title: Phase 2 trial of oxaliplatin and pemetrexed as an induction regimen in locally advanced head and neck cancer.
abstract: BACKGROUND
  This phase 2 trial evaluated the tolerability and clinical efficacy of the combination of oxaliplatin and pemetrexed as an induction chemotherapy regimen in locally advanced head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Forty-two patients were enrolled in the study. Patients received pemetrexed 300 mg/m(2) intravenously (IV) and oxaliplatin 85 mg/m(2) IV every 14 days for a total of 4 cycles. A subset of patients consented to correlative studies including tumor tissue for human papillomavirus (HPV) detection and expression of DNA repair genes that may be predictive of response or resistance to oxaliplatin or pemetrexed.
  
  
  RESULTS
  Response data were available for 40 patients. Eighteen had a partial response, and 1 had a complete response, for a response rate of 47.5%. Patients with HPV(+) disease demonstrated superior response rates, progression-free survival, and overall survival. The regimen was well tolerated, with predominantly grade 1 or 2 alanine aminotransferase/aspartate aminotransferase elevation. One patient had grade 5 toxicity with neutropenia and sepsis. The authors did not identify genes predictive of response or toxicity, although HPV(+) tumors demonstrated a unique gene expression signature.
  
  
  CONCLUSIONS
  Although the response rate of oxaliplatin and pemetrexed proved less than anticipated, the combination remains an active induction regimen in HNSCC. This regimen should be evaluated further in combination with targeted agents, such as cetuximab, especially in the HPV(+) patient population.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6307, USA. Jill.Gilbert@vanderbilt.edu
authors.forename: Jill
authors.initials: J
authors.lastname: Gilbert
authors.forename: Barbara
authors.initials: B
authors.lastname: Murphy
authors.forename: Mary S
authors.initials: MS
authors.lastname: Dietrich
authors.forename: Eve
authors.initials: E
authors.lastname: Henry
authors.forename: Richard
authors.initials: R
authors.lastname: Jordan
authors.forename: Ashley
authors.initials: A
authors.lastname: Counsell
authors.forename: Pamela
authors.initials: P
authors.lastname: Wirth
authors.forename: Wendell G
authors.initials: WG
authors.lastname: Yarbrough
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Slebos
authors.forename: Christine H
authors.initials: CH
authors.lastname: Chung
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005971:Glutamates / Q000009:adverse effects / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D000077150:Oxaliplatin; D000068437:Pemetrexed; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D009944:Organoplatinum Compounds; D000068437:Pemetrexed; D000077150:Oxaliplatin; D006147:Guanine