has no effect on reducing the toxicity of such therapy.
authors.affiliation: Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Bernstein
authors.forename: C J
authors.initials: CJ
authors.lastname: Eaves
authors.forename: R
authors.initials: R
authors.lastname: Herzig
authors.forename: J
authors.initials: J
authors.lastname: Fay
authors.forename: J
authors.initials: J
authors.lastname: Lynch
authors.forename: G L
authors.initials: GL
authors.lastname: Phillips
authors.forename: N
authors.initials: N
authors.lastname: Christiansen
authors.forename: D
authors.initials: D
authors.lastname: Reece
authors.forename: S
authors.initials: S
authors.lastname: Ericson
authors.forename: M
authors.initials: M
authors.lastname: Stephan
authors.forename: M
authors.initials: M
authors.lastname: Kovalsky
authors.forename: K
authors.initials: K
authors.lastname: Hawkins
authors.forename: H
authors.initials: H
authors.lastname: Rasmussen
authors.forename: A
authors.initials: A
authors.lastname: Devos
authors.forename: G P
authors.initials: GP
authors.lastname: Herzig
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000628:therapy*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D019402:Macrophage Inflammatory Proteins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D013280:Stomatitis / Q000139:chemically induced / Q000517:prevention & control
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006131:Growth Inhibitors; D019402:Macrophage Inflammatory Proteins; D005047:Etoposide; D003520:Cyclophosphamide