title: Phase I study of pemetrexed with sorafenib in advanced solid tumors.
abstract: To determine if combination treatment with pemetrexed and sorafenib is safe and tolerable in patients with advanced solid tumors.
  
  
  
  Thirty-seven patients were enrolled and 36 patients were treated (24 in cohort A; 12 in cohort B). The cohort A dose schedule resulted in problematic cumulative toxicity, while the cohort B dose schedule was found to be more tolerable. The maximum tolerated dose (MTD) was pemetrexed 750 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1-5. Because dosing delays and modifications were associated with the MTD, the recommended phase II dose was declared to be pemetrexed 500 mg/m2 every 14 days with oral sorafenib 400 mg given twice daily on days 1-5. Thirty-three patients were evaluated for antitumor activity. One complete response and 4 partial responses were observed (15% overall response rate). Stable disease was seen in 15 patients (45%). Four patients had a continued response at 6 months, including 2 of 5 patients with triple-negative breast cancer.
  
  
  
  A phase I trial employing a standard 3 + 3 design was conducted in patients with advanced solid tumors. Cohort A involved a novel dose escalation schema exploring doses of pemetrexed every 14 days with continuous sorafenib. Cohort B involved a modified schedule of sorafenib dosing on days 1-5 of each 14-day pemetrexed cycle. Radiographic assessments were conducted every 8 weeks.
  
  
  
  Pemetrexed and intermittent sorafenib therapy is a safe and tolerable combination for patients, with promising activity seen in patients with breast cancer.
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Poklepovic
authors.affiliation: Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Shafer
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.|Current address: Department of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Roberts
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.|Current address: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Prithviraj
authors.initials: P
authors.lastname: Bose
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: McGuire
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Tombes
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Shrader
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Strickler
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Quigley
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Biostatistics, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Wan
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kmieciak
authors.affiliation: Departments of Pathology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: H Davis
authors.initials: HD
authors.lastname: Massey
authors.affiliation: Departments of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Booth
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Moran
authors.affiliation: Departments of Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.|Departments of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Dent
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D000068437:Pemetrexed / Q000008:administration & dosage*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D000077157:Sorafenib; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D000068437:Pemetrexed; D009536:Niacinamide; D000077157:Sorafenib; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: clinical trial; pemetrexed; solid tumors; sorafenib