Nedaplatin: a new paradigm in nasopharyngeal cancer
Editorial

Nedaplatin: a new paradigm in nasopharyngeal cancer

Imjai Chitapanarux1, Chaiyut Charoentum2, Patrinee Traisathit3,4

1Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, 2Division of Oncology, Department of Medicine, Faculty of Medicine, 3Department of Statistic, Faculty of Science, 4Center of Excellence in Bioresources for Agriculture, Industry and Medicine, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand

Correspondence to: Imjai Chitapanarux. Division of Radiation Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Email: imjai@hotmail.com or imjai.chitapanarux@cmu.ac.th.

Comment on: Tang LQ, Chen DP, Guo L, et al. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 2018;19:461-73.


Received: 17 May 2018; Accepted: 22 June 2018; Published: 30 June 2018.

doi: 10.21037/anpc.2018.06.01


Radiotherapy concurrent with cisplatin either weekly or every 3 weeks’ regimen has been accepted as the standard of care for locoregional advanced stage of nasopharyngeal cancer for decades (1-5). Although it has shown a statistically significant benefit in terms of locoregional control and survival rate when compared with radiotherapy alone, but severe acute and late toxicities might affect the quality of life (QoL), mainly nausea, vomiting, impaired renal function, and hearing toxicity (6-9).

Acute toxicities mainly in hematologic and renal toxicity of chemotherapy also had the effect on the compliance of treatment. The intergroup 0099 study reported the compliance of concurrent chemoradiotherapy (CCRT) in only 63% (1). The Thai study using the same regimen of CCRT as in the intergroup 0099 also demonstrated the similar result of compliance rate of CCRT at 59% (10).

Several new chemotherapy regimens in combination with radiotherapy were studied to find the best way to improve both in efficacy and toxicities. For example, a more convenient carboplatin—based chemoradiotherapy had been tested and showed better tolerability with a lower rate of severe gastrointestinal toxicities and nephrotoxicities than of standard cisplatin-based regimen (10). However, the efficacy of carboplatin-based chemoradiotherapy had not been consistently confirmed to improve outcome by others investigators.

Nedaplatin is a recent promising alternative drug for cisplatin which had shown a good potential for radiosensitizer activity in early studies with less nephrotoxicity and gastrointestinal toxicity compared to the incidence reported from cisplatin-based regimen (11-13). Tang et al. have successfully performed an open labeled randomized trial comparing nedaplatin to cisplatin both given at 100 mg/m2 every 3 weeks concurrent with intensity-modulated radiotherapy in stage II–IVB, nasopharyngeal carcinoma in 2 hospitals in China. The investigators reported the 2-year progression-free survival as primary end point in the nedaplatin group is non-inferior to cisplatin group, with the difference of 1.9% and 1.0% in the intention-to-treat and per protocol population analysis respectively. Nedaplatin also had an advantage of more convenient administration without the requirement for intravenous fluid hydration and diuretics for renal protection. Analysis of safety showed that nedaplatin group had significant less acute grade 3 or 4 toxicity of nausea (2% vs. 9%), vomiting (6% vs. 18%) and anorexia (13% vs. 27%) than cisplatin group. Patient in nedaplatin group had higher frequency of severe grade 3 or 4 thrombocytopenia than in cisplatin group (6% vs. 2%). The late toxicity of grade 3 or 4 auditory or hearing was less frequent in nedaplatin group than cisplatin group (2% vs. 6%). The investigators however found that treatment compliance of patient in nedaplatin group who could receive 3 cycles of concurrent treatment was lower than in cisplatin group (57% vs. 65%) and could be a confounder when determining the difference in treatment associated toxicity between two groups. About 17% of patients in nedaplatin group had thrombocytopenia and require treatment delay exceeded the timeframe of third cycle of nedaplatin administration. In post-hoc analysis in subset of patients who could receive all 3 cycles of nedaplatin or cisplatin, the investigators reported no different in either occurrence of locoregional relapse, distant relapse or survival between two groups.

An update of the MAC-NPC meta-analysis (12) demonstrated a survival benefit at 5 years by 6.3% and had a benefit in all endpoints (progression-free survival, locoregional control, distant control, and cancer mortality) in locoregionally advanced disease treated by CCRT with or without adjuvant chemotherapy. The scheme of treatment in this study using CCRT with nedaplatin without adjuvant chemotherapy which is the common practice for the treatment of nasopharyngeal cancer in many Asian countries. This study prescribed the dose to the skull base, clivus, sphenoid sinus, parapharyngeal space, pterygoid fossae, posterior parts of the nasal cavity, pterygopalatine fossae, retropharyngeal nodal regions, and lymph node level IB to level V lower (54–56 Gy) than other guidelines (56–60 Gy). Nevertheless, the locoregional relapse rate at 2 years was acceptable and similar to the historical data. This study appropriately controlled the quality of radiotherapy treatment protocol which is the utmost imperative treatment component and an important factor of treatment achievement for NPC patients.

Focus to the financial difficulties domain in EORTC QLQ-C30 in this study, as we know that socioeconomic status was the most substantial flexible that correlated with the QoL. Lam et al. (13) studied the household income of Chinese adults and demonstrated that low-income households had poorer QoL and also was the threshold for weakening of both physical and mental QoL. Besides, the distribution of socioeconomic status of the patients in both groups was not described in this study.

This study is clearly stated primary and secondary endpoints. This is a properly reported statistical methodology, logical and rational concept of the study and the use of appropriate study design (randomized controlled trial). Non-inferiority trial enables a direct comparison of the effectiveness of new concurrent chemotherapy regimen; nedaplatin and a standard-of-care regimen. The study provides an accurate description of target population, explanation of the sample size calculation, randomization, allocation and blocking in enough details relevant data for multicenter clinical trial. They did valid description and sufficient explanation of statistical tests. However, they did not plan to undertake any interim analyses. It is also shows the high proportion of eligible patients who were randomized, the small number not getting their randomized treatment (but still included in intention to treat analysis), and the small numbers removed from analysis or lost to follow-up.

This was a randomized phase 3 trial with a large number of patients with good quality control of radiotherapy. The results of this study appeared promising. However, it is crucial to wait for the long term outcome of efficacy of overall survival and toxicity of these regimens and data of cost-effective analysis before we could firmly conclude that nedaplatin based concurrent chemotherapy could be an alternative treatment option to the long standing standard cisplatin-based regimen during radiotherapy in patients with nasopharyngeal cancer.


Acknowledgements

None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


References

  1. Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. J Clin Oncol 1998;16:1310-7. [Crossref] [PubMed]
  2. Chan AT, Teo PM, Ngan RK, et al. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol 2002;20:2038-44. [Crossref] [PubMed]
  3. Wee J, Tan EH, Tai BC, et al. Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety. J Clin Oncol 2005;23:6730-8. [Crossref] [PubMed]
  4. Chan AT, Leung SF, Ngan RK, et al. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 2005;97:536-9. [Crossref] [PubMed]
  5. Chen Y, Liu MZ, Lian SB, et al. Preliminary results of a prospective randomized trial comparing concurrent chemoradiotherapy plus adjuvant chemotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma in endemic regions of China. Int J Radiat Oncol Biol Phys 2008;71:1356-64. [Crossref] [PubMed]
  6. Kim TH, Ko YH, Lee MA, et al. Treatment Outcome of Cisplatin-based Concurrent Chemoradiotherapy in the Patients with Locally Advanced Nasopharyngeal Cancer. Cancer Res Treat 2008;40:62-70. [Crossref] [PubMed]
  7. Kwong DL, Wei WI, Sham JS, et al. Sensorineural hearing loss in patients treated for nasopharyngeal carcinoma: a prospective study of the effect of radiation and cisplatin treatment. Int J Radiat Oncol Biol Phys 1996;36:281-9. [Crossref] [PubMed]
  8. Chan SH, Ng WT, Kam KL, et al. Sensorineural hearing loss after treatment of nasopharyngeal carcinoma: a longitudinal analysis. Int J Radiat Oncol Biol Phys 2009;73:1335-42. [Crossref] [PubMed]
  9. Wei Y, Zhou T, Zhu J, et al. Long-term outcome of sensorineural hearing loss in nasopharyngeal carcinoma patients: comparison between treatment with radiotherapy alone and chemoradiotherapy. Cell Biochem Biophys 2014;69:433-7. [Crossref] [PubMed]
  10. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomized, non-inferiority, open trial. Eur J Cancer 2007;43:1399-406. [Crossref] [PubMed]
  11. Tang LQ, Chen DP, Guo L, et al. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 2018;19:461-73. [Crossref] [PubMed]
  12. Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis. Lancet Oncol 2015;16:645-55. [Crossref] [PubMed]
  13. Lam CLK, Guo VY, Wong CKH, et al. Poverty and health-related quality of life of people living in Hong Kong: comparison of individuals from low-income families and the general population. J Public Health (Oxf) 2017;39:258-65. [PubMed]
doi: 10.21037/anpc.2018.06.01
Cite this article as: Chitapanarux I, Charoentum C, Traisathit P. Nedaplatin: a new paradigm in nasopharyngeal cancer. Ann Nasopharynx Cancer 2018;2:10.