Improving Efficacy, Reducing Toxicity and Reaching Primary Care: Chinese Researchers Pioneer a New Treatment Model for Nasopharyngeal Cancer
Recently, a team led by Professors Ma Jun and Sun Ying from the Sun Yat-sen University Cancer Center (Zhongshan) collaborated with Central South University Xiangya Hospital, Huazhong University of Science and Technology Union Hospital, Guizhou Medical University Affiliated Cancer Hospital, Guangxi Medical University Affiliated Cancer Hospital, Air Force Medical University First Affiliated Hospital, Huazhong University of Science and Technology Tongji The hospital and other units jointly completed a large-scale prospective phase 3 clinical trial, establishing for the first time a new model of capecitabine metronomic maintenance therapy after radiotherapy and chemotherapy for nasopharyngeal carcinoma. This model significantly improves patient survival while having low side effects, is easy to use, and is cheap, which is conducive to promotion and treatment at the grassroots level.
On the afternoon of June 7, local time in the United States, Professor Ma Jun was invited to give an oral report on the research results at the American Annual Society of Clinical Oncology (ASCO), known as the "Oscars" of oncology. This study was also published in the top international medical journal "The Lancet" and is an oncology study independently completed by scholars from mainland China (see link at the end of the article).
The incidence rate of nasopharyngeal cancer in China ranks first in the world. According to statistics from the World Health Organization, nearly half of the world's nasopharyngeal cancers occur in China. Due to the hidden location of nasopharyngeal cancer, more than 70% of patients are already in the local and regional advanced stage when they seek treatment. The treatment effect is poor and require a comprehensive treatment strategy of radiotherapy combined with chemotherapy. Although more than 95% of patients can achieve complete clinical remission after radiotherapy and chemotherapy, due to latent systemic microscopic lesions, up to 30% of patients experience disease progression within 3 years after the end of treatment, and patients have poor physical tolerance after radiotherapy and chemotherapy, making it difficult to continue to tolerate high-intensity traditional chemotherapy. This has become a bottleneck restricting the further improvement of the efficacy of nasopharyngeal cancer, and is also a major problem that urgently needs to be solved in clinical practice.
Capecitabine metronomic maintenance therapy has significant efficacy and outstanding advantages. Capecitabine is a classic chemotherapy drug that has been used clinically for many years. Unlike traditional chemotherapy, which uses the maximum tolerated dose to treat tumors, capecitabine can be maintained at a relatively low blood concentration for a long time through low-dose, long-term oral administration, thereby reducing toxic and side effects while continuing to fight tumors. It is especially suitable for maintenance treatment of patients after radiotherapy and chemotherapy.
Inspired by this, Sun Yat-sen University Cancer Center took the lead in conducting this multi-center, randomized controlled study in 2016, recruiting a total of 406 patients with high-risk locoregional advanced nasopharyngeal carcinoma. The study was successfully completed this year and achieved encouraging results: the use of capecitabine metronomic maintenance therapy for one year after radical chemoradiotherapy increased the 3-year disease-free survival rate from 75.7% to 85.3%. At the same time, this model has good safety. Compared with the previous traditional chemotherapy, which had an incidence rate of severe toxic side effects of about 40% to 80%, the incidence rate of severe toxic side effects in this model is only 17%, which is tolerable to patients. It is worth mentioning that the total cost of capecitabine maintenance treatment for one year is less than 5,000 yuan, and it is an oral treatment. It is convenient to use and has a high degree of acceptance by patients. Its cost-effectiveness and popularity are self-evident.
Persistently optimize treatment strategies, from "toxicity reduction" to "efficiency enhancement" and then to "improving efficacy and reducing toxicity". Since 1998, international guidelines have recommended that patients with locally advanced nasopharyngeal carcinoma receive three courses of high-intensity traditional adjuvant chemotherapy after chemoradiotherapy. However, Professor Ma Jun's team observed that this regimen is highly toxic and difficult for patients to complete. Through multi-center, prospective clinical trials, they found that this regimen did not improve the efficacy, but instead increased the toxic side effects and economic burden of patient treatment. The research results were published in The Lancet Oncology in 2012. The article was adopted by international guidelines the year after it was published, changing the textbook regimen of traditional adjuvant chemotherapy that had been used internationally for 15 years. Regarding when to start chemotherapy, Professor Ma Jun’s team proposed that chemotherapy should be carried out before radiotherapy, that is, induction chemotherapy, because a large number of patients have micro-metastasis throughout the body before radiotherapy, and the patients are in good health before radiotherapy. In this regard, Professor Ma Jun's team confirmed the effectiveness of induction chemotherapy through a second study. The research results were published in "The Lancet·Oncology" in 2016. The international guidelines once again adopted the research results, and induction chemotherapy became the preferred chemotherapy opportunity. However, the above-mentioned induction chemotherapy uses a three-drug regimen of docetaxel + cisplatin + fluorouracil. Although it is effective, it is highly toxic and difficult to promote at the grassroots level. How to reduce the incidence of toxic and side effects while ensuring efficacy has become the focus of further research. In this regard, Professor Ma Jun's team proposed a new two-drug intravenous chemotherapy regimen of "gemcitabine + cisplatin". Clinical trials have confirmed that this regimen can significantly reduce the risk of distant metastasis in patients and has less side effects during treatment. The research results were published in the "New England Journal of Medicine" in 2019. International guidelines also regard "gemcitabine + cisplatin" as the preferred induction chemotherapy regimen. On this basis, this study will further solve the problem of disease progression in patients after radical chemoradiotherapy. In an editorial published in the same issue, Professor Robert Kerbel from the University of Toronto in Canada spoke highly of this study, believing that this new model of maintenance treatment can change clinical practice. It not only brings survival benefits to patients after high-intensity radiotherapy and chemotherapy, but also establishes an anti-cancer model that is convenient and accessible and can benefit the grassroots.
Team of Professors Ma Jun and Sun Ying
Passing on the fire for generations, looking back at the path of research on nasopharyngeal cancer at Sun Yat-sen University Cancer Center. When the institute was founded in 1964, Sun Yat-sen University Cancer Center targeted the "Guangdong tumor" - nasopharyngeal cancer, a malignant tumor that seriously endangers people's health in South China, as the target of research and victory. Generations of people have passed on the fire, fearing no hardships, and constantly exploring, advancing step by step in basic and clinical research, promoting continuous breakthroughs in the clinical diagnosis and treatment of nasopharyngeal cancer in the era of personalized and precise diagnosis and treatment, and benefiting the majority of patients.
Brief introduction of the main researcher Ma Jun (corresponding author) is a professor, executive deputy director and vice president of the Sun Yat-sen University Cancer Center. He serves as the convener of the Special Medicine Evaluation Group of the Academic Degrees Committee of the State Council and the first chairman of CSCO. Published many high-level papers as corresponding author, including N Eng J Med, Lancet*2, Lancet Oncol*4, J Clin Oncol, BMJ, Cell Res, etc. Won 2 key projects of the National Natural Science Foundation, led the team to be selected into the "Innovation Team of the Ministry of Education, Key Area Innovation Team of the Ministry of Science and Technology", and won 2 second prizes of the National Science and Technology Progress Award as the first completer (2009, 2015), the first National Innovation Certificate, the Guangdong Provincial Outstanding Contribution Award, etc. Sun Ying (co-corresponding author) is professor, deputy director and vice president of Sun Yat-sen University Cancer Center, winner of the National High-Level Talent Project. Committed to research on precision radiotherapy and optimization of comprehensive treatment strategies for nasopharyngeal cancer, he has published many high-level papers as the corresponding author (including co-authors), including N Eng J Med, Lancet*2, J Clin Oncol, Mol Cancer, J Pineal Res, Nat Commun*2, Clin Cancer Res, Cancer Res, Radiology, etc. He has won 1 national key research and development project, 1 National Natural Science Foundation Mathematics Tianyuan Fund, 2 second-class National Science and Technology Progress Awards, etc.
Xie Fangyun (co-corresponding author) is a professor and doctoral supervisor at the Sun Yat-sen University Cancer Center. He is committed to research on nasopharyngeal cancer staging optimization and comprehensive treatment strategy optimization. Published many high-level papers as corresponding author (including co-author), including Ann Oncol, Lancet Oncol, N Eng J Med, Lancet, etc.
Tang Linglong (co-corresponding author) is the chief physician and doctoral supervisor of the Sun Yat-sen University Cancer Center. She is committed to research on comprehensive chemoradiotherapy treatment strategies for nasopharyngeal cancer and individualized radiotherapy target areas. Published many high-level papers as corresponding author (including co-author), including BMC Med, Clin Cancer Res, Lancet Oncol, Lancet, etc.
Original link: https://doi.org/10.1016/S0140-6736
Text/Department of Radiotherapy