A phase i trial of subcutaneous (SC) BB-10010 in breast. Cancer patients (PTS) receiving high-dose cyclophosphamide (C)

M. S. Gordon, W. J. McCaskill-Stevens, H. E. Broxmeyer

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1 Scopus citations

Abstract

We have completed a phase I trial of BB-10010 (a MIP-ia analog) in women with breast cancer. SB-10010 was administered to cohorts of 3-5 women at doses of 5, 10, 30, and 100 (ag/kg/d SC for 3 days (d 0-2) during a prechemotherapy safety cycle. Subsequently, all patients received up to six 21 -day cycles (cy) with BB-10010 at their assigned dose SC for 3 days (d 0-2) with C (3 grn/m2 on d 1). In Cy 1, pts receive C+BB-10010 alone while in Cy 2-6 they receive C+BB-10010+G-CSF. Sixteen pts have been accrued to the 5-100 jig/kg levels. During Cy 0, no dose-limiting grade 3 or 4 adverse events (AE) rotated to BB-10010 were seen. Four pts were removed due to a skin reaction (1 OS (ig/kg), meligibiiity (1 @ 10 jig/kg), and progressive disease {2 & 100 jig/kg); all were replaced. Grade 1 or 2 AE included constitutional symptoms of headache and fatigue in 2 pts. Bone marrow (BM) evaluations prior to and following 3d of BB-10010 revealed a statistically significant decrease in the S-phase of BM progenitors from a rapidly proliferating to a slow or non-cycling state at all doses. We assessed the reversibility of these effects in the 100 ng/kg cohort with a BM on o9 and found that cell cycling was recovered to pre-treatment levels in all patients studied. No changes in BM differentials or morphology were noted. While no significant effects were seen on peripheral blood counts, an average 23-fold increase in peripheral blood progenitor cells (PBPC) was seen during the administration of BB-10010 in Cy 0- In Cy 1, no dose-related effects of BB-10010 on the myelosuppression of C were seen and mean nadir neutrophil counts in Cy 1 were <100 cells/Ml in all cohorts. While the duration of neutropenia was shortened by G-CSF in cycles 2-6. no definitive effects of BB-10010 could be identified. We conclude that BB-10010 is safe and that its administration significantly reversibly reduces the percentage of BM cells in S-phase and induces mobilization of PBPC.

Original languageEnglish (US)
Number of pages1
JournalExperimental Hematology
Volume24
Issue number9
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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