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
| Autor: | Darryl C. Grendahl, Nadya V. Koshkina, Allen M. Goorin, Carola A.S. Arndt, Martin L. Blakely, Mark L. Bernstein, Mark Krailo, Carrie Y. Inwards, Sharon A. Bell, Peter M. Anderson, Douglas S. Hawkins, Doojduen Villaluna, Neyssa Marina, Kaylee Ray, Eugenie S. Kleinerman |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Lung Neoplasms Adolescent medicine.medical_treatment Antineoplastic Agents Bone Neoplasms Kaplan-Meier Estimate Gastroenterology Disease-Free Survival Article Fas ligand Immunomodulation Young Adult Internal medicine Administration Inhalation medicine Humans Thoracotomy Child Osteosarcoma Lung business.industry Granulocyte-Macrophage Colony-Stimulating Factor Cancer medicine.disease Surgery Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Oncology Toxicity Feasibility Studies Female Sarcoma business medicine.drug |
| Zdroj: | Clinical Cancer Research. 16:4024-4030 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-10-0662 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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