Peripheral blood progenitor cell cycle kinetics following priming with pIXY321 in patients treated with the "ICE" regimen.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Murren
J R
JR
Yale University School of Medicine and the Yale Cancer Center, New Haven, Connecticut 06520, USA. j.murren@yale.edu
Gollerkeri
A
A
Anderson
S
S
Lutzker
S
S
Del Prete
S
S
Zelterman
D
D
Garrison
L
L
Smith
B
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D018288:Carcinoma, Small Cell / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D002453:Cell Cycle / Q000187:drug effects; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D005047:Etoposide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016190:Carboplatin; D007069:Ifosfamide