Peripheral blood progenitor cell cycle kinetics following priming with pIXY321 in patients treated with the 'ICE' regimen
Autor: | J R, Murren, A, Gollerkeri, S, Anderson, S, Lutzker, S, Del Prete, D, Zelterman, L, Garrison, B, Smith |
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Rok vydání: | 1999 |
Předmět: |
Adult
Male Lung Neoplasms Neutropenia Recombinant Fusion Proteins Cell Cycle Granulocyte-Macrophage Colony-Stimulating Factor Middle Aged Hematopoietic Stem Cells Carboplatin Survival Rate Treatment Outcome Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Humans Female Interleukin-3 Ifosfamide Carcinoma Small Cell Aged Etoposide Research Article |
Zdroj: | The Yale Journal of Biology and Medicine |
ISSN: | 0044-0086 |
Popis: | PURPOSE: Treatment with hematopoietic growth factors increases the percentage of hematopoietic progenitor cells in cell cycle. Following withdrawal of certain growth factors, preclinical data suggest that there is a transient fall in the percentage of progenitor cells in cycle below the baseline, thus providing a window to administer chemotherapy with reduced risk of myelotoxicity. PATIENTS AND METHODS: Patients with histologically confirmed, previously untreated neoplasia, were treated with pIXY321 by subcutaneous injection at a dose of 375 microg/m2 twice daily (total dose 750 microg/m2/day) for seven days (days -8 to -2), followed by a two-day rest (days -1 to 0). Patients received ICE (ifosfamide, carboplatin and etoposide) on days 1 to 3. On day 4, pIXY321 was resumed until hematologic recovery. Peripheral blood was collected on days -8, -2, -1, 1, and cell cycle distribution was determined using flow cytometry. RESULTS: Twenty patients were treated in this study and received a total of 54 cycles. Partial responses were observed in three of 13 patients with non-small cell lung cancer (23 percent) and two of five patients with small cell lung cancer (40 percent). Six of 15 patients had an increased number of cells in S+G2/M on day 1 of ICE following seven days of pIXY321 and two days off (days -1 to 0). The average increase was 63 percent (range 6-253). Seven patients had a decreased number of cells in S+G2/M. The average decrease was 55 percent (range 6.3-78). There were no significant differences among the fifteen patients with regards to the observed toxicity of the chemotherapy. DISCUSSION: pIXY321 in this schedule did not consistently decrease the percentage of cycling progenitor cells in the peripheral blood. Future studies should define whether other growth factors and/or schedules can synchronize progenitor cell cycling and protect the marrow compartment from cycle specific chemotherapy. |
Databáze: | OpenAIRE |
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