Preliminary results of a phase II study to evaluate gefitinib combined with docetaxel and cisplatin in patients with recurrent and/or metastatic squamous-cell carcinoma of the head and neck

Abstract

5563 Background: Docetaxel and cisplatin (D/C) [75 mg/m2 each iv] combination therapy for squamous-cell carcinoma of the head and neck (SCCHN) yields response rates (RRs) of 30–40% and is relatively well tolerated. This study has evaluated the combination of gefitinib (IRESSA) and D/C in patients (pts) with SCCHN. Methods: Pts with histologically confirmed recurrent and/or metastatic SCCHN (≥1 unidimensionally measurable lesion by RECIST, WHO performance status (PS) <2, aged <70 years) received gefitinib 250 mg/day and D/C (75 mg/m2 each iv, every 3 weeks; maximum 6 cycles). Pts with clinical benefit continued gefitinib following completion of combination therapy. Neoadjuvant pretreatment with C-based chemotherapy ≥6 months previously or prior radiotherapy was allowed. Adverse events (AEs) were assessed by NCI-CTC (V3). Results: To date, 17/23 enrolled pts are eligible: median age, 55 years (range 31–69); male/female, 15/2; WHO PS 0/1, 11/6; metastatic sites 1/2–3/>3, 9/3/5 (38.8% lesions); median number D/C cycles, 4 (range 1–6); median duration gefitinib treatment, 71 days (range 7–244). 16/17 pts were evaluable for efficacy: 6 (37.5%) complete responses (CR) and 4 (25.0%) partial responses (PR), giving an RR of 62.5% (95% CI 35.4–84.8). Disease control rate (DCR) [CR + PR + stable disease] was 75% (95% CI 47.6–92.7). Median progression-free survival (PFS) was 5.1 months (95% CI 2.0–7.1). All 17 pts were assessed for safety. Grade 3/4 AEs were: neutropenia, 41.2% (including febrile neutropenia, 23.5%); anemia, 17.7% (secondary to D/C; 1 withdrawal); asthenia, 11.8%; diarrhea, vomiting, anorexia, and leukopenia, all 5.9%. Pts with ≥1 dose reduction: 52.9% (D), 58.8% (C). One pt died (septic shock/febrile neutropenia) 1 week after start of therapy. Conclusions: Gefitinib in combination with D/C has demonstrated encouraging RR and DCR in SCCHN. PFS of 5.1 months is interesting given that the overall survival of pts with recurrent and/or metastatic SCCHN is usually 6 months. The triplet combination did not cause more hematologic AEs than would be expected using D/C alone. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca