Extranodal NK/T-cell lymphoma, nasal type

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10 regimens on this page
10 variants on this page


Guidelines

"How I Treat"

NCCN

Untreated

Cisplatin & RT

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RT: Radiation Therapy

Regimen

Study Evidence ORR
Kim et al. 2009 Phase II 83%

Chemoradiotherapy

  • Cisplatin (Platinol) 30 mg/m2 IV once per week
  • Concurrent radiation therapy to the primary tumor, 1.8 to 2 Gy fractions (median total dose: 40 Gy), given 5 times per week.

Treatment followed 3 to 5 weeks after the last dose of cisplatin by VIPD consolidation.

References

  1. 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. 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. link to original article contains verified protocol PubMed

DEP & RT

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DEP: Dexamethasone, Etoposide, Platinol (Cisplatin)
RT: Radiation Therapy

Regimen

Study Evidence ORR
Tsai et al. 2014 Phase II 81%

Dosing details not available in the abstract.

Chemoradiotherapy

28-day cycle for 2 cycles

Patients without progression proceeded to VIPD consolidation.

References

  1. 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

DeVIC & RT

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DeVIC: Dexamethasone, VP-16 (Etoposide), Ifosfamide, Carboplatin

Regimen

Study Evidence ORR
Yamaguchi et al. 2009 (JCOG0211) Phase II 81%

Chemotherapy, Dose Level I

Chemotherapy, Dose Level II

Supportive medications

  • Filgrastim (Neupogen) (dose/route/schedule not specified) started for WBC count less than 2 x 109/L or ANC less than 1000/uL; discontinued if WBC count greater than 5 x 109/L.

21-day cycle for 3 cycles

Radiotherapy

Started simultaneously with the beginning of cycle 1 of chemotherapy

  • Stage IE disease: Concurrent radiation therapy, 2 Gy fractions x 25 fractions (total dose: 50 Gy) over 5 weeks
  • Stage IIE disease: Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions (total dose: 50.4 Gy) over 6 weeks

References

  1. 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. link to original article contains verified protocol 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, then RT

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GELOX: Gemcitabine, L-asparaginase, Oxaliplatin
RT: Radiation Therapy

Regimen

Study Evidence ORR
Wang et al. 2012 Phase II 96%

Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze).

Chemotherapy

3-weeks cycle for at least 2 cycles, followed by:

Radiotherapy

  • Involved field radiation to 56 grays (Gy) in 28 fractions, 5 fractions per week

Followed by more chemotherapy within one week of radiation completion, up to 6 total 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 contains verified protocol PubMed

LVP "Sandwich"

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LVP: L-asparaginase, Vincristine, Prednisolone

Regimen

Study Evidence ORR
Jiang et al. 2011 Phase II 84%

Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze).

Chemotherapy

21-day cycle for 2 cycles, followed by:

Radiotherapy

  • Radiation to the nasal cavity and surrounding sinuses, 56 Gy in 28 fractions, once per day, five days per week

Resume chemotherapy one week after completion of radiation, up to 6 total 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 contains verified protocol PubMed

SMILE

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SMILE: Steroid (dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide

Regimen

Study Evidence ORR
Yamaguchi et al. 2011 Phase II 79%

Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze).

Chemotherapy

Supportive medications

28-day cycle for 2 cycles

After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.

References

  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 contains verified protocol 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. 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 contains verified protocol PubMed

Consolidation after upfront therapy

VIPD

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VIPD: VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin), Dexamethasone

Regimen

Study Evidence
Kim et al. 2009 Phase II
Tsai et al. 2014 Phase II

Details here are from the Kim et al. 2009 manuscript.

Preceding treatment

Chemotherapy

Supportive medications

  • 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. 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. 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. link to original article contains verified protocol PubMed
  2. 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

Relapsed or refractory

AspaMetDex

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AspaMetDex: Asparaginase, Methotrexate, Dexamethasone

Regimen

Study Evidence ORR
Jaccard et al. 2011 Phase II 78%

Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze).

Chemotherapy

Supportive medications

21-day cycle for 3 cycles

See Jaccard et al. 2011 for details about further treatment.

References

  1. Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O; GELA and GOELAMS Intergroup. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011 Feb 10;117(6):1834-9. link to original article contains verified protocol PubMed

LVP

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LVP: L-asparaginase, Vincristine, Prednisolone

Regimen

Study Evidence ORR
Yong et al. 2003 Phase II, <20 patients 83%

Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze).

Regimen details are from a review article; original article is not available through PubMed

Chemotherapy

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. PubMed

SMILE

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SMILE: Steroid (dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide

Regimen

Study Evidence ORR
Yamaguchi et al. 2011 Phase II 79%

Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze).

Chemotherapy

Supportive medications

28-day cycle for 2 cycles

After 2 cycles, patients could receive additional treatment with SMILE and/or other chemotherapy, with or without autologous/allogeneic stem cell transplant.

References

  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 contains verified protocol 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. 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 contains verified protocol PubMed