title: Sorafenib and dacarbazine in soft tissue sarcoma: a single institution experience.
abstract: 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.
authors.affiliation: University Campus Bio Medico, Rome, Italy. b.vincenzi@unicampus.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Marianna
authors.initials: M
authors.lastname: Silletta
authors.forename: Gaia
authors.initials: G
authors.lastname: Schiavon
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.forename: Raimondo
authors.initials: R
authors.lastname: Del Vescovo
authors.forename: Bruno Beomonte
authors.initials: BB
authors.lastname: Zobel
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Angelo Paolo
authors.initials: AP
authors.lastname: Dei Tos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D003606:Dacarbazine; D000077157:Sorafenib