Randomized phase-III-trial of concurrent chemoradiation for locally advanced head and neck cancer comparing dose reduced radiotherapy with paclitaxel/cisplatin to standard radiotherapy with fluorouracil/cisplatin: The PacCis-trial

Background and purpose This multicenter, phase 3 trial investigates whether the incorporation of concurrent paclitaxel and cisplatin together with a reduced total dose of radiotherapy is superior to standard fluorouracil–cisplatin based CRT. Materials and methods Patients with SCCHN, stage III–IVB, were randomized to receive paclitaxel/cisplatin (PacCis)–CRT (arm A; paclitaxel 20 mg/m2 on days 2, 5, 8, 11 and 25, 30, 33, 36; cisplatin 20 mg/m2, days 1–4 and 29–32; RT to a total dose of 63.6 Gy) or fluorouracil/cisplatin (CisFU)–CRT (arm B; fluorouracil 600 mg/m2; cisplatin 20 mg/m2, days 1–5 and 29–33; RT: 70.6 Gy). Endpoint was 3-year-disease free survival (3y-DFS). Results A total of 221 patients were enrolled between 2010 and 2015. With a median follow-up of 3.7 years, 3y-DFS in the CisFU arm and PacCis arm was 58.2% and 48.4%, respectively (HR 0.82, 95% CI 0.56–1.21, p = 0.52). The 3y-OS amounted to 64.6% in the CisFU arm, and to 59.2% in the PacCis arm (HR 0.82, 95% CI 0.54–1.24, p = 0.43). In the subgroup of p16-positive oropharyngeal carcinomas, 3y-DFS and 3y-OS was 84.6% vs 83.9% (p = 0.653), and 92.3% vs. 83.5% (p = 0.76) in arm A and B, respectively. Grade 3–4 hematological toxicities were significantly reduced in arm A (anemia, p = 0.01; leukocytopenia, p = 0.003), whereas grade 3 infections were reduced in arm B (p = 0.01). Conclusion Paclitaxel/cisplatin–CRT with a reduced RT-dose is not superior to standard fluorouracil/cisplatin–CRT. Subgroup analyses indicate that a reduced radiation dose seems to be sufficient for p16+ oropharyngeal cancer or non-smokers. Clinical trial information: NCT01126216; EudraCT Number 2005-003484-23.