Phase I trial of pemetrexed in combination with cetuximab and concurrent radiotherapy in patients with head and neck cancer

A. Argiris, M. V. Karamouzis, R. Smith, A. Kotsakis, M. K. Gibson, S. Y. Lai, S. Kim, B. F. Branstetter, Y. Shuai, M. Romkes, L. Wang, J. R. Grandis, R. L. Ferris, J. T. Johnson, D. E. Heron

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background: We studied the combination of pemetrexed, a multi-targeted antifolate, and cetuximab, an mAb against the epidermal growth factor receptor, with radiotherapy in poor prognosis head and neck cancer. Patients and methods: Patients received pemetrexed on days 1, 22, and 43 on a dose-escalation scheme with starting level (0) 350 mg/m 2 (level -1, 200 mg/m 2; level +1, 500 mg/m 2) with concurrent radiotherapy (2 Gy/day) and cetuximab in two separate cohorts, not previously irradiated (A) and previously irradiated (B), who received 70 and 60-66 Gy, respectively. Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated. Results: Thirty-two patients were enrolled. The maximum tolerated dose of pemetrexed was 500 mg/m 2 in cohort A and 350 mg/m 2 in cohort B. Prophylactic antibiotics were required. In cohort A, two dose-limiting toxicities (DLTs) occurred (febrile neutropenia), one each at levels 0 and +1. In cohort B, two DLTs occurred at level +1 (febrile neutropenia; death from perforated duodenal ulcer and sepsis). Grade 3 mucositis was common. No association of gene polymorphisms with toxicity or efficacy was evident. Conclusion: The addition of pemetrexed 500 mg/m 2 to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients.

Original languageEnglish (US)
Pages (from-to)2482-2488
Number of pages7
JournalAnnals of Oncology
Volume22
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Cetuximab
  • Head and neck cancer
  • Pemetrexed
  • Radiotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

Fingerprint Dive into the research topics of 'Phase I trial of pemetrexed in combination with cetuximab and concurrent radiotherapy in patients with head and neck cancer'. Together they form a unique fingerprint.

Cite this