Response outcome and toxicity after neoadjuvant chemotherapy followed by Intensity Modulated Radiotherapy (IMRT) concurrent with weekly cisplatin in locally advanced nasopharyngeal carcinoma- An Observational Study.

Abstract

BACKGROUND: The treatment of locally advanced nasopharyngeal carcinoma has been very challenging. Currently, CCRT followed by adjuvant chemotherapy is considered as standard. However, the compliance to adjuvant chemotherapy was very poor as shown in different trials. Hence induction chemotherapy followed by local treatment in the form of concurrent chemoradiation seems to be a logical strategy. In our study, we aimed to assess the feasibility of doublet chemotherapy regimen as neoadjuvant chemotherapy followed by CCRT in node positive or LANPC with the purpose of disease shrinkage, more effective and less toxic radiotherapy, decrease in distant metastasis and improved overall survival.

AIMS & OBJECTIVE(S): To assess the effect of neoadjuvant        chemotherapy followed by IMRT concurrent with weekly cisplatin in locally advanced nasopharyngeal carcinoma cases on the toxicity, response outcome and Survival (DFS and OS)

PARTICIPANTS: Patients aged ≥ 18 to 70 years with node positive or locally advanced nasopharyngeal carcinoma with ECOG performance score of 0 or 1 were enrolled.

STUDY DESIGN: An Observational prospective Study.

METHODS: This study was a hospital based prospective observational study conducted from Nov 2018 to Aug 2020. After taking informed consent, patients were administered two cycles of neoadjuvant chemotherapy (docetaxel and cisplatin 75mg/m² intravenous  each) three weekly apart followed by IMRT to a dose of 70 Gy/35 fractions concurrent with weekly cisplatin 40 mg/m² intravenously. Patients were assessed for various acute toxicities weekly as per CTCAE version 5.0. At the completion of study, response outcome was done as per RECIST version 1.1 and Survival analysis was done by using Kaplan Meier survival. All the analysis were done by using SPSS-v-23.0 and the association between variables was shown by chi square test.

RESULTS: A total of 23 patients were recruited. However, only 20 patients completed the prescribed treatment as planned. During the course of treatment, 7 (33.34%) patients had treatment interruption for ≤ 1 week while as 8 (38.09%) patients had treatment interruption for > 1 week due to certain toxicities. The most common toxicities observed among these were oral mucositis (93.33%), skin ulceration (46.66%), febrile neutropenia (20.0%) & xerostomia (13.33%). At the time of response assessment, 12 (60%) patients had complete response, 6 (30%) patients had partial response, 1 (5.0%) patient had progression of disease in the form of axillary and liver metastasis, while as 1 (5.0%) patient progressed with bone metastasis. On completion of this study (period of twenty two months), 4 (17.39%) patients had expired and 19 (82.60%) patients were still alive. In our patients the mean DFS of 16.500 ± 1.342 months with DFS rate of 86.95%; and the mean OS of 19.726 ± 1.222 months with OS rate of 82.60%.

CONCLUSION:  Induction chemotherapy followed by concurrent chemoradiotherapy is better tolerable, safe, effective and feasible treatment option for patients with more advanced nasopharyngeal carcinoma.

IMPLICATIONS: The addition of induction chemotherapy to CCRT can be considered as one of the treatment modality for LANPC. However randomized comparison to other induction chemotherapy regimen and other treatment modalities is warranted.