title: Cutaneous side effects of combined therapy with sorafenib and pegylated interferon alpha-2b in metastatic melanoma (phase II DeCOG trial).
abstract: OBJECTIVE
  During a clinical study with combined therapy of sorafenib and pegylated interferon alpha-2b (SoraPeg study) of the German Dermatologic Oncology Group (ADO/DeCOG), multiple and severe cutaneous side effects were observed. This study sought to analyze these cutaneous side effects, particularly because future studies with combinations of interferon alpha and targeted therapies are planned.
  
  
  METHODS
  In a multicenter phase-II-DeCOG study (NCT00623402) in 10 dermato-oncology centers, 55 patients with metastatic melanoma received a combination of sorafenib (2 x 400 mg/day orally) and pegylated interferon alpha-2b (3 μg/kg body weight 1 x/week subcutaneously). All cutaneous side effects were documented.
  
  
  RESULTS
  Forty-one patients (74.5 %) developed cutaneous side effects, particularly exanthems (51.2 %), hand-foot syndrome (36.5 %), alopecia (36.5 %) and pruritus (24.4 %). Due to the cutaneous side effects, dose reductions were required in 10 patients, interruption of therapy in 10 cases and permanent discontinuation of therapy and in one patient with extensive follicular-cystic lesions. Exanthems were seen more frequently in women (76.2 %) than in men (23.8 %). The occurrence of cutaneous side effects was not correlated with clinical outcome or prognosis.
  
  
  CONCLUSIONS
  The combination of sorafenib/pegylated interferon alpha-2b caused more cutaneous side effects than have been reported for single agents. Despite intensive dermatologic management of the cutaneous side effects 24 % of patients required a dose modification.
authors.affiliation: Department of Dermatology and Allergology, Hannover Medical School, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Degen
authors.forename: Michael
authors.initials: M
authors.lastname: Weichenthal
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.forename: Uwe
authors.initials: U
authors.lastname: Trefzer
authors.forename: Katharina
authors.initials: K
authors.lastname: Kilian
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Friederike
authors.initials: F
authors.lastname: Egberts
authors.forename: Lìdia Marilia
authors.initials: LM
authors.lastname: Poppe
authors.forename: Axel
authors.initials: A
authors.lastname: Hauschild
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015984:Causality; D015897:Comorbidity; D003875:Drug Eruptions / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary*; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D015995:Prevalence; D011994:Recombinant Proteins / Q000008:administration & dosage; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011994:Recombinant Proteins; D009536:Niacinamide; D011092:Polyethylene Glycols; D000077157:Sorafenib; C100416:peginterferon alfa-2a