Wai-Tong Ng1, Stewart Y Tung2, Victor Lee3, Roger K C Ngan4, Horace C W Choi3, Lucy L K Chan1, To-Wai Leung5, Lillian L Siu6, Tai-Xiang Lu7, Terence Tan8, Eng-Huat Tan8, Henry C K Sze1, Alice W Y Ng2, Harry H Y Yiu4, Brian O'Sullivan6, Rick Chappell9, Anne W M Lee10. 1. Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. 2. Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China. 3. Departments of Clinical Oncology, The University of Hong Kong and the University of Hong Kong-Shenzhen Hospital, Hong Kong, China. 4. Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China. 5. Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, China. 6. Ontario Cancer Institute, Princess Margaret Cancer Centre, Toronto, Canada. 7. Cancer Center, Sun Yat Sen University, Guangzhou, China. 8. Department of Clinical Oncology, National Cancer Center, Singapore. 9. Department of Biostatistics, University of Wisconsin Medical School, Madison, Wisconsin. 10. Departments of Clinical Oncology, The University of Hong Kong and the University of Hong Kong-Shenzhen Hospital, Hong Kong, China. Electronic address: annelee@hku-szh.org.
Abstract
PURPOSE: This is an updated combined analysis of 2 randomized studies (NPC-9901 and NPC-9902 trials) to evaluate the 10-year outcome attributed to the addition of concurrent-adjuvant chemotherapy for advanced locoregional nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Eligible patients with stage III-IVBnonkeratinizing NPC were randomly assigned to radiation therapy alone (RT: 218 patients) or chemoradiation therapy (CRT: 223 patients) using 3 cycles of cisplatin (100 mg/m2) concurrent with RT, followed by 3 cycles of cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/day for 4 days). All of the patients were irradiated with conventional fractionation to ≥66 Gy. The median follow-up was 13.9 years. RESULTS: Intention-to-treat analysis confirmed that the CRT group achieved significant improvement in 10-year failure-free rate (FFR: 62% vs 52%, P = .016), progression-free survival rate (PFS: 56% vs 44%, P = .008), and overall survival rate (OS: 60% vs 50%, P = .044). There was no significant increase in overall late toxicity rate (51% vs 48%, P = .34) or noncancer deaths (19% vs 16%, P = .52). Exploratory studies showed no difference in disease control between 2 or 3 cycles of concurrent cisplatin; however, patients given 3 concurrent cycles had a significant increase in hearing impairment (40% vs 24%, P = .017). Only those who continued to receive 2 or more cycles of adjuvant cisplatin-fluorouracil achieved significant improvement in distant control (73% vs 65%, P = .037) and maximal survival gain. CONCLUSION: The addition of concurrent cisplatin plus adjuvant cisplatin-fluorouracil could significantly improve overall survival and disease control without incurring a significant increase in late toxicity or noncancer deaths. Exploratory analyses suggested that both the concurrent and the adjuvant phases contributed to tumor control. Furthermore, the number of concurrent cycles could be reduced from 3 to 2 cycles in order to achieve a similar survival benefit without incurring an excessive increase in hearing impairment. This is a useful hypothesis that warrants further validation.
RCT Entities:
PURPOSE: This is an updated combined analysis of 2 randomized studies (NPC-9901 and NPC-9902 trials) to evaluate the 10-year outcome attributed to the addition of concurrent-adjuvant chemotherapy for advanced locoregional nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Eligible patients with stage III-IVB nonkeratinizing NPC were randomly assigned to radiation therapy alone (RT: 218 patients) or chemoradiation therapy (CRT: 223 patients) using 3 cycles of cisplatin (100 mg/m2) concurrent with RT, followed by 3 cycles of cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/day for 4 days). All of the patients were irradiated with conventional fractionation to ≥66 Gy. The median follow-up was 13.9 years. RESULTS: Intention-to-treat analysis confirmed that the CRT group achieved significant improvement in 10-year failure-free rate (FFR: 62% vs 52%, P = .016), progression-free survival rate (PFS: 56% vs 44%, P = .008), and overall survival rate (OS: 60% vs 50%, P = .044). There was no significant increase in overall late toxicity rate (51% vs 48%, P = .34) or noncancer deaths (19% vs 16%, P = .52). Exploratory studies showed no difference in disease control between 2 or 3 cycles of concurrent cisplatin; however, patients given 3 concurrent cycles had a significant increase in hearing impairment (40% vs 24%, P = .017). Only those who continued to receive 2 or more cycles of adjuvant cisplatin-fluorouracil achieved significant improvement in distant control (73% vs 65%, P = .037) and maximal survival gain. CONCLUSION: The addition of concurrent cisplatin plus adjuvant cisplatin-fluorouracil could significantly improve overall survival and disease control without incurring a significant increase in late toxicity or noncancer deaths. Exploratory analyses suggested that both the concurrent and the adjuvant phases contributed to tumor control. Furthermore, the number of concurrent cycles could be reduced from 3 to 2 cycles in order to achieve a similar survival benefit without incurring an excessive increase in hearing impairment. This is a useful hypothesis that warrants further validation.
Authors: Quynh Thu Le; A Dimitrios Colevas; Brian O'Sullivan; Anne W M Lee; Nancy Lee; Brigette Ma; Lillian L Siu; John Waldron; Chwee-Ming Lim; Nadeem Riaz; Jean Lynn; Shakun Malik Journal: J Natl Cancer Inst Date: 2019-07-01 Impact factor: 13.506
Authors: Zhong-Guo Liang; Fan Zhang; Bin-Bin Yu; Ling Li; Song Qu; Ye Li; Ying Guan; Ren-Ba Liang; Lu Han; Xiao-Dong Zhu Journal: Cancer Manag Res Date: 2020-02-04 Impact factor: 3.989