Phase II study of combination cisplatin, docetaxel and erlotinib in patients with metastatic/recurrent head and neck squamous cell carcinoma (HNSCC)

Abstract

5546 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for advanced or recurrent HNSCC are limited. A recent study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received one regimen of induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75mg/m2 and cisplatin 75mg/m2, intravenously every 3 weeks and erlotinib 150 mg by mouth daily. Results: Nineteen patients have been enrolled thus far. Median age is 54 years (range 45–72). Median ECOG PS is 1 (range 0–2). Thus far, 16 patients are evaluable for response using RECIST criteria. Partial responses have been seen in 14 of 16 patients (confirmed and unconfirmed) including 3 patients who completely regressed in the head and neck region and 2 patients had stable disease. 3 patients have since progressed. One patient had grade 4 febrile neutropenia and 1 patient a grade 3 rash. Otherwise, no other significant grade 3 or 4 toxicities have been reported. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging early activity in advanced HNSCC. Data collection for response rate, duration of response and survival is ongoing. Trial accrual continues up to 50 patients and biopsies are being collected for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). No significant financial relationships to disclose.