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Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer†‡
Final results of a randomized, double-blind, placebo-controlled, phase 3 study
Article first published online: 20 MAR 2012
Copyright © 2012 American Cancer Society
Volume 118, Issue 19, pages 4694–4705, 1 October 2012
How to Cite
Urba, S., van Herpen, C. M. L., Sahoo, T. P., Shin, D. M., Licitra, L., Mezei, K., Reuter, C., Hitt, R., Russo, F., Chang, S.-C., Hossain, A. M., Frimodt-Moller, B., Koustenis, A. and Hong, R.-L. (2012), Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer. Cancer, 118: 4694–4705. doi: 10.1002/cncr.27449
Some of the results of this study have been previously disclosed at the European Society for Medical Oncology Congress; October 8-12, 2010; Milan, Italy.
Registry name: ClinicalTrials.gov; registry identifier number: NCT00415194; registry URL: http://clinicaltrials.gov/ct2/show/NCT00415194?term=head+neck+cancer+pemetrexed+cisplatin&rank=1
- Issue published online: 19 SEP 2012
- Article first published online: 20 MAR 2012
- Manuscript Accepted: 27 DEC 2011
- Manuscript Revised: 16 NOV 2011
- Manuscript Received: 19 JUL 2011
- head and neck cancer;
- clinical trial;
- phase 3
Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN.
In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2; n = 398) or placebo plus cisplatin (75 mg/m2; n = 397) to assess overall survival (OS) and secondary endpoints.
Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P = .082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors.
Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers. Cancer 2012. © 2012 American Cancer Society.