SMILE

Indication

Advanced-stage NK-cell lymphomas

Regimen

Methotrexate with leucovorin 2 g/m2 IV over 6 h d1
Ifosfamide with mesna	1.5 g/m2 IV d2, 3 and 4
Dexamethasone 40 mg IV or oral	d2, 3 and 4
Etoposide	100 mg/m2 IV d2, 3 and 4
L-asparaginase (Leunase) 6000 U/m2 IV d8, 10, 12, 14, 16, 18 and 20
G-CSF r to be started on day 6. Cycles to be repeated every 28 days.

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 greater than or equal to 3 liters per day on days 1 to 4
• Filgrastim (Neupogen) 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
• 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

Motoko Yamaguchi Ritsuro Suzuki, Yok-Lam Kwong3 et al .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

Yamaguchi M et al. 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. JCO November 20, 2011 vol. 29 no. 33 4410-4416

M. Yamaguchi, Y. Kwong, Y. Maeda, C. Hashimoto, W. Kim et al Phase II study of SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-cell lymphoma, nasal type: NKTSG study

Medscape. Diagnosis and Management of Natural Killer-cell Malignancies: Treatment of Advanced-stage NK-cell Lymphoma (Nasal & Non-nasal)