Phase I study of panitumumab + chemoradiotherapy (CRT) for head and neck cancer (HNC)

Abstract

6007 Background: Both chemotherapy and epidermal growth factor receptor (EGFR) antibody therapy improve outcomes in HNC when added to radiotherapy. This phase I study adds the fully human anti-EGFR antibody, panitumumab, to carboplatin/paclitaxel/IMRT for HNC. Methods: Nineteen treatment-naïve adults with stage III/IV HNC (1° sites: oropharynx, hypopharynx and unknown primary) with normal hematologic, renal, and liver function enrolled in a phase I study to determine the maximum tolerated dose (MTD) of paclitaxel in 2 dose levels (DLs) (15 and 30 mg/m2 wkly x 7 wks) with fixed-dose carboplatin and panitumumab (AUC of 1.5 and 2.5 mg/kg wkly, respectively) plus IMRT (70 Gy). All patients (pts) received a gastrostomy (g-) tube. Pts were enrolled in sets of 3, with an expansion cohort of 10 at the MTD. Acute toxicities were graded per Common Toxicities Criteria for Adverse Events v3.0. Chronic toxicities occurring ≥ 16 wks post treatment were graded per RTOG/EORTC Late Radiation Morbidity Scoring Scheme. Results: Three pts were treated in DL 1, and 16 in DL 2 (10 of these in the expansion cohort). All are evaluable for acute toxicities; 13 pts are evaluable for chronic toxicities. One dose-limiting toxicity (DLT) occurred in DL 2: grade (gr) 4 febrile neutropenia. One pt had a gr 4 sepsis and thromboembolic event, not considered a DLT as it occurred 3 wks after treatment. Other adverse events include gr 3 dysphagia (n=18, 95%), gr 3/4 mucositis (n=17, 89%), gr 2/3 acneiform rash (n=15, 79%), gr 3 radiation dermatitis (n=7, 37%), and gr 3 nausea (n=3, 16%). Neither dose-reduction nor radiotherapy breaks > 3 days were necessary. Chemotherapy and panitumumab were held for 1–2 wks in 3 pts in DL 2 for gr 4 mucositis (n=2) and gr 3 mucositis and nausea (n=1). There were no gr 3/4 chronic toxicities. Median duration of g-tube use was 10 wks. Of 15 pts evaluable for response, 13 (87%) had complete response, 1 had 1 positive node on neck dissection, and 1 has a residual base of tongue mass on restaging CT (further evaluation pending). Conclusions: Panitumumab added to CRT for HNC treatment is safe and feasible. The MTD is defined as the study's DL2. Early results suggest that panitumumab + CRT is a highly effective regimen for HNC. Phase II study is warranted. No significant financial relationships to disclose.