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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92043
Title:
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.
Authors:
Clemons, Mark; Marshall, E; Dürig, J; Watanabe, K; Howell, Anthony ( 0000-0002-3879-5991 ) ; Miles, D; Earl, H; Kiernan, Julie; Griffiths, Audrey; Towlson, K; DeTakats, P; Testa, Nydia G; Dougal, Mark; Hunter, M G; Wood, L M; Czaplewski, L G; Millar, A; Dexter, T Michael; Lord, Brian I
Abstract:
BB-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.
Affiliation:
CRC Department of Medical Oncology and Paterson Institute for Cancer Research, Christie Hospital, Manchester; ICRF Clinical Oncology Unit, Guy's Hospital, London.
Citation:
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. 1998, 92 (5):1532-40 Blood
Journal:
Blood
Issue Date:
1-Sep-1998
URI:
http://hdl.handle.net/10541/92043
PubMed ID:
9716580
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorClemons, Marken
dc.contributor.authorMarshall, Een
dc.contributor.authorDürig, Jen
dc.contributor.authorWatanabe, Ken
dc.contributor.authorHowell, Anthonyen
dc.contributor.authorMiles, Den
dc.contributor.authorEarl, Hen
dc.contributor.authorKiernan, Julieen
dc.contributor.authorGriffiths, Audreyen
dc.contributor.authorTowlson, Ken
dc.contributor.authorDeTakats, Pen
dc.contributor.authorTesta, Nydia Gen
dc.contributor.authorDougal, Marken
dc.contributor.authorHunter, M Gen
dc.contributor.authorWood, L Men
dc.contributor.authorCzaplewski, L Gen
dc.contributor.authorMillar, Aen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorLord, Brian Ien
dc.date.accessioned2010-02-12T16:29:11Z-
dc.date.available2010-02-12T16:29:11Z-
dc.date.issued1998-09-01-
dc.identifier.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 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid9716580-
dc.identifier.urihttp://hdl.handle.net/10541/92043-
dc.description.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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectHaematopoiesisen
dc.subjectHaematopoitic Stem Cellsen
dc.subjectCancer Metastasisen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshBone Marrow Cells-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCell Count-
dc.subject.meshCells, Cultured-
dc.subject.meshChemokine CCL3-
dc.subject.meshChemokine CCL4-
dc.subject.meshCyclophosphamide-
dc.subject.meshDoxorubicin-
dc.subject.meshFemale-
dc.subject.meshFluorouracil-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshLeukocyte Count-
dc.subject.meshMacrophage Inflammatory Proteins-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshNeutrophils-
dc.titleA randomized phase-II study of BB-10010 (macrophage inflammatory protein- 1alpha) in patients with advanced breast cancer receiving 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology and Paterson Institute for Cancer Research, Christie Hospital, Manchester; ICRF Clinical Oncology Unit, Guy's Hospital, London.en
dc.identifier.journalBlooden

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