Cetuximab Plus Concurrent Radiotherapy in Patients With Nasopharyngeal Carcinoma

Discussion

In this study, we assessed the efficacy and safety of BRT without ICT or adjuvant chemotherapy for the treatment of NPC. According to the NCCN guidelines, high-dose CDDP is recommended as a category 1 systemic therapy agent concurrent with RT for SCCHN. For the treatment of advanced NPC, the NCCN states that management of cancer within clinical trials is preferred as the best management strategy among other recommendations, such as ICT followed by CRT/RT or concurrent systemic therapy/RT followed by adjuvant chemotherapy. Optimal therapeutic strategies for advanced NPC are still being sought. CDDP or carboplatin is the agent recommended for use with concurrent RT following ICT or prior to adjuvant chemotherapy; Cmab is not mentioned. However, several reports and meta-analyses have shown comparable efficacy and safety of BRT in the treatment of NPC (5-7, 9-11). In a randomized phase II study in which ICT was administered with docetaxel and CDDP followed by concomitant weekly CDDP (30 mg/m² per week) or Cmab in combination with IMRT for locally advanced NPC, patients in the BRT arm showed better compliance with more oral mucositis, acneiform rash, and dysphagia and comparable OS and disease-free survival (DFS) (11). A single-center retrospective matched case-control study that compared CDDP (25 mg/m² on days 1-3 every 3 weeks) concurrent with IMRT versus Cmab concurrent with IMRT following ICT with TPF for treatment of locally advanced NPC also showed different degrees of toxicity and no statistical differences in OS or DFS (9). Another single-center retrospective study that compared Cmab or NTZ plus IMRT versus high-dose CDDP plus IMRT with or without ICT for stage II to IVb NPC showed comparable results in terms of DFS, locoregional relapse-free survival, distant metastasis-free survival, and OS (7). In the analysis, the occurrence of skin reactions and mucositis were more frequent in patients treated with Cmab or NTZ, but fewer AEs were observed especially with regard to hematologic toxicities, hepatoxicities, nephrotoxicities, and gastrointestinal reactions (7). A meta-analysis that assessed the therapeutic effect of combination treatment with conventional CRT and Cmab compared with conventional CRT showed that patients who accepted additional Cmab treatment could obtain more benefits, such as an increased response rate and prolonged survival (5). Two meta-analyses, both of which included the same six studies comparing Cmab or NTZ concurrent with RT versus CDDP concurrent with RT with or without ICT, showed comparable OS and DFS with fewer hematological and gastrointestinal toxicities and more skin rashes in the Cmab or NTZ group (6, 10). Thus, Cmab is still an option for combination therapy in the treatment of NPC. Baseline clinical data regarding the efficacy and safety of BRT without ICT or adjuvant chemotherapy are essential to establish new combination treatment strategies for NPC.

In the current study, the response rate was high at 86%. All six patients with T1-3 disease achieved a CR regardless of their N status. The only patient who failed to achieve a CR had T4 disease. However, both of the patients with T3 disease developed local recurrence within 1 year. Therefore, none of the patients with ≥T3 disease could be controlled by BRT in this study. In the two above-mentioned case-control studies that provided information on the T classification, the proportion of T3 and T4 disease was 77.0% and 57.2%, respectively (7, 9). In their multivariate analysis of DFS, You et al. (7) showed that the hazard ratio for T3 to T1 tumor stages was 0.93 (95%CI=0.53-1.61; p=0.782). Wu et al. (9) showed that the 5-year OS rate of T3 disease was as high as 80%. The discrepancy between the current study and these previous reports might be attributed to the use of ICT. With regard to AEs, we found that compared with the Bonner trial in which cancers of the oropharynx, hypopharynx, and larynx were eligible (8), the incidence of grade 3 anorexia was higher and the incidences of mucositis and radiation dermatitis were comparable in the present study. Other AEs, such as acneiform rash, weight loss, xerostomia, dysphagia, vomiting, and diarrhea were less common in our study. No serious AEs such as infusion reaction, interstitial pneumonia, or any grade ≥4 toxicity occurred. These findings suggest that BRT can be safely performed in patients with NPC, as for those with SCCHN (12).

In the NCCN guidelines, the TPF regimen is recommended for ICT in the treatment of NPC. TPF chemotherapy causes a high rate of grade 3 or 4 neutropenia and a >10% rate of febrile neutropenia (13). Although CRT with CDDP is the standard treatment regimen for SCCHN, it is associated with high rates of toxicities such as hematotoxicities and nephrotoxicities, especially in combination with TPF ICT (14). BRT has been shown to be associated with different types of AEs compared with CRT, with fewer hematological and renal toxicities (6, 7). Thus, Cmab may be a reasonable alternative to CDDP in terms of AEs in the ICT/RT setting. However, the higher rates of skin rash and mucositis should not be ignored.

The main limitation of our study is that it was a case series without controls. Other limitations are that the sample size was small and that all patients were from a single center.

In this retrospective study, we evaluated the treatment efficacy and toxicities of BRT without ICT or adjuvant chemotherapy in patients with NPC. We found that BRT was tolerable, but the data suggested that ICT or adjuvant chemotherapy is essential at least for ≥T3 disease. Further studies refining existing treatment strategies are needed to establish new standard regimens in patients with NPC.