A randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy.
Testa, Nydia G
Hunter, M G
Wood, L M
Czaplewski, L G
Dexter, T Michael
Lord, Brian I
AffiliationCRC Department of Medical Oncology and Paterson Institute for Cancer Research, Christie Hospital, Manchester; ICRF Clinical Oncology Unit, Guy's Hospital, London.
MetadataShow full item record
AbstractBB-10010 is a variant of the human form of macrophage inflammatory protein-1alpha (MIP-1alpha), which has been shown in mice to block the entry of hematopoietic stem cells into S-phase and to increase their self-renewal capacity during recovery from cytotoxic damage. Its use may constitute a novel approach for protecting the quality of the stem cell population and its capacity to regenerate after periods of cytotoxic treatment. Thirty patients with locally advanced or metastatic breast cancer were entered into the first randomized, parallel group controlled phase II study. This was designed to evaluate the potential myeloprotective effects of a 7-day regimen of BB-10010 administered to patients receiving six cycles of 5-fluorouracil (5-FU), adriamycin, and cyclophosphamide (FAC) chemotherapy. Patients were randomized, 10 receiving 100 microgram/kg BB-10010, 11 receiving 30 microgram/kg BB-10010, and nine control patients receiving no BB-10010. BB-10010 was well-tolerated in all patients with no severe adverse events related to the drug. Episodes of febrile neutropenia complicated only 4% of the treatment cycles and there was no difference in incidence between the treated and nontreated groups. Studies to assess the generation of progenitor cells in long-term bone marrow cultures were performed immediately preceding chemotherapy and at the end of six dosing cycles in 18 patients. Circulating neutrophils, platelets, CD 34(+) cells, and granulocyte/macrophage colony-forming cell (GM-CFC) levels were determined at serial time points in cycles 1, 3, and 6. The results showed similar hemoglobin and platelet kinetics in all three groups. On completion of the six treatment cycles, the average pretreatment neutrophil levels were reduced from 5.3 to 1.7 x 10(9)/L in the control patients and from 4.3 to 1.9 and 4.5 to 2.5 x 10(9)/L in the 30/100 microgram/kg BB-10010 groups, respectively. Relative to their pretreatment values, 50% of the patients receiving BB-10010 completed the treatment with neutrophil values significantly higher than any of the controls (P = .02). Mobilization of GM-CFC was enhanced by BB-10010 with an additional fivefold increase over that generated by chemotherapy alone, giving a maximal 25-fold increase over pretreatment values. Bone marrow progenitor assays before and after this standard regimen of chemotherapy indicated little long-term cumulative impairment to recovery from chemotherapy. Despite the limited cumulative damage to the bone marrow, which may have minimized the protective value of BB-10010 during this regimen of chemotherapy, better recovery of neutrophils in the later treatment cycles with BB-10010 was indicated in a number of patients.
CitationA randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy. 1998, 92 (5):1532-40 Blood
- Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.
- Authors: Stewart FM, Temeles D, Lowry P, Thraves T, Grosh WW, Quesenberry PJ
- Issue date: 1993 May 1
- Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer.
- Authors: O'Shaughnessy JA, Tolcher A, Riseberg D, Venzon D, Zujewski J, Noone M, Gossard M, Danforth D, Jacobson J, Chang V, Goldspiel B, Keegan P, Giusti R, Cowan KH
- Issue date: 1996 Mar 15
- Myeloid progenitor cell proliferation and mobilization effects of BB10010, a genetically engineered variant of human macrophage inflammatory protein-1alpha, in a phase I clinical trial in patients with relapsed/refractory breast cancer.
- Authors: Broxmeyer HE, Orazi A, Hague NL, Sledge GW Jr, Rasmussen H, Gordon MS
- Issue date: 1998 Mar
- 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.
- Authors: Bernstein SH, Eaves CJ, Herzig R, Fay J, Lynch J, Phillips GL, Christiansen N, Reece D, Ericson S, Stephan M, Kovalsky M, Hawkins K, Rasmussen H, Devos A, Herzig GP
- Issue date: 1997 Dec
- Hematological recovery and peripheral blood progenitor cell mobilization after induction chemotherapy and GM-CSF plus G-CSF in breast cancer.
- Authors: Charrier S, Chollet P, Bay JO, Curé H, Kwiatkowski F, Portefaix G, Communal Y, Bétail G, Plagne R, Chassagne J
- Issue date: 2000 Apr