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
- 28 July 2010
- journal article
- clinical trial
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 16 (15), 4024-4030
- https://doi.org/10.1158/1078-0432.ccr-10-0662
Abstract
Purpose: 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. Experimental Design: Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 μg 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. Results: Dose escalation to 1,750 μg 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. Conclusions: Inhalation of GM-CSF at doses from 250 to 1,750 μg twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen. Clin Cancer Res; 16(15); 4024–30. ©2010 AACR.Keywords
This publication has 30 references indexed in Scilit:
- Aerosol Gemcitabine: Preclinical Safety andIn VivoAntitumor Activity in Osteosarcoma-Bearing DogsJournal of Aerosol Medicine and Pulmonary Drug Delivery, 2010
- A Dose-Escalation Study of Aerosolized Sargramostim in the Treatment of Metastatic MelanomaAmerican Journal of Clinical Oncology, 2008
- Corruption of the Fas Pathway Delays the Pulmonary Clearance of Murine Osteosarcoma Cells, Enhances Their Metastatic Potential, and Reduces the Effect of Aerosol GemcitabineClinical Cancer Research, 2007
- Early Lymphocyte Recovery as a Prognostic Indicator for High-risk Ewing SarcomaJournal of Pediatric Hematology/Oncology, 2007
- Treatment of osteosarcoma at first recurrence after contemporary therapyCancer, 2005
- Aerosol gemcitabine inhibits the growth of primary osteosarcoma and osteosarcoma lung metastasesInternational Journal of Cancer, 2005
- Osteosarcoma Relapse After Combined Modality Therapy: An Analysis of Unselected Patients in the Cooperative Osteosarcoma Study Group (COSS)Journal of Clinical Oncology, 2005
- Pattern of disease recurrence and prognostic factors in patients with osteosarcoma treated with contemporary chemotherapyCancer, 2003
- Postrelapse Survival in Osteosarcoma of the Extremities: Prognostic Factors for Long-Term SurvivalJournal of Clinical Oncology, 2003
- Median sternotomy and multiple lung resections for metastatic sarcomasEuropean Journal of Cardio-Thoracic Surgery, 1990