Raltitrexed versus 5-fluorouracil with cisplatin and concurrent radiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (LA-HNSCC): A randomized controlled multi-centered trial

Abstract

Background: CCRT has been considered to be the standard of treatment for LAHNSCC. However, patients receiving CCRT experience a substantial number of treatment‐ related adverse events, primarily causing oropharyngeal mucositis(OM) and leading to interruption or discontinuation of treatment. Raltitrexed is a specific thymidylate synthase inhibitor with a convenient administration, acceptable toxicity and radiosensitizing property, as the published phase I/II trials have shown. This study aimed to compare the clinical efficacy and toxicity of cisplatin with raltitrexed (RP) or 5‐fluorouracil (FP) for LA‐HNSCC. Methods: Eligible patients with LA‐HNSCC were randomly assigned in a 1:1 ratio to receive CCRT with either RP or FP. The RP group consisted of 2.5mg/m2 intravenous raltitrexed on day 1 and 25mg/m2 intravenous cisplatin on days 1‐3. The FP group consisted of continuous intravenous infusions of 600mg/m2 5‐fluorouracil on days 1‐5 and 25 mg/m2 intravenous cisplatin on days 1‐3. Chemotherapy was administrated concurrently with radiotherapy and was repeated every 3 weeks with completion of at least 2 cycles. Primary endpoint was PFS. Secondary endpoints were complete response rates(CRR), OS and safety. Results: A total of 108 patients with LA‐HNSCCenrolled in this study, with 52 patients assigned to the RP group and 56 patients to the FP group. There was no significant difference in CRR between the two arms (42.9%vs 26.8%, respectively, p=0.074), with the RP group showing a trend of increased CRR. Data of locoregional control, patterns of failure, and survival required further follow‐up. Themost frequent acute toxicities were bone marrow suppression, gastrointestinal side effects and O Min both arms. The incidence rate of severeOM was significantly lower (P<0.05) in the RP group than in the FP group. The incidence of other adverse effects seen in the two arms were similar (P>0.05). Conclusions: The efficacy of the RP regimen was similar to that of the FP regimen. The RP regimen had a tolerable safety profile, with a lower incidence of severeOMand, consequently, an improved quality of life. In conclusion, RP is an effective, well‐tolerated regimen for LA‐HNSCC.