Extranodal NK- and T-cell lymphoma, nasal type

Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.

Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.

10 regimens on this page 10 variants on this page

Untreated

Cisplatin & Concurrent RT

back to top

RT: Radiation Therapy

Regimen

Study	Evidence
Kim et al. 2009	Phase II

Chemotherapy

• 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 & Concurrent RT

back to top

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

Regimen

Study	Evidence
Tsai et al. 2014	Phase II

Dosing details not available in the abstract.

Chemotherapy

• Dexamethasone (Decadron)
• Etoposide (Vepesid)
• Cisplatin (Platinol)
• Concurrent radiation therapy to the primary tumor, 5040 cGy in 28 fractions over 5 weeks

28-day cycle x 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 & Concurrent RT

back to top

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

Regimen

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

Dose Level I

• Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 3
• Etoposide (Vepesid) 67 mg/m² IV over 2 hours once per day on days 1 to 3
• Ifosfamide (Ifex) 1000 mg/m² IV over 3 hours once per day on days 1 to 3
• Carboplatin (Paraplatin) 200 mg/m² IV over 30 minutes once on day 1

Dose Level II

• Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 3
• Etoposide (Vepesid) 100 mg/m² IV over 2 hours once per day on days 1 to 3
• Ifosfamide (Ifex) 1500 mg/m² IV over 3 hours once per day on days 1 to 3
• Carboplatin (Paraplatin) 300 mg/m² IV over 30 minutes once on day 1

Supportive medications

• Filgrastim (Neupogen) (dose/route/schedule not specified) started for leukocyte count <2,000/µL or ANC <1,000/µL; discontinued if leukocyte count >5,000/µL.

21-day cycle x 3 cycles

Concurrent radiation therapy

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

back to top

GELOX: Gemcitabine, L-asparaginase, Oxaliplatin

Regimen

Study	Evidence
Wang et al. 2012	Phase II

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

• 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 once on day 1

3-weeks cycle for at least 2 cycles, then:

• 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"

back to top

LVP: L-asparaginase, Vincristine, Prednisolone

Regimen

Study	Evidence
Jiang et al. 2011	Phase II

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

• 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
• Prednisolone (Millipred) 100 mg PO once per day on days to 5

3-week cycle x 2 cycles, then

• 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

back to top

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

Regimen

Study	Evidence
Yamaguchi et al. 2011	Phase II

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

• Dexamethasone (Decadron) 40 mg PO/IV once per day on days 2 to 4
• 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 medications

• Folinic acid (Leucovorin) 15 mg PO/IV Q6H x 4 doses per day on days 2 to 4, beginning 30 hours after completion of Methotrexate (MTX)
• 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 (Ifex), and third dose given 8 hours after start of Ifosfamide (Ifex)
• Filgrastim (Neupogen) (dose not specified) SC/IV once per day starting on day 6, given until WBC >5 x 10⁹/L
• Trimethoprim/Sulfamethoxazole (Bactrim DS) prophylaxis recommended

28-day cycle x 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

back to top

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

Regimen

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

Treatment in Kim et al. 2009 preceded by cisplatin & concurrent RT. Treatment in Tsai et al. 2014 preceded by DEP & concurrent RT. Details here are from the Kim et al. 2009 manuscript:

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 1 hour once per day on days 1 to 3
• Cisplatin (Platinol) 33 mg/m² IV over 1 hour once per day on days 1 to 3
• Dexamethasone (Decadron) 40 mg PO/IV once per day on days 1 to 4

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 x 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/refractory

AspaMetDex

back to top

AspaMetDex: Asparaginase, Methotrexate, Dexamethasone

Regimen

Study	Evidence
Jaccard et al. 2011	Phase II

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

• Asparaginase (Elspar) 6000 units/m² IM once per day on days 2, 4, 6, 8
  • Patients who had allergies to Asparaginase (Elspar) received Asparaginase Erwinia chrysanthemi (Erwinaze) 20,000 units/m² IM once per day on days 2, 4, 6, 8
• Methotrexate (MTX) 3000 mg/m² (route not specified) once on day 1
  • Patients >70 years old received Methotrexate (MTX) 2000 mg/m² (route not specified) once on day 1
• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
  • Patients >70 years old received Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4

Supportive medications

• Trimethoprim/Sulfamethoxazole (Bactrim DS) (dose/route/schedule not specified) prophylaxis, discontinued during Methotrexate (MTX) administration
• Valacyclovir (Valtrex) (dose/route/schedule not specified) prophylaxis
• For Methotrexate (MTX): alkaline hydration and Folinic acid (Leucovorin) rescue (dose/route/schedule not specified)

21-day cycle x 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

back to top

LVP: L-asparaginase, Vincristine, Prednisolone

Regimen

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

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

• 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
• Prednisolone (Millipred) 100 mg PO once per day on days to 5

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

back to top

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

Regimen

Study	Evidence
Yamaguchi et al. 2011	Phase II

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

• Dexamethasone (Decadron) 40 mg PO/IV once per day on days 2 to 4
• 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 medications

• Folinic acid (Leucovorin) 15 mg PO/IV Q6H x 4 doses per day on days 2 to 4, beginning 30 hours after completion of Methotrexate (MTX)
• 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 (Ifex), and third dose given 8 hours after start of Ifosfamide (Ifex)
• Filgrastim (Neupogen) (dose not specified) SC/IV once per day starting on day 6, given until WBC >5 x 10⁹/L
• Trimethoprim/Sulfamethoxazole (Bactrim DS) prophylaxis recommended

28-day cycle x 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