Extranodal NK- and T-cell lymphoma, nasal type

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Most of these regimens are specific to the nasal type of ENKTCL. For more generic NKTCL regimens, please see this page.
Last updated on 2024-07-23:10 regimens on this page
10 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESMO==
*2015: d'Amore et al. Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - T-cell Lymphomas.
=Untreated=
==Cisplatin & RT==
Cisplatin & RT: Cisplatin & Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Kim et al. 2009 (CISL 2004-10-08)	2006-04 to 2007-10 	Phase 2 	ORR: 83%
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22
====Radiotherapy====
*Concurrent radiation therapy to the primary tumor, 1.8 to 200 cGy fractions (median total dose: 4000 cGy), given 5 times per week.
4-week course
====Subsequent treatment====
*VIPD consolidation, 3 to 5 weeks after the last dose of cisplatin
===References===
#CISL 2004-10-08: Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS; Consortium for Improving Survival of Lymphoma. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009 Dec 10;27(35):6027-32. Epub 2009 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00418535
==DEP & RT==
DEP & RT: Dexamethasone, Etoposide, Platinol (Cisplatin), Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Tsai et al. 2014 (T1405)	2006-05 to 2009-09 	Phase 2 	ORR: 81%
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg/m2/day IV on days 1 to 3
====Chemotherapy====
*Etoposide (Vepesid) 75 mg/m2 IV over 60 minutes once per day on days 1 to 3
*Cisplatin (Platinol) 75 mg/m2 IV over 4 hours once on day 1
====Radiotherapy====
*Concurrent radiation therapy to the primary tumor: 5040 cGy in 28 fractions
28-day cycle for 2 cycles
====Subsequent treatment====
*VIPD consolidation
===References===
#T1405: Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015 Feb;94(2):130-7. Epub 2014 Oct 10. link to original article dosing details on CT.gov have been reviewed by our editors EuroPMC NCT00292695
==DeVIC & RT==
DeVIC & RT: Dexamethasone, VP-16 (Etoposide), Ifosfamide, Carboplatin, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Yamaguchi et al. 2009 (JCOG0211)	2003-09 to 2006-12 	Phase 1/2	ORR: 81%
Note: this is the recommended dose level used in the phase 2 portion.
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 3
====Chemotherapy====
*Etoposide (Vepesid) 67 mg/m2 IV over 2 hours once per day on days 1 to 3, 22 to 24, 43 to 45
*Ifosfamide (Ifex) 1000 mg/m2 IV over 3 hours once per day on days 1 to 3, 22 to 24, 43 to 45
*Carboplatin (Paraplatin) 200 mg/m2 IV over 30 minutes once per day on days 1, 22, 43
====Supportive therapy====
*Filgrastim (Neupogen) (dose/route/schedule not specified) started for WBC count less than 2 x 109/L or ANC less than 1000/μL; discontinued if WBC count more than 5 x 109/L
====Radiotherapy====
Started simultaneously with the beginning of cycle 1 of chemotherapy
*Concurrent radiation therapy by the following stage-based criteria:
**Stage IE: 200 cGy fractions x 25 fractions (total dose: 5000 cGy)
**Stage IIE: 180 cGy fractions x 28 fractions (total dose: 5040 cGy)
9-week course
===References===
# JCOG0211: Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Ohshima K, Matsuno Y, Terauchi T, Nawano S, Ishikura S, Kagami Y, Hotta T, Oshimi K. Phase I/II study of concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: Japan Clinical Oncology Group Study JCOG0211. J Clin Oncol. 2009 Nov 20;27(33):5594-600. Epub 2009 Oct 5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## Update: Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Hotta T, Tsukasaki K, Oshimi K. Concurrent chemoradiotherapy for localized nasal natural killer/T-cell lymphoma: an updated analysis of the Japan clinical oncology group study JCOG0211. J Clin Oncol. 2012 Nov 10;30(32):4044-6. Epub 2012 Oct 8. link to original article EuroPMC
==GELOX/RT==
GELOX/RT: Gemcitabine, L-asparaginase, Oxaliplatin, alternating with Radiation Therapy
Study 	Dates of enrollment	Evidence	Efficacy
Wang et al. 2012	2008-01 to 2011-07 	Phase 2 	ORR: 96%
Note: total number of chemotherapy cycles was limited to 6.
===Induction===
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*Asparaginase (Elspar) 6000 units/m2 IV once per day on days 1 to 7
*Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for at least 2 cycles, followed by:
===Definitive therapy===
====Radiotherapy====
*IFRT to 5600 cGy in 28 fractions, 5 fractions per week
5.5-week course, followed within one week by:
===Consolidation===
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*Asparaginase (Elspar) 6000 units/m2 IV once per day on days 1 to 7
*Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for up to 4 cycles
===References===
# Wang L, Wang ZH, Chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX) followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/T-cell lymphoma. Cancer. 2013 Jan 15;119(2):348-55. Epub 2012 Jul 18. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==LVP Sandwich==
LVP: L-asparaginase, Vincristine, Prednisolone
Study 	Dates of enrollment	Evidence	Efficacy
Jiang et al. 2011	2008-07 to 2009-11 	Phase 2 	ORR: 84%
===Induction===
====Chemotherapy====
*Asparaginase (Elspar) 6000 units/m2 IV once per day on days 1 to 5
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 2 cycles, followed by:
===Definitive therapy===
====Radiotherapy====
*External beam radiotherapy to the nasal cavity and surrounding sinuses, 5600 cGy in 28 fractions, once per day, five days per week
5.5-week course, followed in one week by:
===Consolidation===
====Chemotherapy====
*Asparaginase (Elspar) 6000 units/m2 IV once per day on days 1 to 5
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for up to 4 cycles
===References===
# Jiang M, Zhang H, Jiang Y, Yang Q, Xie L, Liu W, Zhang W, Ji X, Li P, Chen N, Zhao S, Wang F, Zou L. Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma. Cancer. 2012 Jul 1;118(13):3294-301. Epub 2011 Dec 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ChicTR-TNC-00000394
==MESA/RT==
MESA/RT: Methotrexate, Etoposide, Steroid (dexamethasone), PEG-A-sparaginase alternating with Radiation Ttherapy
Study 	Dates of enrollment	Evidence	Efficacy
Liang et al. 2016 (MESA-NKT2013)	2012-12 to 2015-01 	Phase 2 	ORR: 87%
===Induction===
====Chemotherapy====
*Methotrexate (MTX) 2000 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 2 to 4
*Pegaspargase (Oncaspar) 2500 IU/m2 IM once on day 5
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg/m2 IV once per day on days 2 to 5
21-day cycle for at least 3 cycles, followed by:
===Definitive therapy===
====Radiotherapy====
*Radiation therapy, 45 to 5000 cGy in 25 fractions
One course, followed by:
===Consolidation===
====Chemotherapy====
*Methotrexate (MTX) 2000 mg/m2 IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 2 to 4
*Pegaspargase (Oncaspar) 2500 IU/m2 IM once on day 5
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 20 mg/m2 IV once per day on days 2 to 5
21-day cycle for a maximum of 7 cycles
===References===
# MESA-NKT2013: Liang R, Gao GX, Chen JP, Wang JS, Wang XM, Zeng Y, Bai QX, Zhang T, Yang L, Dong BX, Gu HT, Shu MM, Hao CX, Wang JH, Zhang N, Chen XQ. A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China. Hematol Oncol. 2017 Dec;35(4):619-629. Epub 2016 Oct 10. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==SMILE==
SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Yamaguchi et al. 2011	2007-07 to 2009-10 	Phase 2 	ORR: 79%
Note: After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg IV or PO once per day on days 2 to 4
====Chemotherapy====
*Methotrexate (MTX) 2000 mg/m2 IV over 6 hours once on day 1
*Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 2 to 4
*Asparaginase (Elspar) 6000 units/m2 IV once per day on days 8, 10, 12, 14, 16, 18, 20
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 2 to 4
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg IV or PO every 6 hours on days 2 to 4, beginning 30 hours after completion of methotrexate
*Mesna (Mesnex) 300 mg/m2 IV three times per day on days 2 to 4; first dose given together with ifosfamide, second dose given at 4 hours after start of ifosfamide, and third dose given 8 hours after start of ifosfamide
*Filgrastim (Neupogen) (dose not specified) IV or SC once per day, starting on day 6, continued until WBC count more than 5 x 109/L
*Trimethoprim-Sulfamethoxazole (Bactrim DS) prophylaxis recommended
28-day cycle for 2 cycles (see note)
===References===
# Phase 1: Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC content property of HemOnc.org
# Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R; NK-Cell Tumor Study Group. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011 Nov 20;29(33):4410-6. Epub 2011 Oct 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000000712
=Consolidation after upfront therapy=
==VIPD==
VIPD: VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin), Dexamethasone
===Regimen===
Study 	Dates of enrollment	Evidence
Kim et al. 2009 (CISL 2004-10-08)	2006-04 to 2007-10 	Phase 2
Tsai et al. 2014 (T1405) 	2006-05 to 2009-09 	Phase 2
Details here are from CISL 2004-10-08.
====Preceding treatment====
*CISL 2004-10-08: Cisplatin & RT induction
*T1405: DEP & RT induction
====Chemotherapy====
*Etoposide (Vepesid) 100 mg/m2 IV over 90 minutes once per day on days 1 to 3
*Ifosfamide (Ifex) 1200 mg/m2 IV over 60 minutes once per day on days 1 to 3
*Cisplatin (Platinol) 33 mg/m2 IV over 60 minutes once per day on days 1 to 3
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
====Supportive therapy====
*Mesna (Mesnex) 240 mg/m2 IV over 15 minutes once per day on days 1 to 3
*G-CSF given for grade 3 or 4 neutropenia
21-day cycle for up to 3 cycles
===References===
# CISL 2004-10-08: Kim SJ, Kim K, Kim BS, Kim CY, Suh C, Huh J, Lee SW, Kim JS, Cho J, Lee GW, Kang KM, Eom HS, Pyo HR, Ahn YC, Ko YH, Kim WS; Consortium for Improving Survival of Lymphoma. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: Consortium for Improving Survival of Lymphoma study. J Clin Oncol. 2009 Dec 10;27(35):6027-32. Epub 2009 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00418535
#T1405: Tsai HJ, Lin SF, Chen CC, Chen TY, Su WC, Hwang WL, Lin JC, Chiou TJ, Kao WY, Chiu CF, Chang YF, Chang JS, Chang MC, Su IJ. Long-term results of a phase II trial with frontline concurrent chemoradiotherapy followed by consolidation chemotherapy for localized nasal natural killer/T-cell lymphoma. Eur J Haematol. 2015 Feb;94(2):130-7. Epub 2014 Oct 10. link to original article EuroPMC NCT00292695
=Relapsed or refractory=
==L-Asparaginase, Vincristine, Dexamethasone==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Yong et al. 2003	1992-03 to 2002-03 	Phase 2, fewer than 20 patients	ORR: 83%
====Chemotherapy====
*Asparaginase (Elspar) 6000 units/m2 IV over 30 minutes once per day on days 1 to 7
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 10 mg IV once per day on days 1 to 7
21- to 28-day cycle for up to 6 cycles
===References===
# Yong W, Zheng W, Zhang Y, Zhu J, Wei Y, Zhu D, Li J. L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol. 2003 Aug;78(2):163-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==SMILE==
SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide
===Regimen===
Study 	Dates of enrollment	Evidence	Efficacy
Yamaguchi et al. 2011	2007-07 to 2009-10 	Phase 2 	ORR: 79%
Note: After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg IV or PO once per day on days 2 to 4
====Chemotherapy====
*Methotrexate (MTX) 2000 mg/m2 IV over 6 hours once on day 1
*Ifosfamide (Ifex) 1500 mg/m2 IV once per day on days 2 to 4
*Asparaginase (Elspar) 6000 units/m2 IV once per day on days 8, 10, 12, 14, 16, 18, 20
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 2 to 4
====Supportive therapy====
*Leucovorin (Folinic acid) 15 mg IV or PO every 6 hours on days 2 to 4, beginning 30 hours after completion of methotrexate
*Mesna (Mesnex) 300 mg/m2 IV three times per day on days 2 to 4; first dose given together with Ifosfamide (Ifex), second dose given at 4 hours after start of ifosfamide, and third dose given 8 hours after start of ifosfamide
*Filgrastim (Neupogen) (dose not specified) IV or SC once per day, starting on day 6, given until WBC count more than 5 x 109/L
*Trimethoprim-Sulfamethoxazole (Bactrim DS) prophylaxis recommended
28-day cycle for 2 cycles (see note)
===References===
# Yamaguchi M, Kwong YL, Kim WS, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R; NK-Cell Tumor Study Group. Phase II study of SMILE chemotherapy for newly diagnosed stage IV, relapsed, or refractory extranodal natural killer (NK)/T-cell lymphoma, nasal type: the NK-Cell Tumor Study Group study. J Clin Oncol. 2011 Nov 20;29(33):4410-6. Epub 2011 Oct 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
Category:Extranodal NK- and T-cell lymphoma, nasal type regimens
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