A Phase I/II Study Of OSI-774 In Combination With Cisplatin In Patients With Recurrent Or Metastatic Squamous Cell Cancer Of The Head And Neck

OBJECTIVES:

• Determine the objective response rate in patients with recurrent or metastatic squamous cell cancer of the head and neck treated with erlotinib and cisplatin.
• Determine the stable disease rates, duration of response, progression-free survival, median survival, and overall survival of patients treated with this regimen.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the relationship between clinical, pharmacokinetic, and pharmacodynamic effects of this regimen in these patients.
• Correlate baseline and post-treatment levels of epidermal growth factor receptor, its downstream signaling components, and markers of angiogenesis and apoptosis in tumor and skin biopsies with clinical outcome in patients treated with this regimen.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral erlotinib once daily on days -6 to 21 for the first course only and cisplatin IV over 60 minutes on day 1. For the second and subsequent courses, patients receive oral erlotinib once daily on days 1-21 and cisplatin as in course 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease after 6 courses may continue to receive erlotinib alone until disease progression.

Cohorts of 3-6 patients receive escalating doses of erlotinib and cisplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.