title: Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies.
abstract: METHODS
  The safety of oral sorafenib up to a maximum protocol-specified dose combined with dacarbazine in patients with metastatic, histologically confirmed melanoma was investigated in a phase I dose-escalation study and the activity of the combination was explored in an open-label phase II study.
  
  
  RESULTS
  In the phase I study, three patients were treated with sorafenib 200 mg twice daily (b.i.d.) plus 1000 mg m(-2) dacarbazine on day 1 of a 21-day cycle and 15 patients had the sorafenib dose escalated to 400 mg b.i.d. without reaching the maximum tolerated dose of the combination. In the phase II study (n=83), the overall response rate was 12% (95% CI: 6, 21): one complete and nine partial, with median response duration of 46.7 weeks. Stable disease was the best response in 37%; median duration was 13.3 weeks. Median overall survival (OS) was 37.0 weeks (95% CI: 33.9, 46.0).
  
  
  CONCLUSIONS
  Oral sorafenib combined with dacarbazine had acceptable toxicity and some antineoplastic activity against metastatic melanoma.
authors.affiliation: Department of Oncology (R4), Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. tgqe2@cam.ac.uk
authors.forename: T
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authors.lastname: Eisen
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authors.lastname: Marais
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authors.lastname: Affolter
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authors.lastname: Lorigan
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authors.lastname: Robert
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authors.lastname: Corrie
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authors.lastname: Ottensmeier
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authors.lastname: Chevreau
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authors.lastname: Chao
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authors.lastname: Nathan
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authors.lastname: Jouary
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authors.lastname: Harries
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authors.lastname: Negrier
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authors.initials: E
authors.lastname: Montegriffo
authors.forename: T
authors.initials: T
authors.lastname: Ahmad
authors.forename: I
authors.initials: I
authors.lastname: Gibbens
authors.forename: M G
authors.initials: MG
authors.lastname: James
authors.forename: U P
authors.initials: UP
authors.lastname: Strauss
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mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D003606:Dacarbazine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077157:Sorafenib
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D003606:Dacarbazine; D000077157:Sorafenib