Gefitinib (ZD1839, Iressa™) as palliative treatment in recurrent or metastatic head and neck cancer

Abstract

To assess the level of activity and toxicity of gefitinib (ZD1839, Iressat) in a population of patients with locally recurrent and/or metastatic head and neck cancer. Patients were recruited into an expanded access programme through the multidisciplinary head and neck clinics at the Royal Marsden and St George's Hospitals. Patients were required to have received at least one course of standard systemic chemotherapy or radiation therapy, or be medically unfit for chemotherapy. Patients were commenced on single-agent gefitinib at a dose of 500 mg day À1 . Clinical, symptomatic and radiological response, time to progression (TTP), survival and toxicity were recorded. A total of 47 patients were enrolled (35 male and 12 female) with a median age of 62 years (range 18 -93 years). The observed clinical response rate was 8% with a disease control rate (complete response, partial response, stable disease) of 36%. In all, 34% of patients experienced an improvement in their symptoms. The median TTP and survival were 2.6 and 4.3 months, respectively. Acneiform folliculitis was the most frequent toxicity observed (76%) but the majority of cases were grade 1 or 2. Only four patients experienced grade 3 toxicity of any type (all cases of folliculitis). Gefitinib was well tolerated and yielded symptomatic improvement in one-third of patients. However, this agent appeared to possess limited antitumour activity in this group of patients with head and neck cancer in whom the objective response rate, median TTP and survival were all lower than has been reported in a previous study.

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

“…The median TTP and OS were 2.6 and 4.3 months, respectively. Acneiform folliculitis was the most frequent toxicity observed (76%) (Kirby et al, 2006). In another phase II trial with gefitinib (250 mg day À1 ) in 70 SCCHN patients, two PRs and a 34% DCR were observed.…”

Dual EGFR and mTOR targeting in squamous cell carcinoma models, and development of early markers of efficacy

“…The epidermal growth factor receptor (EGFR) is a validated target in SCC of the head and neck (Bonner et al, 2006). Erlotinib (Tarceva; OSI Pharmaceuticals, Uniondale, NY, USA) and gefitinib (Iressa; Astrazeneca Inc., Willmington, DL, USA) are quinazoline derivatives that reversibly inhibit the tyrosine kinase (TK) of EGFR, showing in vitro and in vivo activity in SCCHN cell lines (Amador et al, 2004;Jimeno et al, 2006) as well as in phase II clinical trials (Soulieres et al, 2004;Kirby et al, 2006). Tumour responses induced by these agents are, however, infrequent and transient and even sensitive patients rapidly develop secondary resistance.…”

Novel Chemoradiotherapy Regimens Incorporating Targeted Therapies in Locally Advanced Head and Neck Cancers

“…Gefitinib is an oral EGFR-TKI with modest single-agent activity in recurrent or metastatic HNSCC (Cohen et al, 2003;Cohen et al, 2005;Kirby et al, 2006). However, 2 phase III randomized trials did not show survival benefit of single-agent gefitinib over standard methotrexate (Stewart et al, 2009) or of docetaxel plus gefitinib versus docetaxel plus placebo in patients with recurrent or metastatic HNSCC (Argiris et al, 2009).…”