Background: To report on the anti-tumour activity and toxicity of sorafenib combined with dacarbazine in patients with pre-treated advanced soft tissue sarcoma (STSs).
Methods: From November 2009 to December 2010, 17 patients affected by STSs who had failed two or more regimen of chemotherapy, with a performance status ≤ 2 and measurable disease were consecutively enrolled in the present case series. Sorafenib was administered at 400 mg b.i.d. continuous dosing in combination with dacarbazine, 300 mg/m(2) for three consecutive days every 21 days until disease progression or intolerable toxicity.
Results: Fourteen patients were evaluable for response. Three patients stopped treatment early and were not evaluable for response. One of them died for not disease-dependent reason, the other two went off-study due to rapid clinical worsening, without performing radiologic evaluation. No complete responses were registered. As by RECIST, partial responses (PR) were observed in three patients (21%), stable disease (SD) in six patients (43%) and progressive disease (PD) in five patients (36%), with a clinical benefit rate (RECIST PR+SD > 6 months) of 64%. The median time of progression was 20 weeks (range: 9 - 34 weeks) and the median overall survival was 43 weeks (range: 17 - 65 weeks). The main toxicities were neutropenia (36%), thrombocytopenia (36%), hypertension (36%), fatigue (50%) and skin reactions (57%). Five patients required dose reductions (both dacarbazine and sorafenib) for toxicity and three patients required only sorafenib reduction for dermatologic reactions. One patient was taken off-study because of severe sorafenib-related dermatologic toxicity.
Conclusions: Sorafenib and dacarbazine combination seems to be an active and safety regimen in pre-treated STSs. A Phase II trial is ongoing in patient affected by selected sarcoma subtypes.