The Phase 1/2 ACCEPT Trial: Concurrent Cetuximab and Intensity Modulated Radiation Therapy with Carbon Ion Boost for Adenoid Cystic Carcinoma of the Head and Neck

Int J Radiat Oncol Biol Phys. 2020 Jan 1;106(1):167-173. doi: 10.1016/j.ijrobp.2019.09.036. Epub 2019 Oct 3.


Purpose: The adenoid cystic carcinoma (ACC), Erbitux, and Particle Therapy (ACCEPT) phase 1/2 trial (NCT01192087) evaluated a combined-modality approach (concurrent cetuximab and intensity modulated radiation therapy with carbon ion boost) for newly diagnosed nonmetastatic head and neck ACC.

Methods and materials: Twenty-three patients with ACC were enrolled between June 2012 and June 2017 after initial diagnosis or postoperatively. All received a 400 mg/m2 cetuximab loading dose a week before radiation therapy, followed by weekly 250 mg/m2 doses starting on the first day of radiation therapy. The carbon ion radiation therapy boost was 24 Gy (relative biological effectiveness) in 8 daily fractions, followed by intensity modulated radiation therapy (54 Gy). The primary endpoint was safety and feasibility (defined based on Common Terminology Criteria for Adverse Events grade ≥3 events). Secondary endpoints included local and distant relapse, disease-free survival, and overall survival.

Results: Disease was most commonly in the paranasal sinuses (30%), palate (17%), and nasopharynx (17%). Nine (39%) patients underwent surgery (R1: 22%, R2: 78%). Median follow-up was 38.5 months. No patients experienced grade 4 to 5 events. Rates of grade 3 rash and radiation dermatitis were 17% and 22%, respectively. Grade 2 and 3 mucositis and dysgeusia occurred in 43% and 48% and in 9% and 0%, respectively. Grade 2 to 3 dysphagia and xerostomia were present in 43% and 4% and in 26% and 0%, respectively. At last follow-up, 5 (22%) patients experienced in-field relapse and 6 (26%) developed distant metastases. The 3-year disease-free survival was 67%, and median overall survival was 54 months.

Conclusions: Outcomes of this trial were satisfactory. Although the trial did not meet the predefined criteria of feasibility owing to the comparatively high rates of grade 3 dermatitis, numbers are comparable to existing data on cetuximab + radiation therapy.

Publication types

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

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Carcinoma, Adenoid Cystic / pathology
  • Carcinoma, Adenoid Cystic / therapy*
  • Cetuximab / administration & dosage
  • Cetuximab / therapeutic use*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Combined Modality Therapy / methods
  • Deglutition Disorders / etiology
  • Disease-Free Survival
  • Dose Fractionation, Radiation
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Heavy Ion Radiotherapy* / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Radiodermatitis / etiology
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Relative Biological Effectiveness
  • Xerostomia / etiology


  • Antineoplastic Agents, Immunological
  • Cetuximab

Associated data