pazopanib and Sarcoma--Ewing

Ewing's sarcoma (ES)/primitive neuroectodermal tumors (PNETs) are highly malignant neoplasms that usually affect the bones and soft tissues in children and young adults. ES/PNET of the lung is very rare and is associated with a poor prognosis. We herein report a case of ES/PNET of the left lung in a 45-year-old man. He was treated with neoadjuvant chemotherapy and pneumonectomy, but unfortunately his disease recurred 1.5 months after surgery. He was started on pazopanib, which resulted in a five-month progression-free survival. To our knowledge, this is the first demonstration of pazopanib efficacy in ES/PNET of the lung.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Fatal Outcome; Humans; Indazoles; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neuroectodermal Tumors, Primitive; Pneumonectomy; Progression-Free Survival; Pyrimidines; Sarcoma, Ewing; Sulfonamides; Treatment Outcome

The clinical efficacy and outcomes of pazopanib treatment for metastatic extraosseous Ewing sarcoma remain unclear. We herein report a case of heavily pre-treated metastatic extraosseous Ewing sarcoma in which pazopanib treatment achieved a significant improvement. A 17-year-old girl was referred to our hospital due to metastatic extraosseous Ewing sarcoma. The initial cytotoxic chemotherapy was temporarily effective, however, her disease eventually progressed, and she was subsequently treated with pazopanib. The recurrent tumor showed a marked response to pazopanib therapy; the therapeutic effect has lasted for more than 26 months. The present case suggests that pazopanib may be a therapeutic option for extraosseous Ewing sarcoma.

Topics: Adolescent; Angiogenesis Inhibitors; Antineoplastic Agents; Bone Neoplasms; Female; Humans; Indazoles; Lung Neoplasms; Pyrimidines; Sarcoma, Ewing; Sulfonamides; Vaginal Neoplasms

Topics: Angiogenesis Inhibitors; Bone Neoplasms; Female; Humans; Indazoles; Neoplasm Recurrence, Local; Pyrimidines; Salvage Therapy; Sarcoma, Ewing; Sulfonamides; Young Adult

Topics: Fatal Outcome; Humans; Indazoles; Male; Middle Aged; Neoplasm Recurrence, Local; Pyrimidines; Retroperitoneal Neoplasms; Sarcoma, Ewing; Sulfonamides

Pazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor-1, -2, and -3, platelet derived growth factor receptor-α, platelet derived growth factor receptor-β, and KIT that has demonstrated activity against a variety of adult cancer xenografts. Pazopanib was tested against a panel of pediatric rhabdomyosarcoma and Ewing sarcoma xenografts at a dose of 108 mg/kg/day or 100 mg/kg twice daily, administered orally for 28 days. While no objective responses were observed, pazopanib induced statistically significant differences in event-free survival compared to controls in approximately one-half of the sarcoma xenograft models tested. Though well tolerated, pazopanib showed limited activity against the sarcoma models evaluated, with the best tumor responses being growth delay.

Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Child; Child, Preschool; Female; Humans; Indazoles; Mice; Mice, SCID; Protein Kinase Inhibitors; Pyrimidines; Receptor, Platelet-Derived Growth Factor beta; Rhabdomyosarcoma; Sarcoma, Ewing; Sulfonamides; Vascular Endothelial Growth Factors; Xenograft Model Antitumor Assays