PDF file, 256K, A Human primary tumor: morphology (i.e., patternless growth, collagen deposition, moderate cellularity, mitotic index (>4X10 High Power Field (HPF), as shown in panel 1) and immunophenotype (i.e., diffuse positivity for CD34, as shown in panel 1/a) were consistent with a malignant SFT. Immunohistochemistry was positive for PDGFRB expression (panel 1/b). B Human relapsed tumor: morphology was consistent with a dedifferentiated SFT (DSFT), being marked by the abrupt transition from areas with MSFT aspects similar to what observed in the primary tumor (panel 2) to areas with high-grade sarcoma features (panel 3). High-grade areas showed hypercellularity (panel 3/a), chondroid (panel 3/b) and osteoid differentiation (panel 3/c). C Xenograft tumor: morphology was consistent with a high-grade DSFT (panel 4), superimposable to what observed in panel B, 3a/3b/3c, again with presence of mineralized trabeculaes and osteoid (panel 4/a). Immunohistochemistry was positive for PDGFRB expression (panel 4/b). Phospho receptor tyrosine kinase (pRTK) array (ARY001 Proteome ProfilerTM Array, R&D Systems) showed similar profiles for human relapsed tumor (panel B, 3/d) and xenograft (panel C, 4/c) with the activation of PDGFRA (green boxes), PDGFRB (red boxes) and VEGFR1 (yellow boxes). White boxes are the proteome profiler negative controls.
ARTICLE ABSTRACT
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 (1,200 mg/m2 every 3 weeks) 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 when mean tumor volume (TV) was about 80 mm3; each experimental groups included 6 mice. 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.
