Cancer Therapy: Clinical Dacarbazine in Solitary Fibrous Tumor: A Case Series Analysis and Preclinical Evidence vis- a-vis Temozolomide and Antiangiogenics

Purpose: To explore the value of triazines in solitary fibrous tumor (SFT). Experimental Design:We retrospectively reviewed 8 cases of patients with SFT treated with dacarbazine (1,200mg/m every 3weeks) as from January 2012. Then,we studied a dedifferentiated-SFT subcutaneously xenotransplanted into severe combined immunodeficient (SCID) mice. Dacarbazine, temozolomide, sunitinib, bevacizumab, and pazopanib were administered at their reported optimal doses for the mouse model whenmean tumor volume (TV)was about 80mm; each experimental groups included 6mice.Drug activity was assessed as tumor volume inhibition percentage (TVI%). Dacarbazine was tested according to two different schedules of administration. One hunded twenty days after treatment interruption, mouse tumor samples were analyzed. Results: Among the eight patients treated with dacarbazine, best response evaluation criteria in solid tumors responses (RECIST) were three partial responses, 4 stable disease, 1 progression. Two responsive patients had paraneoplastic hypoglycemia that disappeared after 10 days from starting dacarbazine. In the dedifferentiated-SFT xenograft model, dacarbazine and temozolomide showed the highest antitumor activity (about 95% TVI), confirmed pathologically. Sunitinib and pazopanib were only marginally active (52% and 41% TVI, respectively), whereas bevacizumab caused a 78% TVI. No tumor regrowth was observed up to 100 days from end of treatment with temozolomide and dacarbazine, whereas secondary progression followed sunitinib, pazopanib, and bevacizumab interruption. Conclusions:Dacarbazine as single agent has antitumor activity in SFT. Our preclinical results suggest a cytotoxic effect of temozolomide and dacarbazine, as compared with a cytostatic role for sunitinib, pazopanib, and bevacizumab. A phase II study on dacarbazine in advanced SFT is planned. Clin Cancer Res; 19(18); 5192–201. 2013 AACR.