Phase 2 trial of oxaliplatin and pemetrexed as an induction regimen in locally advanced head and neck cancer

Cancer. 2012 Feb 15;118(4):1007-13. doi: 10.1002/cncr.26364. Epub 2011 Jul 15.

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Drug Therapy, Combination
  • Female
  • Glutamates / adverse effects
  • Glutamates / therapeutic use*
  • Guanine / adverse effects
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / mortality
  • Humans
  • Induction Chemotherapy / methods*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / adverse effects
  • Organoplatinum Compounds / therapeutic use*
  • Outcome Assessment, Health Care
  • Oxaliplatin
  • Pemetrexed
  • Severity of Illness Index*
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Glutamates
  • Organoplatinum Compounds
  • Pemetrexed
  • Oxaliplatin
  • Guanine