title: A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.
abstract: BACKGROUND
  Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC).
  
  
  METHODS
  This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles.
  
  
  RESULTS
  Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy.
  
  
  CONCLUSIONS
  Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), 300 E 66th Street, New York, NY, 10065, USA, hoa@mskcc.org.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Ho
authors.forename: Brynna L
authors.initials: BL
authors.lastname: Lipson
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Sherman
authors.forename: Han
authors.initials: H
authors.lastname: Xiao
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Fury
authors.forename: Arlyn
authors.initials: A
authors.lastname: Apollo
authors.forename: Nagashree
authors.initials: N
authors.lastname: Seetharamu
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Sofia
authors.initials: S
authors.lastname: Haque
authors.forename: John K
authors.initials: JK
authors.lastname: Lyo
authors.forename: Roberta
authors.initials: R
authors.lastname: Sales
authors.forename: Lisa
authors.initials: L
authors.lastname: Cox
authors.forename: David G
authors.initials: DG
authors.lastname: Pfister
mesh_terms: D000328:Adult; D000368:Aged; D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005493:Folic Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D000077195:Squamous Cell Carcinoma of Head and Neck; D014805:Vitamin B 12 / Q000008:administration & dosage*; D014803:Vitamin B Complex / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D005493:Folic Acid Antagonists; D014803:Vitamin B Complex; D005492:Folic Acid; D000630:Aminopterin; D014805:Vitamin B 12