Methotrexate plus or minus cetuximab as first-line treatment in a recurrent or metastatic (R/M) squamous cell carcinoma population of the head and neck (SCCHN), unfit for cisplatin combination treatment, a phase Ib-randomized phase II study Commence

Head Neck. 2020 May;42(5):828-838. doi: 10.1002/hed.26053. Epub 2020 Jan 6.

Abstract

Background: Methotrexate in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) has limited progression-free survival (PFS) benefit. We hypothesized that adding cetuximab to methotrexate improves PFS.

Methods: In the phase-Ib-study, patients with R/M SCCHN received methotrexate and cetuximab as first-line treatment. The primary objective was feasibility. In the phase-II-study patients were randomized to this combination or methotrexate alone (2:1). The primary endpoint was PFS. Secondary endpoints were overall survival (OS), toxicity, and quality of life (QoL).

Results: In six patients in the phase-Ib-study, no dose limiting toxicities were observed. In the phase II study, 30 patients received the combination and 15 patients methotrexate. In the phase-II-study median PFS was 4.5 months in the combination group vs 2.0 months in the methotrexate group (HR 0.37; P = .002). OS, toxicity, and QoL were not significantly different.

Conclusion: Cetuximab with methotrexate improved PFS without increased toxicity in R/M SCCHN-patients.

Keywords: cetuximab; first-line; methotrexate; palliative treatment; recurrent or metastatic squamous cell carcinoma of the head and neck.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Squamous Cell* / drug therapy
  • Cetuximab / therapeutic use
  • Cisplatin / therapeutic use
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Methotrexate / therapeutic use
  • Neoplasm Recurrence, Local / drug therapy
  • Quality of Life
  • Squamous Cell Carcinoma of Head and Neck / drug therapy

Substances

  • Cetuximab
  • Cisplatin
  • Methotrexate