Abstract
Abstract Objective: The molecular targeted drug pazopanib is a selective oral tyrosine kinase inhibitor that exerts its effects on vascular endothelial growth factor receptors (VEGF-R) and inhibits angiogenesis. This study aimed to examine the therapeutic efficacy, incidence of adverse events (AEs), and dosage of pazopanib in Japanese patients with metastatic or unresectable advanced soft tissue sarcoma. Methods: Subjects were 42 patients (16 men and 26 women) with a history of previous anti-cancer agent treatment, who were administered pazopanib for metastatic or unresectable soft tissue sarcoma between November 2012 and August 2014 at our hospital or affiliated hospitals. Pazopanib was administered at an initial dose of 800 mg/day in 25 patients, 600 mg/day in 7 patients, and 400 mg/day in 10 patients; dose was reduced by 200 mg when continuation of treatment was deemed difficult due to the occurrence of grade ≥ 2 AEs. Results: After pazopanib treatment, 6-month and 1-year overall cumulative survival rates were 74.7% and 53.5%, respectively (median survival, 7.7 months). Progression-free survival rates after pazopanib administration were 47.7% at 6 months and 27.0% at 1 year (median survival, 5.0 months). With regard to tumor regression effects, 14 of 42 (33.3%) patients achieved a minor response or better, and the effects were evident even among undifferentiated pleomorphic sarcoma (UPS), malignant peripheral nerve sheath tumor (MPNST), angiosarcoma, and alveolar soft part sarcoma (ASPS). Though AEs due to pazopanib were acceptable, 7% developed grade 3-4 liver dysfunction. All of the 25 patients who started on an initial 800 mg/day dose ended up discontinuing or reducing the medication due to the occurrence of AEs after a mean duration of 34.4 days (median, 17 days). Conclusion: Overall and progression-free median survival after pazopanib administration were 7.7 months and 5.0 months, respectively. Pazopanib proved effective even for UPS, MPNST, angiosarcoma, and ASPS, but continuation of an 800 mg/day dose was difficult among Japanese people.
Highlights
Doxorubicin and ifosfamide were the two key drugs that had been widely used for unresectable advanced recurrent soft tissue sarcoma [1,2] until the recent approval of pazopanib, a molecular targeted drug, for public insurance coverage
Pazopanib proved effective even for undifferentiated pleomorphic sarcoma (UPS), malignant peripheral nerve sheath tumor (MPNST), angiosarcoma, and alveolar soft part sarcoma (ASPS), but continuation of an 800 mg/day dose was difficult among Japanese people
Pazopanib is a selective oral tyrosine kinase inhibitor that acts on vascular endothelial growth factor receptors (VEGF-R)
Summary
Doxorubicin and ifosfamide were the two key drugs that had been widely used for unresectable advanced recurrent soft tissue sarcoma [1,2] until the recent approval of pazopanib, a molecular targeted drug, for public insurance coverage. The use of pazopanib is increasing worldwide [3]. Pazopanib is a selective oral tyrosine kinase inhibitor that acts on vascular endothelial growth factor receptors (VEGF-R). It has been shown to exhibit inhibitory effects on platelet-derived growth factor receptors (PDGFR) and a stem cell factor receptor (c-Kit) [5,6]. Pazopanib was shown to inhibit directly the proliferation of synovial sarcoma cells and block the PI3K-AKT pathway [7].
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