Retrospective analysis of chronomodulated chemotherapy versus conventional chemotherapy with paclitaxel, carboplatin, and 5-fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

Dan Chen, Jue Cheng, Kai Yang, Yue Ma, Fang Yang

Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China

Background: Chronomodulated chemotherapy has emerged as a new therapy as a result of recent studies focusing on the biological clock. It has been demonstrated that combination chronomodulated chemotherapy of platinum-based drugs and 5-fluorouracil (5-Fu) can significantly improve efficacy and reduce the incidence of adverse events in patients with metastatic colorectal cancer, as compared with conventional chemotherapy. However, the results may be different in different tumors. Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is very difficult to treat, with an extremely unfavorable prognosis. So far, no report is available on chronomodulated chemotherapy for HNSCC.
Methods: Retrospective analyses were made on 49 patients with local recurrent and/or metastatic HNSCC who underwent palliative treatments with paclitaxel, carboplatin, and 5-Fu. The patients were divided into a chronomodulated chemotherapy group (28 patients) and a conventional chemotherapy group (21 patients) according to their administration times. The two groups were compared for tumor objective response rate, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events.
Results: The tumor objective response rate and patients' OS were significantly higher and longer in the chronomodulated chemotherapy group than in the conventional chemotherapy group (71.43% versus 42.86%, respectively, P<0.05; and median OS 15.3 months versus 10.6 months, respectively, P<0.05). However, PFS was similar statistically (median PFS 11.6 months versus 7.2 months, P>0.05). The global incidence of adverse events in the chronomodulated chemotherapy group was significantly lower than that in the conventional chemotherapy group (46.43% versus 76.19%, P<0.05), with significantly lower incidence of grade 3–4 adverse events (7.14% versus 33.33%, P<0.05).
Conclusion: Chronomodulated chemotherapy with paclitaxel, carboplatin, and 5-Fu may be a new and effective therapy for patients with recurrent and/or metastatic HNSCC as compared with conventional chemotherapy.

Keywords: chronotherapy, chronomodulated chemotherapy, head and neck cancer, palliative chemotherapy, paclitaxel, 5-fluorouracil, carboplatin