Remarkable response to cetuximab-containing chemotherapy for tongue cancer refractory to immune checkpoint inhibitors

Abstract

Background: To establish a new chemotherapy platform for esophageal cancer, we conducted studies using a combination chemotherapy composed of docetaxel, nedaplatin, and 5-FU (DNF) for neoadjuvant chemotherapy (NAC) or definitive chemoradiation therapy (CRT). Method(s): Phase II study of NAC-DNF: Patients with stage IB to III received three cycles of docetaxel 30 mg/m2 and nedaplatin 50 mg/m2 on days 1 and 8, and a continuous infusion of 5-fluorouracil 400 mg/m2 on days 1 to 5 and 8 to 12, every three weeks followed by esophagectomy. The primary endpoint was the completion rate of NAC. Phase I/II study of CRT using DNF (DNF-R): Patients with stage IB to IV received two courses of DNF with concurrent radiotherapy (59.4 Gy/33 fractions). The primary endpoint was the complete response rate. Safety, progression-free survival (PFS) and overall survival (OS) were evaluated for the secondary endpoints. Result(s): NAC-DNF study: Nineteen patients were included. Eighteen (94.7%) patients completed three courses of DNF therapy. The most common grade 3 or 4 toxicity was neutropenia (26.3%). Eighteen (94.7%) achieved R0 resection, with five pathological complete response. No treatment-related deaths were observed. At the time of analysis, 17 patients survived without recurrence. DNF-R study: In the phase 1 study, the doselimiting toxicities were neutropenia and thrombocytopenia. The recommended dose of docetaxel was determined to be 20 mg/m2. In the phase 2 study, 28 patients were enrolled, with a median age of 64. Grade 3/4 acute toxicity included neutropenia (32.7%), febrile neutropenia (7.14%), thrombocytopenia (17.9%), and esophagitis (21.4%). Grade 3/4 late radiotoxicity included esophagostenosis (10.7%). All patients showed a response, including 23 (82.1%) complete responses. PFS and OS were both 41.2 months. Conclusion(s): DNF showed good tolerability and strong antitumor activity, suggesting that it is a potentially effective therapeutic regimen for esophageal cancer.