Preliminary results of HKNPC-1001 trial to evaluate the role of induction TPF followed by weekly docetaxel and cetuximab in combination with intensity modulated radiotherapy for locally recurrent nasopharyngeal carcinoma

Aim/Background

This phase II trial aims to study the efficacy of using induction TPF chemotherapy (docetaxel, cisplatin and fluorouracil) for 3 cycles followed by weekly docetaxel and cetuximab in concurrence with Intensity Modulated Radiotherapy (IMRT) re-irradiation in patients with advanced locoregional recurrent nasopharyngeal carcinoma (NPC).

Methods

We aim to enroll 45 patients with recurrent NPC (T3 – T4, N0 – N1, M0) to be treated with TPF induction chemotherapy (docetaxel 75 mg/m² D1, cisplatin 75 mg/m² D1, fluorouracil 750 mg/m² D1-D4) every 3 weeks for 3 cycles, followed by weekly docetaxel (15 mg/m²) and cetuximab (400 mg/m² in initial dose, then 250 mg/m² in subsequent doses) for 7 weeks in concurrence with IMRT (60Gy over 30 fractions, 5 fractions per week). So far, 32 patients have been recruited: 26 patients had completed the treatment, 1 died and 5 patients withdrew from study after 1 cycle of TPF. The median follow-up period was 19 months.

Results

The local progression free rate at 2 years was 74.2%. The 2 year overall survival was 66.8%. The most frequently reported acute side effects (≥grade 3) in TPF induction phase were neutropenia (37.5%) and hyponatremia (28.1%) and 5 patients withdrew after the first cycle of TPF due mostly to fatigue. During IMRT, the most common acute side effect (≥grade 3) was mucositis (23.0%). So far, 12.5% patients had died of cancer. Temporal lobe necrosis (TLN) developed in 8 cases and 5 patients died due to treatment related complications (2 epistaxis, 1 TLN, 1 sudden death after cycle 1 TPF and 1 chest infection after completion of whole course of treatment).

Conclusions

In this preliminary analysis, induction TPF appears to be poorly tolerated. Promising early local control and survival rates achieved after intensive chemo-re-irradiation should be carefully weighed against the occurrence of potentially lethal early toxicities and late complications.

Clinical trial identification

NCT01326559

Disclosure

All authors have declared no conflicts of interest.