Skip to main content

Advertisement

SpringerLink
Log in

IMRT combined with S-1 concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective phase II study

  • PHASE II STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Purpose The current standard treatment for locally advanced nasopharyngeal carcinoma (LANPC) is intensity-modulated radiation therapy (IMRT) plus cisplatin concurrent chemoradiotherapy (CCRT). However, this regimen has well-known hematological and gastrointestinal toxicities. Many studies have reported that S-1 was effective in the treatment of multiple solid cancers with mild toxicities. However, knowledge regarding IMRT plus S-1 CCRT in LANPC is lacking. Therefore, we conducted this prospective phase II trial to evaluate the efficacy and safety of this regimen in LANPC. Patients and Methods Eligible patients with histologically confirmed LANPC were enrolled in this study. IMRT was given in 30–32 fractions five times per week. Concurrently, S-1 was administrated twice per day orally based on the body surface area (BSA < 1.25 m2, 30 mg; BSA: 1.25–1.5 m2, 40 mg; BSA > 1.5 m2, 50 mg). The primary endpoints were progression-free survival (PFS) and adverse events. Results From August 1, 2013, to December 15, 2017, 131 patients were enrolled in this study. The distribution of disease stages among the patients was as follows: 21 patients were in stage II (16.0%), 42 patients were in stage III (32.0%), and 68 patients were in stage IV (52.0%). After CCRT, the 3-year PFS, overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates were 87.4%, 95.7%, 94.7%, and 91.5%, respectively. The severity of most toxicities was mild. Approximately two-thirds of patients had no hematological toxicity. Grade 2 hematological toxicities included leukopenia (11.5%), anemia (1.5%), and thrombocytopenia (0.8%). Grade 3 hematological toxicities were rarely observed. Conclusion The results demonstrated that IMRT plus S-1 CCRT was effective with mild toxicity for patients with LANPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Chua MLK, Wee JTS, Hui EP, Chan ATC (2016) Nasopharyngeal carcinoma. Lancet 387(10022):1012–1024. https://doi.org/10.1016/s0140-6736(15)00055-0

    Article  PubMed  Google Scholar 

  2. Razak AR, Siu LL, Liu FF, Ito E, O'Sullivan B, Chan K (2010) Nasopharyngeal carcinoma: the next challenges. Eur J Cancer 46(11):1967–1978. https://doi.org/10.1016/j.ejca.2010.04.004

    Article  PubMed  Google Scholar 

  3. Chia WK, Teo M, Wang WW, Lee B, Ang SF, Tai WM, Chee CL, Ng J, Kan R, Lim WT, Tan SH, Ong WS, Cheung YB, Tan EH, Connolly JE, Gottschalk S, Toh HC (2014) Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent nasopharyngeal carcinoma. Mol Ther 22(1):132–139. https://doi.org/10.1038/mt.2013.242

    Article  CAS  PubMed  Google Scholar 

  4. Globacon (2012) http://gco.iarc.fr/

  5. You R, Sun R, Hua YJ, Li CF, Li JB, Zou X, Yang Q, Liu YP, Zhang YN, Yu T, Cao JY, Zhang MX, Jiang R, Mo HY, Guo L, Cao KJ, Lin AH, Qian CN, Sun Y, Ma J, Chen MY (2017) Cetuximab or nimotuzumab plus intensity-modulated radiotherapy versus cisplatin plus intensity-modulated radiotherapy for stage II-IVb nasopharyngeal carcinoma. Int J Cancer 141(6):1265–1276. https://doi.org/10.1002/ijc.30819

    Article  CAS  PubMed  Google Scholar 

  6. Tang L-Q, Chen D-P, Guo L, Mo H-Y, Huang Y, Guo S-S, Qi B, Tang Q-N, Wang P, Li X-Y, Li J-B, Liu Q, Gao Y-H, Xie F-Y, Liu L-T, Li Y, Liu S-L, Xie H-J, Liang Y-J, Sun X-S, Yan J-J, Wu Y-S, Luo D-H, Huang P-Y, Xiang Y-Q, Sun R, Chen M-Y, Lv X, Wang L, Xia W-X, Zhao C, Cao K-J, Qian C-N, Guo X, Hong M-H, Nie Z-Q, Chen Q-Y, Mai H-Q (2018) Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. https://doi.org/10.1016/s1470-2045(18)30104-9

  7. Guigay J, Temam S, Bourhis J, Pignon JP, Armand JP (2006) Nasopharyngeal carcinoma and therapeutic management: the place of chemotherapy. Ann Oncol 17(Suppl 10):x304–x307. https://doi.org/10.1093/annonc/mdl278

    Article  PubMed  Google Scholar 

  8. Chan BATC, Teo PML, Ngan RK, Leung TW (2002) 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 20(8):2038–2044

    Article  CAS  PubMed  Google Scholar 

  9. Lee AWM, Tung SY, Ng WT, Lee V, Ngan RKC, Choi HCW, Chan LLK, Siu LL, Ng AWY, Leung TW, Yiu HHY, O'Sullivan B, Chappell R (2017) A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10-year outcomes for efficacy and toxicity. Cancer 123(21):4147–4157. https://doi.org/10.1002/cncr.30850

    Article  CAS  PubMed  Google Scholar 

  10. Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R, Tung R, Siu L, Ng WT, Sze WK, Au GK, Law SC, O'Sullivan B, Yau TK, Leung TW, Au JS, Sze WM, Choi CW, Fung KK, Lau JT, Lau WH (2010) Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst 102(15):1188–1198. https://doi.org/10.1093/jnci/djq258

    Article  PubMed  Google Scholar 

  11. Wen L, You C, Lu X, Zhang L (2015) Phase II trial of concurrent chemoradiotherapy with S-1 versus weekly cisplatin for locoregionally advanced nasopharyngeal carcinoma. Mol Clin Oncol 3(3):687–691. https://doi.org/10.3892/mco.2015.529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lee AW, Lau WH, Tung SY, Chua DT, Chappell R, Xu L, Siu L, Sze WM, Leung TW, Sham JS, Ngan RK, Law SC, Yau TK, Au JS, O'Sullivan B, Pang ES, O SK, Au GK, Lau JT, Hong Kong Nasopharyngeal Cancer Study G (2005) Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 trial by the Hong Kong nasopharyngeal Cancer study group. J Clin Oncol 23(28):6966–6975. https://doi.org/10.1200/JCO.2004.00.7542

    Article  CAS  PubMed  Google Scholar 

  13. Franck C, Canbay A, Malfertheiner P, Venerito M (2017) Neoadjuvant treatment with cisplatin and S-1 in elderly patients with oesophagogastric adenocarcinoma and locoregional disease: two case reports and review of the literature. Mol Clin Oncol 7(6):1069–1072. https://doi.org/10.3892/mco.2017.1445

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lee DW, Lee KH, Kim HJ, Kim TY, Kim JS, Han SW, Oh DY, Kim JH, Im SA, Kim TY (2018) A phase II trial of S-1 and oxaliplatin in patients with advanced hepatocellular carcinoma. BMC Cancer 18(1):252. https://doi.org/10.1186/s12885-018-4039-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Peng PJ, Cheng H, Ou XQ, Zeng LJ, Wu X, Liu YM, Lin Z, Tang YN, Wang SY, Zhang HY, Chen ZB (2014) Safety and efficacy of S-1 chemotherapy in recurrent and metastatic nasopharyngeal carcinoma patients after failure of platinum-based chemotherapy: multi-institutional retrospective analysis. Drug Des Devel Ther 8:1083–1087. https://doi.org/10.2147/DDDT.S67592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takagi M, Sakata K, Someya M, Tauchi H, Iijima K, Matsumoto Y, Torigoe T, Takahashi A, Hareyama M, Fukushima M (2010) Gimeracil sensitizes cells to radiation via inhibition of homologous recombination. Radiother Oncol 96(2):259–266. https://doi.org/10.1016/j.radonc.2010.05.020

    Article  CAS  PubMed  Google Scholar 

  17. Suzuki S, Honda K, Sato T, Yamazaki K, Ishikawa K (2015) Feasibility and toxicity of adjuvant chemotherapy using S-1 granules for local advanced squamous cell carcinoma of the head and neck. J Chemother 27(5):297–300. https://doi.org/10.1179/1973947815Y.0000000014

    Article  CAS  PubMed  Google Scholar 

  18. Kitani Y, Kubota A, Furukawa M, Hori Y, Nakayama Y, Nonaka T, Mizoguchi N, Kitani Y, Hatakeyama H, Oridate N (2017) Impact of combined modality treatment with radiotherapy and S-1 on T2N0 laryngeal cancer: possible improvement in survival through the prevention of second primary cancer and distant metastasis. Oral Oncol 71:54–59. https://doi.org/10.1016/j.oraloncology.2017.05.017

    Article  PubMed  Google Scholar 

  19. Kim HR, Lee CG, Choi EC, Kim JH, Koh YW, Cho BC (2016) Induction docetaxel and S-1 followed by concomitant radiotherapy with low-dose daily cisplatin in locally advanced head and neck carcinoma. Head Neck 38(Suppl 1):E1653–E1659. https://doi.org/10.1002/hed.24294

    Article  PubMed  Google Scholar 

  20. Namikawa T, Tsuda S, Fujisawa K, Iwabu J, Uemura S, Tsujii S, Maeda H, Kitagawa H, Kobayashi M, Hanazaki K (2018) Conversion surgery after S-1 plus oxaliplatin combination chemotherapy for advanced gastric cancer with multiple liver metastases. Clin J Gastroenterol. https://doi.org/10.1007/s12328-018-0842-8

  21. Ohnuma H, Sato Y, Hirakawa M, Kikuchi S, Miyanishi K, Sagawa T, Takahashi Y, Nobuoka T, Okamoto K, Miyamoto H, Takemasa I, Takayama T, Kato J (2018) Docetaxel, cisplatin and S-1 (DCS) combination chemotherapy for gastric cancer patients with peritoneal metastasis: a retrospective study. Cancer Chemother Pharmacol 81(3):539–548. https://doi.org/10.1007/s00280-018-3523-x

    Article  CAS  PubMed  Google Scholar 

  22. Kim IH, Park SS, Lee CM, Kim MC, Kwon IK, Min JS, Kim HI, Lee HH, Lee SI, Chae H (2018) Efficacy of adjuvant S-1 versus XELOX chemotherapy for patients with gastric Cancer after D2 lymph node dissection: a retrospective, multi-center observational study. Ann Surg Oncol. https://doi.org/10.1245/s10434-018-6375-z

  23. Kagawa S, Muraoka A, Kambara T, Nakayama H, Hamano R, Tanaka N, Noma K, Tanakaya K, Kishimoto H, Shigeyasu K, Kuroda S, Kikuchi S, Kuwada K, Nishizaki M, Shirakawa Y, Fujiwara T (2018) A multi-institution phase II study of docetaxel and S-1 in combination with trastuzumab for HER2-positive advanced gastric cancer (DASH study). Cancer Chemother Pharmacol 81(2):387–392. https://doi.org/10.1007/s00280-017-3505-4

    Article  CAS  PubMed  Google Scholar 

  24. Kim MJ, Kong SY, Nam BH, Kim S, Park YI, Park SR (2018) A randomized phase II study of S-1 versus capecitabine as first-line chemotherapy in elderly metastatic gastric cancer patients with or without poor performance status: clinical and pharmacogenetic results. Pharmacogenet Genomics 28(1):23–30. https://doi.org/10.1097/FPC.0000000000000320

    Article  CAS  PubMed  Google Scholar 

  25. Namikawa T, Maeda H, Kitagawa H, Oba K, Tsuji A, Yoshikawa T, Kobayashi M, Hanazaki K (2018) Treatment using oxaliplatin and S-1 adjuvant chemotherapy for pathological stage III gastric cancer: a multicenter phase II study (TOSA trial) protocol. BMC Cancer 18(1):186. https://doi.org/10.1186/s12885-018-4109-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kuyama S, Ochi N, Bessho A, Hotta K, Ikeda G, Kishino D, Kubo T, Harada D, Fujimoto N, Nakanishi M, Umeno T, Okada T, Chikamori K, Yamagishi T, Ohashi K, Ichihara E, Takigawa N, Tanimoto M, Kiura K (2017) A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor: the Okayama lung Cancer study group trial 1202. Lung Cancer 112:188–194. https://doi.org/10.1016/j.lungcan.2017.08.010

    Article  PubMed  Google Scholar 

  27. Okuda K, Yano M, Tatematsu T, Nakamae K, Yamada T, Kasugai T, Nishida T, Sano M, Moriyama S, Haneda H, Kawano O, Nakanishi R (2018) S-1 vs. paclitaxel plus carboplatin as adjuvant chemotherapy for completely resected stage II/IIIA non-small-cell lung cancer. Mol Clin Oncol 8(1):73–79. https://doi.org/10.3892/mco.2017.1481

    Article  PubMed  Google Scholar 

  28. Sasaki Y, Iwasa S, Okazaki S, Goto M, Kojima Y, Naganuma A, Nagashima K, Nagai Y, Hirano H, Honma Y, Takashima A, Kato K, Hamaguchi T (2018) A phase II study of combination therapy with oral S-1 and cisplatin in elderly patients with advanced gastric cancer. Gastric Cancer 21(3):439–445. https://doi.org/10.1007/s10120-017-0753-2

    Article  CAS  PubMed  Google Scholar 

  29. Ke LR, Xia WX, Qiu WZ, Huang XJ, Yang J, Yu YH, Liang H, Liu GY, Ye YF, Xiang YQ, Guo X, Lv X (2017) Safety and efficacy of lobaplatin combined with 5-fluorouracil as first-line induction chemotherapy followed by lobaplatin-radiotherapy in locally advanced nasopharyngeal carcinoma: preliminary results of a prospective phase II trial. BMC Cancer 17(1):134. https://doi.org/10.1186/s12885-017-3080-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Peng H, Tang LL, Liu X, Chen L, Li WF, Mao YP, Zhang Y, Liu LZ, Tian L, Guo Y, Sun Y, Ma J (2018) Anti-EGFR targeted therapy delivered before versus during radiotherapy in locoregionally advanced nasopharyngeal carcinoma: a big-data, intelligence platform-based analysis. BMC Cancer 18(1):323. https://doi.org/10.1186/s12885-018-4268-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee N, Harris J, Garden AS, Straube W, Glisson B, Xia P, Bosch W, Morrison WH, Quivey J, Thorstad W, Jones C, Ang KK (2009) Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol 27(22):3684–3690. https://doi.org/10.1200/JCO.2008.19.9109

    Article  PubMed  PubMed Central  Google Scholar 

  32. Tang C, Wu F, Wang R, Lu H, Li G (2016) Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial. Am J Cancer Res 6(9):2064–2075

  33. Wu M, Ou D, He X, Hu C (2017) Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. Oral Oncol 73:118–123. https://doi.org/10.1016/j.oraloncology.2017.08.016

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

    Tao Lv, Yujie Wang, Dan Ou, Peiyao Liu & Xiaoshen Wang

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Tao Lv, Yujie Wang, Dan Ou, Peiyao Liu & Xiaoshen Wang

  3. Department of Radiation Oncology, the First Affiliated Hospital of Suzhou University, Suzhou, 215006, China

    Songbing Qin

  4. Department of Radiation Oncology, Taizhou Cancer Hospital, Wenling, 318000, China

    Lidan Liu

  5. Center of Chemoradio-oncology, Ningbo First Hospital, Ningbo City, 315010, China

    Pengrong Lou

Authors
  1. Tao Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yujie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dan Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peiyao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Songbing Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lidan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pengrong Lou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaoshen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoshen Wang.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethical Committee of Fudan University Shanghai Cancer Center.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lv, T., Wang, Y., Ou, D. et al. IMRT combined with S-1 concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: a prospective phase II study. Invest New Drugs 37, 352–359 (2019). https://doi.org/10.1007/s10637-018-00720-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-018-00720-0

Keywords

Search

Navigation