Cetuximab and platinum-based chemoradio- or chemotherapy of patients with epidermal growth factor receptor expressing adenoid cystic carcinoma: a phase II trial

Abstract

Background:Epidermal growth factor receptor (EGFR) is highly expressed in adenoid cystic carcinoma (ACC). The efficacy and toxicity of cetuximab with concomitant platinum-based chemoradio- or chemotherapy in patients with locally advanced or metastatic ACC, respectively, was evaluated.Methods:Eligible patients (9 with locally advanced tumour and 12 with metastases) had positive tumour EGFR expression. The cetuximab loading dose (400 mg m−2) was followed by 250 mg m−2 per week. Locally advanced tumours were irradiated (mean dose 65 Gy) and treated with concomitant cisplatin (75 mg m−2, intravenously). Patients with metastases received concomitant cisplatin and 5-fluorouracil (4 × 1000 mg m−2).Results:For patients with locally advanced disease (median follow-up: 52 months), the median progression-free survival (PFS) was 64 months and the 2-year overall survival (OS) rate was 100%. For patients with metastases (median follow-up: 72 months), the median PFS and OS were 13 and 24 months, respectively. In both groups the objective response rate was >40%. Skin rash, in-field dermatitis, mucositis and vomiting were the most frequent grade 3/4 adverse events.Conclusion:In this single-arm study, the efficacy of cetuximab plus chemoradio- or chemotherapy appeared favourable as compared with historical controls. All side effects were manageable and did not hamper the treatment.

Clinical and molecular insights into adenoid cystic carcinoma: Neural crest‐like stemness as a target

“…Gefitinib, the first inhibitor of EGFR's tyrosine kinase domain; Lapatinib, a TKI targeting EGFR and human epidermal growth factor receptor 2 (HER2/neu or ERBB2); and cetuximab, a monoclonal antibody inhibitor of EGFR, each failed to elicit objective responses in ACC patients . Combinatorial therapy using cetuximab as a backbone with cisplatin, and 5‐fluorouracil in 12 patients with metastatic EGFR‐positive ACC or cisplatin, and concomitant radiotherapy in nine patients with locally advanced EGFR‐positive ACC, revealed favorable results compared to historical outcomes. Objective responses were found in four (44%) patients with locally advanced disease and five (42%) patients with metastatic disease .…”

“…Combinatorial therapy using cetuximab as a backbone with cisplatin, and 5‐fluorouracil in 12 patients with metastatic EGFR‐positive ACC or cisplatin, and concomitant radiotherapy in nine patients with locally advanced EGFR‐positive ACC, revealed favorable results compared to historical outcomes. Objective responses were found in four (44%) patients with locally advanced disease and five (42%) patients with metastatic disease . Although the toxicity of these regimens can be high, regimens combining EGFR inhibitors; platinum‐based chemotherapy; and radiotherapy, when indicated, may be a viable treatment approach in ACC.…”

Adenoid cystic carcinoma of the head and neck – An update

“…For an overview of ongoing or planned clinical trials of targeted therapies for AdCC, the reader is referred to the recent publication of Dillon et al [114]. The latest efforts combine cytotoxic and targeted treatments: in patients with EGFR-expressing AdCC, the efficacy of cetuximab plus cisplatin-based chemoradiotherapy (for locally advanced tumors) or chemotherapy (for systemic disease) appeared encouraging and was associated with manageable toxicity [115].…”

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

“…Cetuximab was also tested in conjunction with chemotherapy (radiation and cisplatin for local disease, cisplatin +5‐fluorouracil for metastatic disease), which reported a >40% objective response rate. The median progression‐free survival (PFS) was 64 months and the overall survival rate was 100% for localized disease, whereas median PFS was 13 months and the overall survival was 24 months 72. Agulnik et al73 conducted a phase II trial for patients whose tumors expressed EGFR and/or HER‐2.…”