A phase 2 study of pemetrexed plus gemcitabine every 2 weeks for patients with recurrent or metastatic head and neck squamous cell cancer

Cancer. 2011 Feb 15;117(4):795-801. doi: 10.1002/cncr.25464. Epub 2010 Oct 4.


Background: Preclinical studies suggest that additive or synergistic effects are achieved with the combination of pemetrexed plus gemcitabine. A phase 1 study of pemetrexed plus gemcitabine given every 2 weeks demonstrated encouraging preliminary efficacy against head and neck squamous cell cancer (HNSCC).

Methods: This was an open-label, single-institution, single-arm, phase 2 study for patients who had received no more than 2 cytotoxic regimens for recurrent and/or metastatic HNSCC. All patients received pemetrexed 500 mg/m² intravenously plus gemcitabine 1250 mg/m² intravenously every 2 weeks with vitamin B12 and folate support. The primary endpoint was the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST); secondary endpoints were to estimate overall survival and to evaluate safety and tolerability.

Results: Twenty-five patients received therapy. All patients had received prior radiotherapy, and half had received prior cytotoxic chemotherapy for recurrent and/or metastatic disease. Neutropenia (grade ≥ 3) occurred in 24% of patients. Four patients (16%) had a partial response (PR) according to RECIST, and 5 additional patients (20%) had objective tumor reductions of > 20 but < 30% did not meet RECIST criteria for a PR. The median overall survival for all treated patients was 8.8 months.

Conclusions: Treatment with pemetrexed plus gemcitabine every 2 weeks with vitamin support generally was well tolerated. The results of this study provided further evidence that pemetrexed may have significant palliative activity against advanced HNSCC.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / drug therapy
  • Carcinoma / mortality
  • Carcinoma, Squamous Cell
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Female
  • Glutamates / administration & dosage*
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / mortality
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms, Squamous Cell / drug therapy
  • Neoplasms, Squamous Cell / mortality
  • Pemetrexed
  • Recurrence
  • Squamous Cell Carcinoma of Head and Neck


  • Glutamates
  • Pemetrexed
  • Deoxycytidine
  • Guanine
  • gemcitabine