A phase II consortium trial of vorinostat and bortezomib for advanced soft tissue sarcomas.

Abstract

10075 Background: Two patients with advanced unclassifiable soft tissue sarcoma had tumor shrinkage on a phase I study of vorinostat with bortezomib. Therefore, we assessed this combination in a single-arm phase II investigational study in advanced soft tissue sarcoma patients. Methods: Adults with advanced soft tissue sarcoma, an ECOG performance status ≤ 1, and no more than one prior systemic treatment for advanced stage were eligible. Patients received vorinostat 400 mg orally days 1-14 and bortezomib 1.3 mg/m2 intravenously days 1, 4, 8 and 11 of a 21-day cycle. The primary endpoint was confirmed response rate. Secondary endpoints included toxicity, progression-free survival (PFS) and overall survival (OS). Results: Sixteen patients were enrolled (median age, 62 years; 11 (62%) were women). A total of 53 cycles were received (median, 2 cycles). Fourteen patients were evaluable for response. No confirmed responses were observed, prompting study closure. One patient with synovial sarcoma had a minor response. Six patients had stable disease as best response, including one patient with low-grade myxosarcoma lasting 11 cycles. Median PFS was 1.5 months (95% CI: 1.3-2.9 months) and 6-month OS rate was 85%(95% CI: 67-100%)). Two patients have died, unrelated to treatment. Grade 3 or 4 toxicities, at least possibly related to treatment, included thrombocytopenia (6 patients), diarrhea (6 patients) and fatigue (3 patient). Conclusions: Despite phase I activity with this combination in advanced soft tissue sarcoma, no responses were noted in the phase II setting. Supported by N01-CM-62205.