A prospective phase II open-label randomized controlled trial to compare mandibular preservation in upfront surgery to neoadjuvant chemotherapy followed by surgery in operable oral cavity cancer.

Abstract

6518 Background: The study objective was to evaluate the non-Inferiority of survival and ability to preserve mandible with the use of neoadjuvant chemotherapy (NACT) in locally advanced oral cancers compared to upfront surgery alone without compromising survival. Methods: This study was a randomized, single centre, non-inferiority trial. Eligibility criteria included treatment naïve histologically confirmed cancer of the oral cavity; cancers requiring segmental resection for paramandibular disease without clinicoradiological evidence of bone erosion, clinical T2, T3 and T4, any N, M0 as per TNM (AJCC) 7th edition, age at least 18 years; and written informed consent. The patients were randomly assigned (1:1) to receive either upfront surgery followed by adjuvant treatment (Standard arm-SA) or receive two cycles of three drugs NACT (Docetaxel, Cisplatin, 5-Flurouracil) at three weekly interval (Intervention arm-IA). Depending on the response after two cycles, the patient would either receive an additional third cycle or undergo surgery followed by adjuvant treatment as decided by the tumour board. The primary endpoint was mandible preservation rate at 30% in the experimental arm. The secondary end points being Loco regional control and treatment related toxicity. Results: Between September 2010 and April 2013, 68 patients were enrolled and randomized to SA (34 patients) and IA (34 patients) with a median follow-up of 3.6 years (IQR 0.95- 7.05 years). Majority of the patients were T4 (n = 40, 58.8%) In the IA 28 patients had partial response (n = 28,82.4%), with a mandible preservation (Marginal Mandibulectomy) rate of 48% (n = 16/34). There were no close or positive margins in the IA. All patients received adjuvant treatment. The number of recurrences was similar in both the arms. All patients in the IA developed toxicities with the majority developing Grade III-IV toxicities (Grade III: 14, 41.2%, Grade IV: 11, 32.4%) (p = 0.739). The disease free survival (DFS) (p = 0.715, HR 0.911[0.516-1.607]) and overall survival (OS) (p = 0.747, HR 0.899[0.510-1.587]) were similar in both the arms. Conclusions: NACT seems to be a feasible option for mandibular preservation with acceptable toxicities in a select group of patients without compromising survival. However this needs to be tested in a larger phase III randomized trial. Clinical trial information: CTRI/2015/11/006396 .