Cancer Institute A national cancer institute
designated cancer center

Neyssa Marina

Publication Details

  • Inhaled Granulocyte-Macrophage Colony Stimulating Factor for First Pulmonary Recurrence of Osteosarcoma: Effects on Disease-Free Survival and Immunomodulation. A Report From the Children's Oncology Group CLINICAL CANCER RESEARCH Arndt, C. A., Koshkina, N. V., Inwards, C. Y., Hawkins, D. S., Krailo, M. D., Villaluna, D., Anderson, P. M., Goorin, A. M., Blakely, M. L., Bernstein, M., Bell, S. A., Ray, K., Grendahl, D. C., Marina, N., Kleinerman, E. S. 2010; 16 (15): 4024-4030

    Abstract:

    Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma.Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks. Following two cycles, patients underwent thoracotomy to resect tumor and analyze pulmonary nodules for expression of Fas/Fas ligand (Fas/FasL), and the presence of dendritic cells by immunostaining for CD1a, clusterin, and S100. Following surgery, patients received 12 additional cycles of therapy on alternating weeks or until progression. Event-free survival and survival, and feasibility of therapy delivery were evaluated.Dose escalation to 1,750 microg twice daily was feasible with no dose-limiting toxicity. Mean scores for Fas/FasL in nodules from patients with bilateral recurrence who underwent unilateral thoracotomy pretreatment (using a scoring system of 0-3) were 1.3 and 0.88, respectively, compared with 0.78 and 0.62 in nodules resected following two cycles of therapy. Only 11 of 30 nodules postinhalation were positive for CD1a, 4 of 30 for S100, and 6 of 30 for clusterin. Event-free and overall survival at 3 years were 7.8% and 35.4%, respectively.Inhalation of GM-CSF at doses from 250 to 1,750 microg twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen.

    View details for DOI 10.1158/1078-0432.CCR-10-0662

    View details for Web of Science ID 000280530300023

    View details for PubMedID 20576718

Stanford Medicine Resources:

Footer Links: