A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) with correlation using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)

Abstract

6055 Background: Based on the activity of cetuximab + platinum in recurrent NPC (Chan AT et al J Clin Oncol 2005;23: 3568–76), we evaluated the feasibility of adding cetuximab to concurrent cisplatin-IMRT in the curative setting. The effect of cetuximab on DCE-MRI parameters in primary NPC was also studied. Methods: Patients (pts) with untreated, non-metastatic advanced NPC were given an initial dose of i.v. cetuximab (400mg/m2) followed by IMRT (74Gy) 7–10 days later. RT was delivered concurrently with weekly i.v. cetuximab (250mg/m2) and i.v. cisplatin (30mg/m2) over 6–7 weeks. DCE-MRI was conducted before RT at baseline and 1 week after the first cetuximab dose. Results: Twenty pts (mean age 42 years, range 24–59, 17 males) were enrolled and evaluated for acute toxicity (NCI CTCAE v3.0) (n=20) and response (n=12). Stage distribution at baseline was: T1–2b = 6 pts (30%); T3–4 = 14 pts (70%); N0–1 = 11 pts (55%); N2–3 = 9 pts (45%); AJCC stage III = 12 pts (60%), IVa = 7 pts (35%), IVb = 1pt (5%). All pts completed IMRT without major interruptions. Drug compliance was good with 90% of pts completing ≥5 doses of cetuximab, and 80% completing >5 doses of cisplatin. The most common non-hematological grade 3–4 toxicities were RT-mucositis (85%), mouth pain (85%) and dysphagia (45%). Rash was grade 1–2 in 14 pts, grade 3 in 3 pts. Seven pts (35%) required nasogastric tube feeding and 4 pts had grade 3 RT-dermatitis. Grade 3–4 lymphopenia was the commonest hematological toxicity (85%). 6 SAEs were reported due to grade 3 mucositis or dysphagia. At 3 months post-RT, there were 10 (83%) complete responses and 2 partial responses at nasopharynx. All pts were alive at analysis. DCE-MRI performed in 11 pts showed a non-significant rising trend in mean Ktrans (volume transfer coefficient) and initial area under the contrast agent concentration-time curve (AUC). Conclusions: This is the first report on the feasibility of combining cetuximab-cisplatin and IMRT in NPC. Grade 3 mucosal toxicities were common but manageable. Accrual is ongoing and updated DCE-MRI data will be presented. No significant financial relationships to disclose.