Phase II Trial of ZD1839 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Abstract

ZD1839 has single-agent activity and is well tolerated in refractory SCCHN. In contrast to other reports, development of skin toxicity was a statistically significant predictor of response and improved outcome.

Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies

“…However, skin may still be an effective pharmacodynamic surrogate for EGFR targeted drug activity. Other studies correlated the occurrence and the grade of the skin rash after HER-kinase therapies with clinical outcome, but again this concordance was not present in all studies (Baselga, 2003;Clark et al, 2003;Cohen et al, 2003;Saltz et al, 2003;van Zandwijk, 2003). Here, we provide a potential molecular explanation for this discrepancy.…”

“…Although the reason for this discrepancy is unknown, the occurrence of skin rash has been of particular clinical relevance since several studies have correlated it with antitumour activity (Cohen et al, 2003;Saltz et al, 2003;Perez-Soler et al, 2004).…”

“…Several clinical studies have shown a positive correlation of the incidence of skin rash and tumour response or survival (Baselga, 2003;Clark et al, 2003;Cohen et al, 2003;Perez-Soler, 2003;Saltz et al, 2003;PerezSoler et al, 2004;Soulieres et al, 2004). However, other studies have failed to observe this correlation .…”

Gefitinib (‘Iressa’, ZD1839) and new epidermal growth factor receptor inhibitors

“…Existing treatments improve survival times, but many patients with advanced disease relapse and require further therapy to palliate symptoms and improve survival. This highlights the significant unmet need for novel, targeted agents (Herbst and Kies, 2002;O'Dwyer and Benson, 2002;Herbst and Langer, 2002;Cohen, 2003;Cohen et al, 2003a). …”

“…This compares with median survival times of 6 -8 months from Phase III trials of other agents in this setting. Skin toxicities, never greater than grade 2, were observed in 48% of patients, and diarrhoea was observed in 50% of patients (at grade 3 in three patients) (Cohen et al, 2003a). A Phase II trial is recruiting patients (n ¼ 63) with recurrent SCCHN to investigate gefitinib monotherapy (250 mg day À1 ).…”