title: Phase II trial of pemetrexed and bevacizumab in patients with recurrent or metastatic head and neck cancer.
abstract: OBJECTIVE
  We hypothesized that bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), will potentiate the activity of pemetrexed, a multitargeted antifolate, in squamous cell carcinoma of the head and neck (SCCHN).
  
  
  METHODS
  Patients with previously untreated, recurrent, or metastatic SCCHN were treated with pemetrexed 500 mg/m(2) and bevacizumab 15 mg/kg given intravenously every 21 days with folic acid and B(12) supplementation until disease progression. Primary end point was time-to-progression (TTP). DNA was isolated from whole blood samples for the detection of polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase (MTHFR), and VEGF.
  
  
  RESULTS
  Forty patients were enrolled. The median TTP was 5 months, and the median overall survival (OS) was 11.3 months. In 37 evaluable patients, the overall response rate was 30%, including a complete response rate of 5%, and the disease control rate was 86%. Grade 3 to 5 bleeding events occurred in six patients (15%): four were grade 3, and two were fatal. Other serious toxicities in 10% or more of patients included neutropenia (10%) and infection (12.5%). One patient died of sepsis after receiving eight cycles of therapy. For the MTHFR A1298C (rs1801131) single nucleotide polymorphisms, homozygote patients with AA had worse OS (P = .034).
  
  
  CONCLUSIONS
  The addition of bevacizumab to pemetrexed resulted in promising efficacy outcomes in SCCHN. Bleeding events were frequent but some may have been due to natural history of disease. Polymorphisms in MTHFR may offer potential for treatment individualization.
authors.affiliation: Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA. argirisae@upmc.edu
authors.forename: Athanassios
authors.initials: A
authors.lastname: Argiris
authors.forename: Michalis V
authors.initials: MV
authors.lastname: Karamouzis
authors.forename: William E
authors.initials: WE
authors.lastname: Gooding
authors.forename: Barton F
authors.initials: BF
authors.lastname: Branstetter
authors.forename: Shilong
authors.initials: S
authors.lastname: Zhong
authors.forename: Luis E
authors.initials: LE
authors.lastname: Raez
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Savvides
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068437:Pemetrexed; D011110:Polymorphism, Genetic / Q000235:genetics; D012074:Remission Induction; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005971:Glutamates; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068437:Pemetrexed; D000068258:Bevacizumab; D006147:Guanine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase