NK- and T-cell lymphoma

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5 regimens on this page 5 variants on this page

Guidelines

NCCN

• NCCN Guidelines - T-cell Lymphomas

All lines of therapy

DDGP

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DDGP: Dexamethasone, DDP (Cisplatin), Gemcitabine, Pegaspargase

Regimen

Study	Evidence	Comparator	Efficacy
Li et al. 2016	Phase III	SMILE	Seems to have superior OS

Note: drug names but no further details were provided in the abstract; dosing information is from the NCT record.

Chemotherapy

• Dexamethasone (Decadron) 15 mg/m² IV once per day on days 1 to 5
• Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 4
• Gemcitabine (Gemzar) 800 mg/m² IV over 30 minutes once per day on days 1 & 8
• Pegaspargase (Oncaspar) 2500 IU/m² IM once on day 1

21-day cycle for at least 3 cycles

References

1. Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. link to original article PubMed

SMILE

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

Regimen

Study	Evidence	Comparator	Efficacy
Kwong et al. 2012	Phase II
Li et al. 2016	Phase III	DDGP	Seems to have inferior OS

Note: 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 once per day on days 2 to 4
• Methotrexate (MTX) 2000 mg/m² in 500 mL normal saline IV over 6 hours once on day 1
• Ifosfamide (Ifex) 1500 mg/m² in 1 liter normal saline IV over 6 hours once per day on days 2 to 4, given together with Mesna (Mesnex)
• Asparaginase (Elspar) 6000 units/m² in 250 mL normal saline IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
  • Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi (Erwinaze) used for patients who developed sensitivity to L-asparaginase from E. coli
• Etoposide (Vepesid) 100 mg/m² in 500 mL normal saline IV over 2 hours once per day on days 2 to 4

Supportive medications

• Folinic acid (Leucovorin) 45 mg PO Q6H x 4 doses per day on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of Methotrexate (MTX)
  • Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
• Mesna (Mesnex) 900 mg/m² IV over 6 hours once per day on days 2 to 4, given together with Ifosfamide (Ifex)
• Hydration with normal saline (no volume specified) Q8H x 1 day prior to Methotrexate (MTX)
• Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of >=3 liters per day on days 1 to 4
• Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6, given until ANC >1 x 10⁹/L
• Cotrimoxazole or Pentamidine (Nebupent) for PJP prophylaxis
• Famotidine (Pepcid) and potassium slow release tablets (no dose specified) "for Dexamethasone (Decadron)" on days 2 to 4
• Chlorpheniramine (Chlor-Trimeton) 10 mg PO once prior to Asparaginase (Elspar) infusions on days 8, 10, 12, 14, 16, 18, 20
• Hydrocortisone (Cortef) 100 mg IV once prior to Asparaginase (Elspar) infusions on days 8, 10, 12, 14, 16, 18, 20

Given for up to 6 cycles

Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.

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. Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. link to original article supplemental materials supplemental materials contain verified protocol PubMed
3. Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in Newly Diagnosed Advanced Natural Killer/T-Cell Lymphoma: A Randomized Controlled, Multicenter, Open-label Study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. link to original article PubMed