Extranodal NK- and T-cell lymphoma, nasal type

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Bhagirathbhai Dholaria, MBBS
Vanderbilt University
Nashville, TN, USA
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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


NCCN


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

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

  1. 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 PubMed 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

Chemotherapy

Radiotherapy

28-day cycle for 2 cycles

Subsequent treatment

References

  1. 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 PubMed 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

Chemotherapy

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

  1. 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 PubMed
    1. 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 PubMed


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

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

21-day cycle for up to 4 cycles

References

  1. 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 PubMed


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

Glucocorticoid therapy

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

Glucocorticoid therapy

21-day cycle for up to 4 cycles

References

  1. 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 PubMed 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

Glucocorticoid therapy

21-day cycle for at least 3 cycles, followed by:


Definitive therapy

Radiotherapy

One course, followed by:


Consolidation

Chemotherapy

Glucocorticoid therapy

21-day cycle for a maximum of 7 cycles

References

  1. 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 PubMed


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

Chemotherapy

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

  1. 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 PubMed content property of HemOnc.org
  2. 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 PubMed 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

Chemotherapy

Glucocorticoid therapy

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

  1. 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 PubMed NCT00418535
  2. 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 PubMed 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

Glucocorticoid therapy

21- to 28-day cycle for up to 6 cycles

References

  1. 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 PubMed


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

Chemotherapy

Supportive therapy

28-day cycle for 2 cycles (see note)

References

  1. 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 PubMed


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