Pazopanib, a Multikinase Angiogenesis Inhibitor, in Patients With Relapsed or Refractory Advanced Soft Tissue Sarcoma: A Phase II Study From the European Organisation for Research and Treatment of Cancer―Soft Tissue and Bone Sarcoma Group (EORTC Study 62043)

摘要: PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral inhibitor that targets vascular endothelial growth factor receptor and platelet-derived receptor, was explored patients with advanced STS. PATIENTS AND METHODS Patients intermediate- or high-grade STS who were ineligible for chemotherapy had received no more than two prior cytotoxic agents disease, documented progression, adequate performance status, good organ function eligible. Pazopanib 800 mg given daily. The primary end point progression-free rate at 12 weeks (PFR(12 weeks)). Secondary points response, safety, overall survival. Four different strata studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, other types. A Simon two-stage design applied (P1 = 40%; P0 20%; alpha beta .1) each stratum. Results One hundred forty-two enrolled. stratum closed after first stage, insufficient activity weeks), five [26%] of19). PFR(12 weeks) 18 (44%) 41 leiomyosarcoma cohort, (49%) 37 16 (39%) Compared historical controls treated second-line chemotherapy, survivals prolonged three cohorts which reached. most frequent drug-related toxicities hypertension, fatigue, hypopigmentation, nausea. Other included liver enzyme elevations, myelosuppression, proteinuria, all mostly grades 1 to 2. 3 4 hyperbilirubinemia (6.3%), hypertension (7.7%), fatigue (7.7%). CONCLUSION is well tolerated relapsed, demonstrates interesting warrants additional study