title: Phase I trial of radiation therapy and sorafenib in unresectable liver metastases.
abstract: To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases.
  
  
  
  Eligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I - SBRT: effective liver volume irradiated (Veff)<80% (30-60Gy in 6 fractions); II - WLRT: Veff>80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2-3, was delivered at 3 escalating dose levels (200-400mg twice daily). Dose limiting toxicity was defined as any grade 3+ liver toxicity, or grade 4+ treatment-related toxicity.
  
  
  
  Thirty-three patients were treated: 18 in stratum I (median dose 42Gy), 15 in stratum II. The MTD was not reached. Grade 3+ toxicity was seen in 33% of patients, at a median of 10days. Two deaths from non-classic liver toxicity occurred post WLRT in stratum II. The median overall survival was 22.3 and 5.7months for strata I and II respectively.
  
  
  
  Sorafenib and 21.6Gy in 6 fraction WLRT resulted in unacceptably high rates of liver toxicity. Although sorafenib combined with SBRT was tolerable, the observed efficacy does not merit further clinical evaluation.
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Goody
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Brade
authors.affiliation: Department of Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiation Physics, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Tim
authors.initials: T
authors.lastname: Craig
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Brierley
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Dinniwell
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Rebecca K S
authors.initials: RKS
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada; Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Cho
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada; Department of Radiation Oncology, Stronach Regional Cancer Centre, Newmarket, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kassam
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Jolie
authors.initials: J
authors.lastname: Ringash
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Canada. Electronic address: Laura.Dawson@rmp.uhn.on.ca.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Dawson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D059248:Chemoradiotherapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008099:Liver / Q000528:radiation effects; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D016634:Radiosurgery / Q000009:adverse effects; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Liver metastases; Radiotherapy; Sorafenib