The Significant Effects of Pazopanib on Multiple Pulmonary Metastatic Lesions of Alveolar Soft Part Sarcoma: A Case Report
Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor that usually occurs in children and adolescents. It often causes metastases that are refractory to conventional chemotherapy.1 Therapies targeting multiple tyrosine kinase inhibitors or antiangiogenic therapies have been reported in ASPS.2
We herein report an adolescent case of ASPS with multiple lung metastases that significantly responded to pazopanib.
An 11-year-old girl presented to our hospital with tenderness and a slowly growing mass in the right thigh. Magnetic resonance imaging showed an invasive hypervascular 7×5×3 cm tumor of her right thigh, and computed tomography revealed multiple lung metastases. She underwent incisional biopsy of the primary tumor. On a microscopic examination, alveolar-like proliferation and invasion of cytoplasmic-rich large tumor cells were seen. The nuclei were positive for TFE3 on immunostaining. The pathologic diagnosis was confirmed as ASPS. After wide surgical resection of the primary tumor, she received 2 courses of chemotherapy consisting of ifosfamide, adriamycin, and vincristine, but showed no improvement. She was observed without any treatment for the next 2 years. The lung lesions slowly enlarged thereafter, so she was administered 600 mg/d (450 mg/m2) of pazopanib at 14 years of age. The dose of pazopanib was referenced from the phase 1 study conducted by the Children’s Oncology Group.3 Marked improvement of her multiple lung lesions was observed upon pazopanib treatment (Fig. 1), although adverse effects such as loss and decoloration of hair, hypertension, fatigue, and myalgia also developed. The dose was reduced to 400 mg per day 5 months after the start of pazopanib due to these adverse effects. The multiple lung lesions slowly began growing again at 3 months after the dose reduction.
ASPS exhibits an unbalanced chromosomal translocation t(X;17)(p11;q25), leading to the generation of a chimeric transcription factor ASPL-TFE3 that upregulates the expression of the met proto-oncogene (MET) receptor tyrosine kinase. Although MET was expected to be a therapeutic target for ASPS, treatment with the MET inhibitor tivantinib did not result in tumor shrinkage.4 This could be due to upregulation of compensatory pathways for the growth and survival of the tumor. Gene expression profiling studies of ASPS have revealed upregulation of angiogenesis-related molecules.5 The antitumor activities of multiple tyrosine kinase inhibitors or antiangiogenic therapies have been reported in ASPS. Cediranib, an all-3 vascular endothelial growth factor receptor inhibitor, or sunitinib, a multitargeted kinase inhibitor, have demonstrated antitumor activity in ASPS.2,6
Pazopanib is a multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-kit. Pazopanib has therapeutic potential in patients with advanced soft tissue sarcomas, but little is known of its activity against ASPS.7 Two pediatric ASPS patients were included in the phase 1 study of pazopanib with stable disease.3 In our case, pazopanib showed significant effects against multiple pulmonary metastatic lesions. Pazopanib can be useful for the treatment of ASPS; however, the long-term safety of pazopanib in children remains unknown. More data are needed to evaluate the efficacy and safety of pazopanib for ASPS in children.