Phase I study of pazopanib in combination with interferon alfa in patients with advanced renal cell carcinoma (RCC) and other primary tumors: A Spanish Oncology Genitourinary Group (SOGUG) study.

Abstract

450 Background: Pazopanib is a VEGF receptor inhibitor active in the treatment of advanced RCC treatment, and Interferon has been a long-standing treatment option for metastatic RCC with a modest overall survival benefit. The purpose of this study is to assess the feasibility and safety of the combination of pazopanib and interferon in the treatment of advanced RCC and other tumor types. Methods: This is a phase I study of the combination of pazopanib and interferon alfa-2A. It has been developed in a 3+3 standard escalating design with cohorts of 3-6 patients (pts) to identify the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD). Pazopanib is given po daily and interferon is given subcutaneously 3 times a week. Dose levels 1, 2, 3, 4 and 5 corresponded to pazopanib 400, 600, 800, 800 and 800 mg per day plus interferon 3, 3, 3, 6 and 9 million U. Patients with previously treated RCC and also other primary tumors could be included. Results: 19 pts were included and treated in 4 dose levels. Patients’ median age was 60 years old, 13 men and 6 women. Six of them were diagnosed with RCC; other pts presented metastatic tumors as ovarian carcinoma, peritoneal mesothelioma, breast cancer (2), liposarcoma, breast angiosarcoma, uterine sarcomas (3), endometrial carcinoma (3) and melanoma. MTD was reached at level 4, and the RD was Pazopanib 800mg with IFN 3MUI. Three pts experienced DLT, one in level 2 and two in level 4: grade 4 transaminitis, grade 3 transaminitis and grade 3 liver hematoma, respectively. Other toxicities (grade 3 and 4) included anemia, neutropenia, thrombocytopenia, asthenia, arthromialgia, anorexia, diarrhea and Raynaud’s syndrome. Additional mild but common toxicities were fever and proteinuria. One partial response was observed in a uterine sarcoma patient. In RCC, 4 pts achieved stable disease lasting a median of 5 cycles. Conclusions: Combination of pazopanib and interferon alfa is feasible and safe, allowing administration of active doses of both agents. A phase II study to assess this combination activity in RCC is assured. Clinical trial information: NCT01513187.