Adding Induction Chemotherapy to Preoperative Concurrent Chemoradiotherapy Does Not Improve the Treatment Results in Locally Advanced Hypopharyngeal Carcinoma: A Randomized Phase II Trial

Abstract

The role of TPF induction chemotherapy followed by concurrent chemoradiotherapy in the locally advanced hypopharyngeal carcinoma is unclear. Based on the established treatment modality-preoperative concurrent chemoradiotherapy by our institution, we conduct a phase II study to determine the role of induction chemotherapy in locally advanced hypopharyngeal carcinoma. A total of 142 patients with stage III/IVA-B hypopharyngeal carcinoma were randomly assigned (in a 1:1 ratio) to induction chemotherapy followed by preoperative concurrent chemoradiotherapy group (IC+CCRT group) or preoperative radiotherapy alone group (CCRT group), 113 patients were analyzed. The induction chemoradiotherapy regimen consists of Paclitaxel 175 mg/m2, d1, d22; DDP 75 mg/m2, d1, 22 and 5-FU 750 mg/m2, d1-4, 22-25. Concurrent chemotherapy regimen was cisplatin 80mg/m2/d1,22,43. All patients who received preoperative concurrent chemoradiotherapy will be evaluated at DT 53Gy, only primary lesions reaching large PR are recommended for radical concurrent chemoradiotherapy, otherwise planned surgery. We use the Kaplan-Meier method and the log-rank test to analyze. With a medial follow-up of 40.4 month, the 3-year overall survival(OS), progression-free survival(PFS), locoregional control rates(LRC), distant metastasis-free survival(DMFS)and laryngectomy-free survival of the IC+CCRT group (n = 53) and the CCRT group(n = 60) were 55.7% vs 55.1%(P = 0.802), 44.7% vs 56.1%(P = 0.324), 58.4%vs 69.8%(P = 0.198), 75.4%vs77.7%(P = 0.983) and 86.3%vs 85.4%(P = 0.938).Subgroup analysis showed that, the 3-year OS, PFS, LRC, DMFS and laryngectomy-free survival for patients who only received IC+CCRT group (n = 46, who received two cycles of TPF and radical concurrent chemoradiotherapy) and the CCRT group(n = 45, who received the radical concurrent chemoradiotherapy), were 61.1% vs 49.4%(P = 0.314), 50.3% vs 51.3%(P = 0.926), 62.5% vs 68.4%(P = 0.526), 76.3% vs 75.2%(P = 0.717)and 96.0% vs 89.1%(P = 0.236). The 3-year OS, PFS, LRC, DMFS and laryngectomy-free survival were 63.6% vs 50.8%(P = 0.217), 52.8% vs 52.6%(P = 0.813), 63.9% vs 66.6%(P = 0.621), 73.8% vs 76.3%(P = 0.926) and 94.0% vs 84.7%(P = 0.151) in the patients who response to induction chemotherapy (n = 45, who reached PR after two cycles of TPF) and control group(n = 59). The most common failure patterns were locoregional recurrence, followed by distant metastasis, with rate of 26.5% and 18.6%. There was no difference between the two groups. The grade 3+ hematologic toxicities between IC+CCRT vs CCRT were 40.78% vs 5.08% (P<0.001). The major failure pattern of locally advanced hypopharyngeal carcinoma is local regional relapse. Adding induction of chemotherapy to preoperative concurrent chemoradiotherapy could not improve the survival and laryngectomy-free survival of local advanced hypopharyngeal cancer in the cost of higher acute hematology toxicities. Clinical trial information: NCT03558035.