Nasopharyngeal carcinoma

Section editor
	Michael K. Gibson, MD, PhD, FACP Vanderbilt University Nashville, TN mgibson21212 LinkedIn

26 regimens on this page 38 variants on this page

Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: this page has regimens specific to nasopharyngeal carcinoma; more general regimens are available on the head and neck cancer page.

Guidelines

ASCO/CSCO

• 2021: Chen et al. Chemotherapy in Combination With Radiotherapy for Definitive-Intent Treatment of Stage II-IVA Nasopharyngeal Carcinoma: CSCO and ASCO Guideline

EHNS/ESMO/ESTRO

• 2012: Chan et al. Nasopharyngeal cancer: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up

ESMO/EURACAN

• 2021: Bossi et al. Nasopharyngeal carcinoma: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up

NCCN

• NCCN Guidelines - Head and Neck Cancers

Locally advanced disease, induction

Cisplatin & Epirubicin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chua et al. 1998 (AOCOA)	1989-1993	Phase 3 (E-esc)	No induction	Might have superior OS1

¹Reported efficacy is based on the 2005 pooled update.

Chemotherapy

• Cisplatin (Platinol)
• Epirubicin (Ellence)

Subsequent treatment

• RT

References

1. AOCOA: Chua DT, Sham JS, Choy D, Lorvidhaya V, Sumitsawan Y, Thongprasert S, Vootiprux V, Cheirsilpa A, Azhar T, Reksodiputro AH; Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group. Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Cancer. 1998 Dec 1;83(11):2270-83. link to original article PubMed
   1. Pooled update: Chua DT, Ma J, Sham JS, Mai HQ, Choy DT, Hong MH, Lu TX, Min HQ. Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: a pooled data analysis of two phase III trials. J Clin Oncol. 2005 Feb 20;23(6):1118-24. Epub 2005 Jan 18. link to original article PubMed

Cisplatin & Fluorouracil (CF)

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

Regimen variant #1, 80/4000 x 2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cao et al. 2017 (RDDA2017000111)	2008-2015	Phase 3 (E-esc)	No induction	Seems to have superior OS1OS60: 80.8% vs 76.8%

¹Reported efficacy is based on the 2019 update.

Chemotherapy

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

21-day cycle for 2 cycles

Subsequent treatment

• Cisplatin & RT

Regimen variant #2, 100/4000 x 2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lv et al. 2021	2013-2015	Phase 3 (C)	Lobaplatin & Fluorouracil	Non-inferior PFS60

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1
• Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

21-day cycle for 2 cycles

Subsequent treatment

• Cisplatin & RT

Regimen variant #3, 100/4000 x 3

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Jin et al. 2019 (ESNCCT)	2012-2014	Phase 3 (C)	TPF	Inconclusive whether non-inferior PFS
Li et al. 2022 (SYSUCC 20160049)	2016-2019	Phase 3 (C)	TPC	Inferior FFS

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1
• Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

21-day cycle for 3 cycles

Subsequent treatment

• Cisplatin & RT

Regimen variant #4, 100/5000 x 6

Study	Years of enrollment	Evidence
You et al. 2020 (SYSUCC 5010)	2013-NR in abstract	Non-randomized portion of phase 3 RCT

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m²)

21-day cycle for 6 cycles

Subsequent treatment

• RT consolidation versus no further treatment

References

1. RDDA2017000111: 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 NCT00705627
   1. Update: Yang Q, Cao SM, Guo L, Hua YJ, Huang PY, Zhang XL, Lin M, You R, Zou X, Liu YP, Xie YL, Wang ZQ, Mai HQ, Chen QY, Tang LQ, Mo HY, Cao KJ, Qian CN, Zhao C, Xiang YQ, Zhang XP, Lin ZX, Li WX, Liu Q, Li JB, Ling L, Guo X, Hong MH, Chen MY. Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: long-term results of a phase III multicentre randomised controlled trial. Eur J Cancer. 2019 Sep;119:87-96. Epub 2019 Aug 16. link to original article PubMed
2. ESNCCT: Jin T, Qin WF, Jiang F, Jin QF, Wei QC, Jia YS, Sun XN, Li WF, Chen XZ. Cisplatin and Fluorouracil Induction Chemotherapy With or Without Docetaxel in Locoregionally Advanced Nasopharyngeal Carcinoma. Transl Oncol. 2019 Apr;12(4):633-639. Epub 2019 Feb 20. link to original article link PMC article contains dosing details in manuscript PubMed NCT01536223
3. SYSUCC 5010: You R, Liu YP, Huang PY, Zou X, Sun R, He YX, Wu YS, Shen GP, Zhang HD, Duan CY, Tan SH, Cao JY, Li JB, Xie YL, Zhang YN, Wang ZQ, Yang Q, Lin M, Jiang R, Zhang MX, Hua YJ, Tang LQ, Zhuang AH, Chen QY, Guo L, Mo HY, Chen Y, Mai HQ, Ling L, Liu Q, Chua MLK, Chen MY. Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1345-1352. link to original article link to PMC article contains protocol PubMed NCT02111460
4. Lv X, Cao X, Xia WX, Liu KY, Qiang MY, Guo L, Qian CN, Cao KJ, Mo HY, Li XM, Li ZH, Han F, He YX, Liu YM, Wu SX, Bai YR, Ke LR, Qiu WZ, Liang H, Liu GY, Miao JJ, Li WZ, Lv SH, Chen X, Zhao C, Xiang YQ, Guo X. Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):716-726. Epub 2021 Apr 12. link to original article contains protocol PubMed ChiCTR-TRC-13003285
5. SYSUCC 20160049: Li WZ, Lv X, Hu D, Lv SH, Liu GY, Liang H, Ye YF, Yang W, Zhang HX, Yuan TZ, Wang DS, Lu N, Ke LR, Tang WB, Tong LH, Chen ZJ, Liu T, Cao KJ, Mo HY, Guo L, Zhao C, Chen MY, Chen QY, Huang PY, Sun R, Qiu F, Luo DH, Wang L, Hua YJ, Tang LQ, Qian CN, Mai HQ, Guo X, Xiang YQ, Xia WX. Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 May 1;8(5):706-714. link to original article contains protocol link to PMC article PubMed NCT02940925

Cisplatin & Gemcitabine (GC)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Zhang et al. 2019 (B2013-022-01)	2013-2016	Phase 3 (E-esc)	No induction	Superior OS1 OS60: 87.9% vs 78.8% (HR 0.51, 95% CI 0.34-0.78)

¹Reported efficacy is based on the 2022 update.

Chemotherapy

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

21-day cycle for 3 cycles

Subsequent treatment

• Cisplatin & RT

References

1. B2013-022-01: Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. Epub 2019 May 31. link to original article contains protocol PubMed NCT01872962
   1. Update: Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Xie FY, Sun Y, Ma J, Tang LL. Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial. J Clin Oncol. 2022 Aug 1;40(22):2420-2425. Epub 2022 Jun 16. link to original article PubMed

DCF

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

Regimen variant #1, 60/60/3000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Sun et al. 2016 (YP2010171)	2011-2013	Phase 3 (E-esc)	No induction	Seems to have superior OS1 OS60: 85.6% vs 77.7% (HR 0.65, 95% CI 0.43-0.98)

¹Reported efficacy for YP2010171 is based on the 2019 update.

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, started on day 1 (total dose per cycle: 3000 mg/m²)

21-day cycle for 3 cycles

Subsequent treatment

• Cisplatin & RT

Regimen variant #2, 70/75/4000

Study	Evidence
Bae et al. 2010	Phase 2

This study only involved patients with locoregionally advanced nasopharyngeal cancer.

Chemotherapy

• Docetaxel (Taxotere) 70 mg/m² 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 96 hours, started on day 1, given third (total dose per cycle: 4000 mg/m²)

Supportive medications

• Dexamethasone (Decadron) 20 mg IV once on day 1; 30 minutes prior to Docetaxel (Taxotere)
• Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to Docetaxel (Taxotere)
• Chlorpheniramine (Chlor-Trimeton) 5 mg IV once on day 1; 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
• 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 dosing details in manuscript PubMed
2. YP2010171: 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 dosing details in manuscript PubMed NCT01245959
   1. Update: 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, Sun Y. Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: long-term results of phase 3 randomized controlled trial. Int J Cancer. 2019 Jul 1;145(1):295-305. Epub 2019 Jan 24. link to original article PubMed
3. ESNCCT: Jin T, Qin WF, Jiang F, Jin QF, Wei QC, Jia YS, Sun XN, Li WF, Chen XZ. Cisplatin and Fluorouracil Induction Chemotherapy With or Without Docetaxel in Locoregionally Advanced Nasopharyngeal Carcinoma. Transl Oncol. 2019 Apr;12(4):633-639. Epub 2019 Feb 20. link to original article link PMC article contains dosing details in manuscript PubMed NCT01536223

TPC

TPC: Taxol (Paclitaxel), Platinol (Cisplatin), Capecitabine

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Li et al. 2022 (SYSUCC 20160049)	2016-2019	Phase 3 (E-esc)	PF	Superior FFS FFS36: 83.5% vs 68.9% (HR 0.47, 95% CI 0.28-0.79)

Chemotherapy

• Paclitaxel (Taxol) 150 mg/m² IV once on day 1
• Cisplatin (Platinol) 60 mg/m² IV once on day 1
• Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 2 cycles

Subsequent treatment

• Chemoradiotherapy

References

1. SYSUCC 20160049: Li WZ, Lv X, Hu D, Lv SH, Liu GY, Liang H, Ye YF, Yang W, Zhang HX, Yuan TZ, Wang DS, Lu N, Ke LR, Tang WB, Tong LH, Chen ZJ, Liu T, Cao KJ, Mo HY, Guo L, Zhao C, Chen MY, Chen QY, Huang PY, Sun R, Qiu F, Luo DH, Wang L, Hua YJ, Tang LQ, Qian CN, Mai HQ, Guo X, Xiang YQ, Xia WX. Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 May 1;8(5):706-714. link to original article contains protocol link to PMC article PubMed NCT02940925

Locally advanced disease, definitive chemoradiotherapy

Carboplatin & RT

Carboplatin & RT: Carboplatin & Radiation Therapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chitapanarux et al. 2007	1999-2004	Phase 3 (E-switch-ic)	Cisplatin & RT, then CF	Seems to have non-inferior OS36

Chemotherapy

• Carboplatin (Paraplatin) 100 mg/m² IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36

Radiotherapy

• Concurrent radiation therapy to the primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy)

7-week course

Subsequent treatment

• Carboplatin & fluorouracil consolidation, after 4 weeks

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 dosing details in manuscript PubMed

Cisplatin & RT

Cisplatin & RT: Cisplatin & Radiation Therapy

Regimen variant #1, 30 mg/m² weekly dosing

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chen et al. 2011	2003-2007	Phase 3 (E-esc)	Radiation therapy	Superior OS OS60: 94.5% vs 85.8% (HR 0.30, 95% CI 0.12-0.76)

Chemotherapy

• Cisplatin (Platinol) 30 mg/m² IV once per day on days 1, 8, 15, 22, 29, 36, 43

Radiotherapy

• Concurrent radiation therapy, 2 Gy x 34 to 35 fractions (total dose of 68 to 70 Gy)

7-week course

Regimen variant #2, 40 mg/m² weekly dosing

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chan et al. 2002	1994-1999	Phase 3 (E-esc)	Radiation therapy	Might have superior OS1
Tan et al. 2015	2004-2012	Non-randomized portion of phase 2/3 RCT
Chen et al. 2011 (YP2008004)	2006-2010	Non-randomized portion of RCT

¹Reported efficacy for Chan et al. 2002 is based on the 2005 update.

Preceding treatment

• Tan et al. 2015: GCP x 3 versus no induction therapy

Chemotherapy

• Cisplatin (Platinol) 40 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, 43

Radiotherapy

• Concurrent radiation therapy, 2 Gy fractions x 33 fractions (total dose: 66 Gy). See Chan et al. 2005 for additional information about boost doses.

6.5-week course

Subsequent treatment

• YP2008004: CF versus no further treatment

Regimen variant #3, 40 mg/m² weekly dosing x 6

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Xia et al. 2021	2011-2016	Phase 3 (C)	Cisplatin & RT; q3wk x 2	Non-inferior FFS

Chemotherapy

• Cisplatin (Platinol) 40 mg/m² IV over 2 hours once on day 1

7-day cycle for 6 cycles

Radiotherapy

• Concurrent radiation therapy

Regimen variant #4, 100 mg/m² x 2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bae et al. 2010	2004-2008	Phase 2
Xia et al. 2021	2011-2016	Phase 3 (E-switch-ic)	Cisplatin & RT; weekly x 6	Non-inferior FFS

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1

21-day cycle for 2 cycles

Radiotherapy

• Concurrent radiation therapy: 1.8 to 2 Gy fractions (total dose: 68.4 Gy)

5.5-week course

Regimen variant #5, 100 mg/m² x 3

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	1989-1995	Phase 3 (E-esc)	Radiation therapy	Superior OS
Wee et al. 2005	1997-2003	Phase 3 (E-esc)	Radiation therapy	Superior OS OS36: 85% vs 80% (HR 0.51, 95% CI 0.31-0.81)
Chitapanarux et al. 2007	1999-2004	Phase 3 (C)	Carboplatin & RT, then Carboplatin & 5-FU	Seems to have non-inferior OS36
Lee et al. 2010 (NPC-9901)	1999-2004	Phase 3 (E-esc)	Radiation therapy	Seems to have superior OS1OS120: 62% vs 49% (HR 0.74, 95% CI 0.56-1.00)
Tang et al. 2018	2004-2012	Phase 3 (C)	Nedaplatin & RT	Non-inferior PFS at 2 y
Sun et al. 2016 (YP2010171)	2011-2013	Non-randomized portion of RCT
Tang et al. 2022 (SYSUCC IRNPC15)	2015-2020	Phase 3 (C)	Cisplatin & RT	Non-inferior FFS

¹Reported efficacy for NPC-9901 is based on the 2016 update.
Note: Intergroup 0099 involved patients with stage III and IV nasopharynx cancers without evidence of metastases.

Chemotherapy

• Cisplatin (Platinol) 100 mg/m² IV once on day 1
  • Wee et al. 2005 gave 25 mg/m² IV once per day on days 1 to 4

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 once on day 1, 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 once on day 1; 30 minutes prior to Cisplatin (Platinol)
• Prochlorperazine (Compazine) 10 mg IM every 4 hours as needed for nausea after Cisplatin (Platinol)

21-day cycle for 3 cycles

Radiotherapy

• 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). 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)
  • YP2010171: see paper for details
  • SYSUCC IRNPC15: IMRT, see paper for details

7-week 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 dosing details in manuscript PubMed
2. Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ. 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 Apr 15;20(8):2038-44. link to original article PubMed
   1. Update: 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript 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 HARECCTR0500023
   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 QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F, Sun R, Deng MQ, Chen MY, Hua YJ, Guo X, Cao KJ, Hong MH, Qian CN, Mai HQ. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011 Dec 7;103(23):1761-70. Epub 2011 Nov 4. link to original article contains protocol PubMed
   1. Update: Li XY, Chen QY, Sun XS, Liu SL, Yan JJ, Guo SS, Liu LT, Xie HJ, Tang QN, Liang YJ, Wen YF, Guo L, Mo HY, Chen MY, Sun Y, Ma J, Tang LQ, Mai HQ. Ten-year outcomes of survival and toxicity for a phase III randomised trial of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma. Eur J Cancer. 2019 Mar;110:24-31. Epub 2019 Feb 7. link to original article PubMed
8. YP2008004: 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 NCT00677118
   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
9. Tan T, Lim WT, Fong KW, Cheah SL, Soong YL, Ang MK, Ng QS, Tan D, Ong WS, Tan SH, Yip C, Quah D, Soo KC, Wee J. Concurrent chemo-radiation with or without induction gemcitabine, Carboplatin, and Paclitaxel: a randomized, phase 2/3 trial in locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2015 Apr 1;91(5):952-60. link to original article contains protocol PubMed
10. YP2010171: 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 dosing details in manuscript PubMed NCT01245959
    1. Update: 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, Sun Y. Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: long-term results of phase 3 randomized controlled trial. Int J Cancer. 2019 Jul 1;145(1):295-305. Epub 2019 Jan 24. link to original article PubMed
11. RDDA2017000111: 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
12. 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 NCT01540136
13. Xia WX, Lv X, Liang H, Liu GY, Sun R, Zeng Q, Li SW, Mo HY, Han F, Luo DH, Liu Q, Shi MY, Ye YF, Yang J, Ke LR, Qiang MY, Qiu WZ, Yu YH, Liu KY, Huang XJ, Li WZ, Lv SH, Cai ZC, Miao JJ, Guo L, Chen MY, Cao KJ, Wang L, Zhao C, Huang PY, Chen QY, Hua YJ, Tang LQ, Qian CN, Mai HQ, Guo X, Xiang YQ. A Randomized Controlled Trial Comparing Two Different Schedules for Cisplatin Treatment in Patients with Locoregionally Advanced Nasopharyngeal Cancer. Clin Cancer Res. 2021 Aug 1;27(15):4186-4194. Epub 2021 Jun 3. link to original article contains protocol PubMed ChiCTR-TRC-12001979
14. SYSUCC IRNPC15: Tang LL, Guo R, Zhang N, Deng B, Chen L, Cheng ZB, Huang J, Hu WH, Huang SH, Luo WJ, Liang JH, Zheng YM, Zhang F, Mao YP, Li WF, Zhou GQ, Liu X, Chen YP, Xu C, Lin L, Liu Q, Du XJ, Zhang Y, Sun Y, Ma J. Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA. 2022 Aug 23;328(8):728-736. link to original article PubMed NCT02633202

Cisplatin & Fluorouracil (CF) & RT

CF & RT: Cisplatin, Fluorouracil, Radiation Therapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lin et al. 2003	1993-1999	Phase 3 (E-esc)	RT	Superior OS

Chemotherapy

• Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 5
• Fluorouracil (5-FU) 400 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1600 mg/m²)

28-day cycle for 2 cycles

Radiotherapy

• Concurrent radiation therapy, total dose 70 to 74 Gy

7- to 8-week course

References

1. Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 2003 Feb 15;21(4):631-7. link to original article contains protocol PubMed

Oxaliplatin & RT

Oxaliplatin & RT: Oxaliplatin & Radiation Therapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Zhang et al. 2005	2001-2003	Phase 3 (E-esc)	RT	Superior OS1 OS84: 71.3% vs 56.3% (HR 0.54, 95% CI 0.31-0.94)

¹Reported efficacy is based on the 2013 update.

Chemotherapy

• Oxaliplatin (Eloxatin) 70 mg/m² IV once per day on days 1, 8, 15, 22, 29, 36

Radiotherapy

• 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 dosing details in manuscript 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

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	1989-1995	Phase 3 (C)	Cisplatin & RT, then CF	Inferior OS
Chan et al. 2002	1994-1999	Phase 3 (C)	Cisplatin & RT	Might have inferior OS1
Wee et al. 2005	1997-2003	Phase 3 (C)	Cisplatin & RT	Inferior OS
Lee et al. 2010 (NPC-9901)	1999-2004	Phase 3 (C)	Cisplatin & RT	Seems to have inferior OS2
Chen et al. 2011	2003-2007	Phase 3 (C)	Cisplatin & RT	Inferior OS
Tang et al. 2022 (SYSUCC IRNPC15)	2015-2020	Phase 3 (E-de-esc)	Cisplatin & RT	Non-inferior FFS FFS36: 90.5% vs 91.9%

¹Reported efficacy for Chan et al. 2002 is based on the 2005 update.
²Reported efficacy for NPC-9901 is based on the 2016 update.

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 dosing details in manuscript PubMed
2. Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, Leung SF, Cheung FY, Yeo W, Yiu HH, Yu KH, Chiu KW, Chan DT, Mok T, Yuen KT, Mo F, Lai M, Kwan WH, Choi P, Johnson PJ. 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 Apr 15;20(8):2038-44. link to original article PubMed
   1. Update: 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 dosing details in manuscript 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 dosing details in manuscript 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 HARECCTR0500023
   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
6. Chen QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F, Sun R, Deng MQ, Chen MY, Hua YJ, Guo X, Cao KJ, Hong MH, Qian CN, Mai HQ. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011 Dec 7;103(23):1761-70. Epub 2011 Nov 4. link to original article contains protocol PubMed
   1. Update: Li XY, Chen QY, Sun XS, Liu SL, Yan JJ, Guo SS, Liu LT, Xie HJ, Tang QN, Liang YJ, Wen YF, Guo L, Mo HY, Chen MY, Sun Y, Ma J, Tang LQ, Mai HQ. Ten-year outcomes of survival and toxicity for a phase III randomised trial of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma. Eur J Cancer. 2019 Mar;110:24-31. Epub 2019 Feb 7. link to original article PubMed
7. SYSUCC 5010: You R, Liu YP, Huang PY, Zou X, Sun R, He YX, Wu YS, Shen GP, Zhang HD, Duan CY, Tan SH, Cao JY, Li JB, Xie YL, Zhang YN, Wang ZQ, Yang Q, Lin M, Jiang R, Zhang MX, Hua YJ, Tang LQ, Zhuang AH, Chen QY, Guo L, Mo HY, Chen Y, Mai HQ, Ling L, Liu Q, Chua MLK, Chen MY. Efficacy and Safety of Locoregional Radiotherapy With Chemotherapy vs Chemotherapy Alone in De Novo Metastatic Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Sep 1;6(9):1345-1352. link to original article link to PMC article PubMed NCT02111460
8. SYSUCC IRNPC15: Tang LL, Guo R, Zhang N, Deng B, Chen L, Cheng ZB, Huang J, Hu WH, Huang SH, Luo WJ, Liang JH, Zheng YM, Zhang F, Mao YP, Li WF, Zhou GQ, Liu X, Chen YP, Xu C, Lin L, Liu Q, Du XJ, Zhang Y, Sun Y, Ma J. Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA. 2022 Aug 23;328(8):728-736. link to original article PubMed NCT02633202

Adjuvant therapy

Capecitabine monotherapy

Regimen variant #1, 8 cycles

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (CCRT-AC-LAHR-NPC)	2014-2018	Phase 3 (E-esc)	Observation	Superior FFS FFS36: 88% vs 73% (HR 0.52, 95% CI 0.29-0.77)

Preceding treatment

• Cisplatin & RT

Chemotherapy

• Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 8 cycles

Regimen variant #2, 12 months

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chen et al. 2021 (2016-FXY-075)	2017-2018	Phase 3 (E-esc)	Observation	Superior FFS FFS36: 85% vs 76% (HR 0.50, 95% CI 0.32-0.79)

Preceding treatment

• Definitive chemoradiotherapy

Chemotherapy

• Capecitabine (Xeloda) 650 mg/m² PO twice per day

12-month course

References

1. 2016-FXY-075: Chen YP, Liu X, Zhou Q, Yang KY, Jin F, Zhu XD, Shi M, Hu GQ, Hu WH, Sun Y, Wu HF, Wu H, Lin Q, Wang H, Tian Y, Zhang N, Wang XC, Shen LF, Liu ZZ, Huang J, Luo XL, Li L, Zang J, Mei Q, Zheng BM, Yue D, Xu J, Wu SG, Shi YX, Mao YP, Chen L, Li WF, Zhou GQ, Sun R, Guo R, Zhang Y, Xu C, Lv JW, Guo Y, Feng HX, Tang LL, Xie FY, Sun Y, Ma J. Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2021 Jun 4:S0140-6736(21)01123-5. Epub ahead of print. link to original article contains protocol PubMed NCT02958111
2. CCRT-AC-LAHR-NPC: NCT02143388

Carboplatin & Fluorouracil

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, started on day 1 (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 dosing details in manuscript PubMed

Cisplatin & Fluorouracil (CF)

Cisplatin and Fluorouracil

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

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	1989-1995	Non-randomized portion of RCT
Wee et al. 2005	1997-2003	Non-randomized portion of RCT
Chitapanarux et al. 2007	1999-2004	Phase 3 (C)	Carboplatin & RT, then Carboplatin & 5-FU	Seems to have non-inferior OS36
Lee et al. 2010 (NPC-9901)	1999-2004	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, started on day 1 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 cycles

Regimen variant #2, 80/4000, 5 days of 5-FU

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Chen et al. 2011 (YP2008004)	2006-2010	Phase 3 (E-esc)	No further treatment	Did not meet primary endpoint of FFS

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, started on day 1 (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 dosing details in manuscript 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 dosing details in manuscript 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 HARECCTR0500023
   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. YP2008004: 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 NCT00677118
   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 (CF)

CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol

Regimen variant #1, 80/4000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Zhang et al. 2016 (GEM20110714)	2012-2015	Phase 3 (C)	Cisplatin & Gemcitabine	Inferior OS1

¹Reported efficacy is based on the 2021 update.
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Chemotherapy

• Cisplatin (Platinol) 80 mg/m² IV once on day 1
• Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m²)

21-day cycle for up to 6 cycles

Regimen variant #2, 100/5000

Study	Evidence
Au & Ang 1994	Non-randomized portion of RCT

Chemotherapy

• Cisplatin (Platinol) 33.3 mg/m² IV once per day on days 1 to 3
• Fluorouracil (5-FU) 1000 mg/m² IV once per day on days 1 to 5

21-day cycles

References

1. Au E, Ang PT. A phase II trial of 5-fluorouracil and cisplatinum in recurrent or metastatic nasopharyngeal carcinoma. Ann Oncol. 1994 Jan;5(1):87-9. link to original article contains protocol PubMed
2. GEM20110714: 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 NCT01528618
   1. Update: Hong S, Zhang Y, Yu G, Peng P, Peng J, Jia J, Wu X, Huang Y, Yang Y, Lin Q, Xi X, 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, Fang W, Zhang L. Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study. J Clin Oncol. 2021 Oct 10;39(29):3273-3282. Epub 2021 Aug 11. link to original article link to PMC article [PubMed

Cisplatin & Gemcitabine (GC)

GP: Gemcitabine & Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Zhang et al. 2016 (GEM20110714)	2012-2015	Phase 3 (E-switch-ic)	CF	Superior OS1 Median OS: 22.1 vs 18.6 mo (HR 0.72, 95% CI 0.58-0.90)
Yang et al. 2021 (CAPTAIN-1st)	2018-2019	Phase 3 (C)	GC & Camrelizumab	Inferior PFS
Mai et al. 2021 (JUPITER-02)	2018-2019	Phase 3 (C)	GC & Toripalimab	Seems to have inferior OS

¹Reported efficacy is based on the 2021 update.

Chemotherapy

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

21-day cycle for up to 6 cycles

References

1. GEM20110714: 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 NCT01528618
   1. Update: Hong S, Zhang Y, Yu G, Peng P, Peng J, Jia J, Wu X, Huang Y, Yang Y, Lin Q, Xi X, 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, Fang W, Zhang L. Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study. J Clin Oncol. 2021 Oct 10;39(29):3273-3282. Epub 2021 Aug 11. link to original article link to PMC article [PubMed
2. CAPTAIN-1st: Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. Epub 2021 Jun 23. link to original article contains protocol PubMed NCT03707509
3. JUPITER-02: Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. Epub 2021 Aug 2. link to original article PubMed NCT03581786

Cisplatin & Gemcitabine (GC) & Camrelizumab

GP & Camrelizumab: Gemcitabine, Platinol (Cisplatin), Camrelizumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Yang et al. 2021 (CAPTAIN-1st)	2018-2019	Phase 3 (E-esc)	GC	Superior PFS Median PFS: 9.7 vs 6.9 mo (HR 0.54, 95% CI 0.39-0.76)

Chemotherapy

• Cisplatin (Platinol) as follows:
  • Cycles 1 up to 6: 80 mg/m² IV once on day 1
• Gemcitabine (Gemzar) as follows:
  • Cycles 1 up to 6: 1000 mg/m² IV once per day on days 1 & 8

Immunotherapy

• Camrelizumab (AiRuiKa) 200 mg IV once on day 1

21-day cycles

References

1. CAPTAIN-1st: Yang Y, Qu S, Li J, Hu C, Xu M, Li W, Zhou T, Shen L, Wu H, Lang J, Hu G, Luo Z, Fu Z, Qu S, Feng W, Chen X, Lin S, Zhang W, Li X, Sun Y, Lin Z, Lin Q, Lei F, Long J, Hong J, Huang X, Zeng L, Wang P, He X, Zhang B, Yang Q, Zhang X, Zou J, Fang W, Zhang L. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1162-1174. Epub 2021 Jun 23. link to original article contains protocol PubMed NCT03707509

Cisplatin & Gemcitabine (GC) & Toripalimab

GC & Toripalimab: Gemcitabine, Cisplatin, Toripalimab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Mai et al. 2021 (JUPITER-02)	2018-2019	Phase 3 (E-esc)	GC	Seems to have superior OS (HR 0.60, 95% CI 0.36-0.997)

Chemotherapy

• Cisplatin (Platinol) as follows:
  • Cycles 1 up to 6: 80 mg/m² IV once on day 1
• Gemcitabine (Gemzar) as follows:
  • Cycles 1 up to 6: 1000 mg/m² IV once per day on days 1 & 8

Immunotherapy

• Toripalimab (Tuoyi) 240 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

1. JUPITER-02: Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, Li J, Shi YR, Jin F, Xu R, Pan J, Qu S, Li P, Hu C, Liu YC, Jiang Y, He X, Wang HM, Lim WT, Liao W, He X, Chen X, Liu Z, Yuan X, Li Q, Lin X, Jing S, Chen Y, Lu Y, Hsieh CY, Yang MH, Yen CJ, Samol J, Feng H, Yao S, Keegan P, Xu RH. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021 Sep;27(9):1536-1543. Epub 2021 Aug 2. link to original article PubMed NCT03581786

Gemcitabine monotherapy

Regimen

Study	Evidence
Zhang et al. 2007	Phase 2

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

Chemotherapy

• Gemcitabine (Gemzar) 1000 mg/m² 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 dosing details in manuscript PubMed
2. KEYNOTE-121: NCT02611960

Maintenance after first-line therapy

Capecitabine monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Liu et al. 2022 (SYSUCC 2015029)	2015-2020	Phase 3 (E-esc)	Best supportive care	Superior PFS Median PFS: 35.9 vs 8.2 mo (HR 0.44, 95% CI 0.26-0.74)

Preceding treatment

• Induction chemotherapy x 4 to 6 cycles

Chemotherapy

• Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for up to 35 cycles (2 years)

References

1. SYSUCC 2015029: Liu GY, Li WZ, Wang DS, Liang H, Lv X, Ye YF, Zhao C, Ke LR, Lv SH, Lu N, Bei WX, Cai ZC, Chen X, Liang CX, Guo X, Xia WX, Xiang YQ. Effect of Capecitabine Maintenance Therapy Plus Best Supportive Care vs Best Supportive Care Alone on Progression-Free Survival Among Patients With Newly Diagnosed Metastatic Nasopharyngeal Carcinoma Who Had Received Induction Chemotherapy: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):553-561. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02460419