rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU

Abstract

Summary Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSFprotected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P< 0.005). Five episodes of neutropenia ( < 2 x 109 1-) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.

Dose-intensification of procarbazine, CCNU (lomustine), vincristine (PCV) with peripheral blood stem cell support in young patients with gliomas

“…The currently available growth factors shorten the duration of neutropenia but have little effect on platelet recovery, thereby limiting the ability to increase doseintensity [8,9]. Since CENUs appear to be extremely toxic to primitive hematopoietic stem and progenitor cells [10], we sought to determine whether the use of peripheral blood stem cells could reduce the hematologic toxicity associated with the intensified regimen used by Cairncross et al In addition, we sought to further intensify this regimen by administering the chemotherapy courses every 4 weeks rather than every 6 weeks.…”

Autocrine Growth Regulation by Granulocyte Colony-Stimulating Factor and Granulocyte Macrophage Colony-Stimulating Factor in Human Gliomas with Tumor Progression

“…11 Consequently they now find widespread clinical application in reducing the duration and severity of neutropenic periods in routine cancer therapy. [12][13][14][15] G-CSF and GM-CSF were originally identified as factors controlling proliferation, maturation, and functional activity of granulocytes, macrophages, and their precursors. 16,17 Whereas GM-CSF, a 22-kd glycoprotein, was first defined by its effect in vitro on granulocyte and macrophage colony formation, it is now clear that this factor also acts on multipotent stem cells.…”