Nasopharyngeal carcinoma

Section editor
	Michael Gibson, MD, PhD Nashville, TN Twitter: mgibson21212 LinkedIn

26 regimens on this page 38 variants on this page

Guidelines

EHNS/ESMO/ESTRO

• 2012: Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

Locally advanced disease, induction

Cisplatin & Fluorouracil

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CF: Cisplatin & Fluorouracil
PF: Platinol (Cisplatin) & Fluorouracil

Variant #1, 80/4000

Study	Evidence	Comparator	Efficacy
Cao et al. 2017	Phase III (E)	No induction	Seems to have superior DFS

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV once on day 1
• Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 4000 mg/m²)

21-day cycle for 2 cycles

Subsequent treatment

• Cisplatin & RT

References

1. Cao SM, Yang Q, Guo L, Mai HQ, Mo HY, Cao KJ, Qian CN, Zhao C, Xiang YQ, Zhang XP, Lin ZX, Li WX, Liu Q, Qiu F, Sun R, Chen QY, Huang PY, Luo DH, Hua YJ, Wu YS, Lv X, Wang L, Xia WX, Tang LQ, Ye YF, Chen MY, Guo X, Hong MH. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:14-23. Epub 2017 Feb 16. link to original article contains protocol PubMed

DCF

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DCF: Docetaxel, Cisplatin, Fluorouracil
TPF: Taxotere (Docetaxel), Platinol (Cisplatin), Fluorouracil

Variant #1, 60/60/3000

Study	Evidence	Comparator	Efficacy
Sun et al. 2016	Phase III (E)	No induction	Seems to have superior FFS

Chemotherapy

• Docetaxel (Taxotere) 60 mg/m² IV once on day 1
• Cisplatin (Platinol) 60 mg/m² IV once on day 1
• Fluorouracil (5-FU) 600 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 3000 mg/m²)

21-day cycle for 3 cycles

Subsequent treatment

• Cisplatin & RT

Variant #2, 70/75/4000

Study	Evidence
Bae et al. 2010	Phase II

This study only involved patients with locoregionally advanced nasopharyngeal cancer.

Chemotherapy

• Docetaxel (Taxotere) 70 mg/m² in 300 mL normal saline IV over 60 minutes once on day 1, given first
• Cisplatin (Platinol) 75 mg/m² IV over 3 hours once on day 1, given second
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 4 days on days 1 to 4, started after completion of cisplatin (total dose per cycle: 4000 mg/m²)

Supportive medications

• Dexamethasone (Decadron) 20 mg IV once 30 minutes prior to Docetaxel (Taxotere)
• Ranitidine (Zantac) 50 mg IV once 30 minutes prior to Docetaxel (Taxotere)
• Chlorpheniramine (Chlor-Trimeton) 5 mg IV once 30 minutes prior to Docetaxel (Taxotere)
• Posthydration after Cisplatin (Platinol) with normal saline (volume/rate not specified)
• Ondansetron (Zofran) 8 mg IV "was routinely given"
• Levofloxacin (Levaquin) 500 mg PO once per day on days 5 to 10 as prophylaxis
• Prophylactic G-CSF per physician's discretion

21-day cycle for 3 cycles

Subsequent treatment

• Cisplatin & RT

References

1. Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, Chung WK, Chung IJ. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010 Feb;65(3):589-95. link to original article contains verified protocol PubMed
2. Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. Epub 2016 Sep 26. link to original article contains verified protocol PubMed

No induction

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Regimen

Study	Evidence	Comparator	Efficacy
Sun et al. 2016	Phase III (C)	TPF	Seems to have inferior FFS

No therapy given prior to definitive chemoradiotherapy.

Subsequent treatment

• Cisplatin & RT

References

1. Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. Epub 2016 Sep 26. link to original article contains verified protocol PubMed
2. Cao SM, Yang Q, Guo L, Mai HQ, Mo HY, Cao KJ, Qian CN, Zhao C, Xiang YQ, Zhang XP, Lin ZX, Li WX, Liu Q, Qiu F, Sun R, Chen QY, Huang PY, Luo DH, Hua YJ, Wu YS, Lv X, Wang L, Xia WX, Tang LQ, Ye YF, Chen MY, Guo X, Hong MH. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:14-23. Epub 2017 Feb 16. link to original article contains protocol PubMed

Locally advanced disease, definitive chemoradiotherapy

Carboplatin & RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Chitapanarux et al. 2007	Phase III	Cisplatin & RT, then CF	Seems not superior

Chemoradiotherapy

• Carboplatin (Paraplatin) 100 mg/m² IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
• Concurrent radiation therapy to the primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

7-week course

Treatment followed in 4 weeks by carboplatin & fluorouracil consolidation.

References

1. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed

Cisplatin & RT

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Cisplatin & RT: Cisplatin & Radiation Therapy

Variant #1, 40 mg/m² weekly dosing

Study	Evidence	Comparator	Efficacy
Chan et al. 2005	Phase III (E)	Radiation therapy	Might have superior OS
Chen et al. 2011	Non-randomized portion of RCT

Chemoradiotherapy

• Cisplatin (Platinol) 40 mg/m² in 1 liter normal saline IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, 43
• Concurrent radiation therapy, 2 Gy fractions x 33 fractions (total dose: 66 Gy), given 5 times per week over 6.5 weeks. See Chan et al. 2005 for additional information about boost doses.

One course

Subsequent treatment

• Chen et al. 2011: CF versus no further treatment

Variant #2, 100 mg/m² x 2

Study	Evidence
Bae et al. 2010	Phase II

Chemoradiotherapy

• Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 22
• Concurrent radiation therapy: 1.8 to 2 Gy fractions (total dose: 68.4 Gy), given 5 times per week

One course

Variant #3, 100 mg/m² x 3

Study	Evidence	Comparator	Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	Phase III (E)	Radiation therapy	Superior OS
Wee et al. 2005	Phase III (E)	Radiation therapy	Superior OS
Chitapanarux et al. 2007	Phase III	Carboplatin & RT, then Carboplatin & 5-FU	Seems not superior
Lee et al. 2010 (NPC-9901)	Phase III (E)	Radiation therapy	Seems to have superior OS (*)
Sun et al. 2016	Non-randomized portion of RCT
Tang et al. 2018	Phase III (C)	Nedaplatin & RT	Non-inferior PFS at 2 y

Intergroup 0099 involved patients with stage III and IV nasopharynx cancers without evidence of metastases. Efficacy for NPC-9901 is based on the 2016 update.

Chemoradiotherapy

• Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
  • Wee et al. 2005 gave 25 mg/m² IV once per day on days 1 to 4, 22 to 25, 43 to 46
• Concurrent radiation therapy with one of the following:
  • Intergroup 0099: 1.8 to 2 Gy fractions x 35 to 39 fractions to the primary tumor (total dose: 70 Gy), given 5 times per week. Minimum total dose to neck nodes is 50 Gy for N0 disease; 66 Gy for nodes less than or equal to 2 cm in size; 70 Gy for nodes greater than 2 cm.
  • Chitapanarux et al. 2007: 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
  • Sun et al. 2016: see paper for details

Supportive medications

• Best described by Al-Sarraf et al. 1998
• Forced hydration: 5% dextrose in 1/2 normal saline with 40 mEq KCl, 2000 mL IV continuous infusion over 24 hours given twice, before each dose of Cisplatin (Platinol) and after the second mannitol infusion
• Mannitol 12.5 g IV bolus prior to Cisplatin (Platinol)
• 5% dextrose in 1/2 normal saline with 30 mEq KCl and mannitol 25 g, 1000 mL IV over 4 hours immediately after Cisplatin (Platinol)
• Antiemetic such as Prochlorperazine (Compazine) 25 mg rectal suppository given 30 minutes prior to Cisplatin (Platinol); Prochlorperazine (Compazine) 10 mg IM every 4 hours as needed for nausea after Cisplatin (Platinol)

One course

Subsequent treatment

• Most studies: Adjuvant CF

References

1. Intergroup 0099: Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. link to original article contains verified protocol PubMed
2. Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. link to original article contains verified protocol PubMed
3. Wee J, Tan EH, Tai BC, Wong HB, Leong SS, Tan T, Chua ET, Yang E, Lee KM, Fong KW, Tan HS, Lee KS, Loong S, Sethi V, Chua EJ, Machin D. 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 Sep 20;23(27):6730-8. link to original article PubMed
4. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed
5. Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, Chung WK, Chung IJ. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010 Feb;65(3):589-95. link to original article contains verified protocol PubMed
6. NPC-9901: 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. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010 Aug 4;102(15):1188-98. Epub 2010 Jul 15. link to original article contains partial protocol PubMed
   1. Update: 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. 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. 2017 Nov 1;123(21):4147-4157. Epub 2017 Jun 29. link to original article PubMed
7. Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. Epub 2011 Dec 7. link to original article contains protocol PubMed
   1. Update: Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:150-158. Epub 2017 Feb 22. link to original article PubMed
8. Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Nov;17(11):1509-1520. Epub 2016 Sep 26. link to original article contains verified protocol PubMed
9. Cao SM, Yang Q, Guo L, Mai HQ, Mo HY, Cao KJ, Qian CN, Zhao C, Xiang YQ, Zhang XP, Lin ZX, Li WX, Liu Q, Qiu F, Sun R, Chen QY, Huang PY, Luo DH, Hua YJ, Wu YS, Lv X, Wang L, Xia WX, Tang LQ, Ye YF, Chen MY, Guo X, Hong MH. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:14-23. Epub 2017 Feb 16. link to original article PubMed
10. Tang LQ, Chen DP, Guo L, Mo HY, Huang Y, Guo SS, Qi B, Tang QN, Wang P, Li XY, Li JB, Liu Q, Gao YH, Xie FY, Liu LT, Li Y, Liu SL, Xie HJ, Liang YJ, Sun XS, Yan JJ, Wu YS, Luo DH, Huang PY, Xiang YQ, Sun R, Chen MY, Lv X, Wang L, Xia WX, Zhao C, Cao KJ, Qian CN, Guo X, Hong MH, Nie ZQ, Chen QY, Mai HQ. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2018 Apr;19(4):461-473. Epub 2018 Feb 28. link to original article contains protocol PubMed

Oxaliplatin & RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Zhang et al. 2005	Phase III	RT	Seems to have superior OS (*)

Note: Reported efficacy is based on the 2013 update.

Chemoradiotherapy

• Oxaliplatin (Eloxatin) 70 mg/m² IV once per week (6 doses)
• Concurrent radiation therapy to primary tumor (70 to 74 Gy).

6-week course

References

1. Zhang L, Zhao C, Peng PJ, Lu LX, Huang PY, Han F, Wu SX. Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol. 2005 Nov 20;23(33):8461-8. Epub 2005 Oct 17. link to original article contains verified protocol PubMed
   1. Update: Wu X, Huang PY, Peng PJ, Lu LX, Han F, Wu SX, Hou X, Zhao HY, Huang Y, Fang WF, Zhao YY, Xue C, Hu ZH, Zhang J, Zhang JW, Ma YX, Liang WH, Zhao C, Zhang L. Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma. Ann Oncol. 2013 Aug;24(8):2131-6. Epub 2013 May 9. link to original article PubMed

Radiation therapy

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Regimen

Study	Evidence	Comparator	Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	Phase III (C)	Cisplatin & RT, then CF	Inferior OS
Chan et al. 2005	Phase III (C)	Cisplatin & RT	Might have inferior OS
Wee et al. 2005	Phase III (C)	Cisplatin & RT	Inferior OS
Lee et al. 2010 (NPC-9901)	Phase III (C)	Cisplatin & RT	Seems to have inferior OS (*)

Efficacy for NPC-9901 is based on the 2016 update. Here for reference purposes.

Radiotherapy

• External beam radiotherapy

References

1. Intergroup 0099: Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. link to original article contains verified protocol PubMed
2. Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. link to original article contains verified protocol PubMed
3. Wee J, Tan EH, Tai BC, Wong HB, Leong SS, Tan T, Chua ET, Yang E, Lee KM, Fong KW, Tan HS, Lee KS, Loong S, Sethi V, Chua EJ, Machin D. 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 Sep 20;23(27):6730-8. link to original article PubMed
4. Zhang L, Zhao C, Peng PJ, Lu LX, Huang PY, Han F, Wu SX. Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol. 2005 Nov 20;23(33):8461-8. Epub 2005 Oct 17. link to original article contains verified protocol PubMed
   1. Update: Wu X, Huang PY, Peng PJ, Lu LX, Han F, Wu SX, Hou X, Zhao HY, Huang Y, Fang WF, Zhao YY, Xue C, Hu ZH, Zhang J, Zhang JW, Ma YX, Liang WH, Zhao C, Zhang L. Long-term follow-up of a phase III study comparing radiotherapy with or without weekly oxaliplatin for locoregionally advanced nasopharyngeal carcinoma. Ann Oncol. 2013 Aug;24(8):2131-6. Epub 2013 May 9. link to original article PubMed
5. NPC-9901: 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. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010 Aug 4;102(15):1188-98. Epub 2010 Jul 15. link to original article contains partial protocol PubMed
   1. Update: 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. 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. 2017 Nov 1;123(21):4147-4157. Epub 2017 Jun 29. link to original article PubMed

Adjuvant therapy

Carboplatin & Fluorouracil

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Regimen

Study	Evidence
Chitapanarux et al. 2007	Non-randomized portion of RCT

Preceding treatment

• Carboplatin & RT

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 IV once on day 1
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 cycles

References

1. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed

Cisplatin & Fluorouracil

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Cisplatin and Fluorouracil

Variant #1, 80/4000, 4 days of 5-FU

Study	Evidence	Comparator	Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	Non-randomized portion of RCT
Wee et al. 2005	Non-randomized portion of RCT
Chitapanarux et al. 2007	Phase III	Carboplatin & RT, then Carboplatin & 5-FU	Seems not superior
Lee et al. 2010 (NPC-9901))	Non-randomized portion of RCT

Preceding treatment

• Intergroup 0099 & Wee et al. 2005: Cisplatin & RT versus RT
• Chitapanarux et al. 2007 & NPC-9901: Cisplatin & RT

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV over 15 to 20 minutes once on day 1
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 cycles

Variant #2, 80/4000, 5 days of 5-FU

Study	Evidence	Comparator	Efficacy
Chen et al. 2011	Phase III	No further treatment	Seems not superior

Preceding treatment

• Cisplatin & RT

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV once on day 1
• Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 cycles

References

1. Intergroup 0099: Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. link to original article contains verified protocol PubMed
2. Wee J, Tan EH, Tai BC, Wong HB, Leong SS, Tan T, Chua ET, Yang E, Lee KM, Fong KW, Tan HS, Lee KS, Loong S, Sethi V, Chua EJ, Machin D. 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 Sep 20;23(27):6730-8. link to original article contains protocol PubMed
3. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed
4. NPC-9901: 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. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010 Aug 4;102(15):1188-98. Epub 2010 Jul 15. link to original article contains partial protocol PubMed
   1. Update: 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. 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. 2017 Nov 1;123(21):4147-4157. Epub 2017 Jun 29. link to original article PubMed
5. Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012 Feb;13(2):163-71. Epub 2011 Dec 7. link to original article contains protocol PubMed
   1. Update: Chen L, Hu CS, Chen XZ, Hu GQ, Cheng ZB, Sun Y, Li WX, Chen YY, Xie FY, Liang SB, Chen Y, Xu TT, Li B, Long GX, Wang SY, Zheng BM, Guo Y, Sun Y, Mao YP, Tang LL, Chen YM, Liu MZ, Ma J. Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial. Eur J Cancer. 2017 Apr;75:150-158. Epub 2017 Feb 22. link to original article PubMed

Recurrent or metastatic disease

Cisplatin & Fluorouracil

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CF: Cisplatin and Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Zhang et al. 2016	Phase III	Cisplatin & Gemcitabine	Inferior PFS

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV once on day 1
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m²)

21-day cycle for up to 6 cycles

References

1. Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. Epub 2016 Aug 23. link to original article contains protocol PubMed

Cisplatin & Gemcitabine

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Regimen

Study	Evidence	Comparator	Efficacy
Zhang et al. 2016	Phase III	CF	Superior PFS

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV once on day 1
• Gemcitabine (Gemzar) 1000 mg/m²/day IV once per day on days 1 & 8

21-day cycle for up to 6 cycles

References

1. Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. Epub 2016 Aug 23. link to original article contains protocol PubMed

Gemcitabine monotherapy

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Regimen

Study	Evidence
Zhang et al. 2008	Phase II

This study only involved patients who had already received previous platinum-based chemotherapy.

Chemotherapy

• Gemcitabine (Gemzar) 1000 mg/m² in 100 mL normal saline IV over 30 minutes once per day on days 1, 8, 15

Supportive medications

• 5-HT3 receptor antagonists prior to chemotherapy
• G-CSF and GM-CSF were not used

28-day cycles

References

1. Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008 Jan;61(1):33-8. Epub 2007 Mar 20. link to original article contains verified protocol PubMed