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.
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.
Authors: B M Curtis; D E Williams; H E Broxmeyer; J Dunn; T Farrah; E Jeffery; W Clevenger; P deRoos; U Martin; D Friend Journal: Proc Natl Acad Sci U S A Date: 1991-07-01 Impact factor: 11.205
Authors: G Morstyn; L Campbell; G Lieschke; J E Layton; D Maher; M O'Connor; M Green; W Sheridan; M Vincent; K Alton Journal: J Clin Oncol Date: 1989-10 Impact factor: 44.544
Authors: J P Laporte; L Fouillard; L Douay; I Eugene-Jolchine; F Isnard; J Stachowiak; A Najman; N C Gorin Journal: Lancet Date: 1991-09-07 Impact factor: 79.321
Authors: S Vadhan-Raj; H E Broxmeyer; W N Hittelman; N E Papadopoulos; S P Chawla; C Fenoglio; S Cooper; E S Buescher; R W Frenck; A Holian Journal: J Clin Oncol Date: 1992-08 Impact factor: 44.544
Authors: J Crawford; H Ozer; R Stoller; D Johnson; G Lyman; I Tabbara; M Kris; J Grous; V Picozzi; G Rausch Journal: N Engl J Med Date: 1991-07-18 Impact factor: 91.245
Authors: W H Wilson; V Jain; G Bryant; K H Cowan; C Carter; M Cottler-Fox; B Goldspiel; S M Steinberg; D L Longo; R E Wittes Journal: J Clin Oncol Date: 1992-11 Impact factor: 44.544
Authors: M Aglietta; W Piacibello; F Sanavio; A Stacchini; F Aprá; M Schena; C Mossetti; F Carnino; F Caligaris-Cappio; F Gavosto Journal: J Clin Invest Date: 1989-02 Impact factor: 14.808