Phase II study of 250 mg gefitinib in advanced squamous cell carcinoma of the head and neck (SCCHN)

Abstract

5586 Background: Inhibition of EGFR has demonstrated benefit in SCCHN. Treatment of patients with incurable SCCHN with 500 mg gefitinib PO QD produced an 11% response rate, 53% disease control rate and 29% overall survival at 1 year (JCO 21: 1980, 2003). However better tolerability and equal efficacy to this dose was reported in non-small cell lung cancer patients treated with 250 mg gefitinib . This phase II study of 250 mg gefitinib evaluated activity, toxicity and VEGF levels in patients with advanced SCCHN. Methods: Patients had incurable SCCHN, measurable disease, no prior EGFR-based therapy, ECOG PS ≤ 2, intact organ function, and ability to give informed consent. Patients received gefitinib 250 mg QD PO or via feeding tube. The primary endpoint was objective response rate (CR + PR). Correlative studies included plasma VEGF levels and quality of life measurements using FACT HN Symptom Index score. Results: 65 patients were enrolled from 6/02 to 11/03: 43 men, 22 women; median age 57.5 years; 19 local recurrence only, 22 metastatic only, 24 both. 56 had PS 0 or 1, and 9 had PS 2. All patients had prior radiotherapy; 28 (43%) had prior chemotherapy for recurrent/metastatic disease. 32 (49%) patients received gefitinib via feeding tube. Drug-related toxicity consisted of dermatologic (64%, no grade 3/4), diarrhea (30%, 2 patients with grade 3), and nausea (13%, 1 patient with grade 3). No grade 4 toxicities were observed. 56 patients are evaluable for best response: 2 (3.5%) PR, 19 (34%) SD, and 35 (63%) PD. Mean plasma VEGF levels (Nl < 55 pg/ml) were 162.6 pg/ml pre-therapy and 156.2 pg/ml after 8 weeks. Mean (± S.D.) pre-therapy VEGF level in patients with PR or SD as best response was 113 ± 92 pg/ml compared with 190 ± 357 pg/ml in PD patients (P = 0.26, NSD). Mean quality of life scores were stable: baseline 25.6, 4 weeks 25.9 and 8 weeks 26.36. Conclusions: Gefitinib 250mg QD is well tolerated in advanced SCCHN with modest benefit and without significant deterioration in overall quality of life scores. Plasma VEGF levels were lower in patients with PR or SD compared with PD (NSD) and did not change from baseline after 8 weeks of gefitinib 250 mg. Supported by Astra Zeneca. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis