Abstract

// Ting Jin 1,2,* , Wei-feng Qin 1,2,* , Feng Jiang 1,2 , Qi-feng Jin 1,2 , Qi-chun Wei 3 , Xiu-wen Tang 4 , Yong-shi Jia 5 , Xiao-nan Sun 6 , Wen-feng Li 7 , Xing-lai Feng 1,2 and Xiao-zhong Chen 1,2 1 Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China 2 Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China 3 Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The SecondAffiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China 4 Department of Biochemistry and Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China 5 Department of Radiation Oncology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China 6 Department of Radiation Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China 7 Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China * These authors have contributed equally to this study Correspondence to: Xiao-zhong Chen, email: // Keywords : nasopharyngeal carcinoma, chemotherapy, concurrent chemoradiation, radiotherapy, docetaxel Received : May 18, 2016 Accepted : June 15, 2016 Published : July 28, 2016 Abstract In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 276 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS benefit was observed for TPF compared to PF, though this difference was not statistically significant (84.5% vs. 77.9%, P = 0.380). Due to increased frequencies of grade 3 or 4 neutropenia and diarrhea, significantly more patients in the TPF group required treatment delays and dose modifications. Our findings suggest that PF induction chemotherapy has substantially better tolerance and compliance rates than TPF induction chemotherapy. However, the treatment efficacy of PF is not superior to TPF induction chemotherapy in patients with locoregionally-advanced NPC (ClinicalTrials.gov number, NCT01536223).

Highlights

  • Treatment outcomes for locoregionally-advanced nasopharyngeal cancer (NPC) remain unsatisfactory, with 5-year overall survival (OS) rates of 53-80% and 28-61% for stage III and IV NPC, respectively [1,2,3,4,5,6,7,8].Numerous studies have explored neoadjuvant, concurrent and adjuvant chemotherapy

  • In the TPF group, docetaxel was decreased to 60 mg/m2 in the second course for 60 patients because of grade 4 neutropenia and/or thrombocytopenia, cisplatin decreased to 60 mg/m2 in the third course for 7 patients due to grade 4 neutropenia and/or thrombocytopenia after docetaxel, and fluorouracil decreased by 120 mg/m2 for 11 patients due to grade 3 mucositis or diarrhea

  • In the PF group, cisplatin was decreased to 80 mg/m2 for 21 patients because of grade 4 neutropenia and/or thrombocytopenia and fluorouracil decreased by 160 mg/m2 for 8 patients because of grade 3 mucositis or diarrhea

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Summary

Introduction

Treatment outcomes for locoregionally-advanced nasopharyngeal cancer (NPC) remain unsatisfactory, with 5-year overall survival (OS) rates of 53-80% and 28-61% for stage III and IV NPC, respectively [1,2,3,4,5,6,7,8].Numerous studies have explored neoadjuvant, concurrent and adjuvant chemotherapy. NACT based on docetaxel with cisplatin and 5-fluorouracil (TPF) provided a significant survival benefit in locally-advanced squamous cell carcinoma of the head and neck (SCCHN) compared to cisplatin-fluorouracil (PF) before either definitive radiotherapy (TAX323 trial) or carboplatin-based CCRT (TAX324 trial) [19,20]. In contrast to other head and neck squamous cell carcinomas, NPC is more chemosensitive and radiosensitive and has a proven association with EpsteinBarr virus. It remains unknown whether TPF induction chemotherapy significantly prolongs survival compared to PF induction chemotherapy in patients with locoregionally-advanced NPC receiving CCRT. We undertook a multi-center, open-label, randomized, noninferiority trial to compare PFS, tolerance and compliance to TPF + CCRT versus PF + CCRT in Chinese patients with locoregionally-advanced NPC

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