Phase 1 trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer

Abstract

BACKGROUND: Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase‐2 (COX‐2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen. METHODS: Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended. RESULTS: The recommended phase 2 dose of celecoxib was 400 mg. Three dose‐limiting toxicities included late in‐field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow‐up of 11 months, the 1‐year locoregional control, progression‐free survival, and overall survival rates were 60%, 37%, and 55%, respectively. CONCLUSIONS: Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis. Cancer 2011. © 2011 American Cancer Society.

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

“…In addition to the above work, preclinical findings and a Phase I clinical trial suggest celecoxib could synergistically enhance radiation therapy treatment in prostate, lung and recurrent head and neck cancers [49][50][51] . Radiotherapy (RT) is the primary treatment modality for non-metastatic NPC.…”

Expresión de ciclo-oxigenasa 2 en carcinoma de laringe

“…Se ha reportado un ensayo clínico utilizando drogas que bloquean ciclo-oxigenasa 2 13 . En este protocolo se reclutaron 14 pacientes portadores de cáncer de cabeza y cuello previamente irradiados que no eran candidatos para radio quimioterapia concomitante.…”

Evaluation of the Celecoxib Effect against Radiotherapy Induced Acute Toxicities in the Patients with Prostate Cancer Compared with Placebo Group

“…A trial by Johnny Kao et al demonstrated that the concurrent administration of erlotinib, celecoxib at escalated doses (200,400,600 mg twice daily), and reirradiation for a population of patients with recurrent head and neck cancer is an active regimen and safe administration (51).…”