title: Dacarbazine in solitary fibrous tumor: a case series analysis and preclinical evidence vis-a-vis temozolomide and antiangiogenics.
abstract: OBJECTIVE
  To explore the value of triazines in solitary fibrous tumor (SFT).
  
  
  METHODS
  We retrospectively reviewed 8 cases of patients with SFT treated with dacarbazine (1,200 mg/m(2) 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 mm(3); 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.
authors.affiliation: Authors' Affiliations: Adult Sarcoma Medical Oncology Unit, Department of Cancer Medicine; Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine; Experimental Molecular Pathology Unit, Department of Pathology; Department of Radiology; and Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Stacchiotti
authors.forename: M
authors.initials: M
authors.lastname: Tortoreto
authors.forename: F
authors.initials: F
authors.lastname: Bozzi
authors.forename: E
authors.initials: E
authors.lastname: Tamborini
authors.forename: C
authors.initials: C
authors.lastname: Morosi
authors.forename: A
authors.initials: A
authors.lastname: Messina
authors.forename: M
authors.initials: M
authors.lastname: Libertini
authors.forename: E
authors.initials: E
authors.lastname: Palassini
authors.forename: D
authors.initials: D
authors.lastname: Cominetti
authors.forename: T
authors.initials: T
authors.lastname: Negri
authors.forename: A
authors.initials: A
authors.lastname: Gronchi
authors.forename: S
authors.initials: S
authors.lastname: Pilotti
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: P G
authors.initials: PG
authors.lastname: Casali
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D054364:Solitary Fibrous Tumors / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology*; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068258:Bevacizumab; D003606:Dacarbazine; C516667:pazopanib; D000077210:Sunitinib; D000077204:Temozolomide