Example orders for High-dose Methotrexate (MTX) & Ifosfamide in lymphoma

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

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Remember that example order sets that may contain additional information about supportive medications, suggestions for monitoring, hydration, and pre-treatment screening information for chemotherapy regimens are purely anecdotal, provided only as examples of what some other providers may be using, and are typically not based on references in the primary literature.

High-dose Methotrexate (MTX) & Ifosfamide

Original references may be found at High-dose Methotrexate (MTX) & Ifosfamide

Example regimen #1

• Methotrexate (MTX) 4000 mg/m² IV over 4 hours on day 1
  • Do not start methotrexate until urine pH is at least 8 or higher. Admix with sodium bicarbonate.
• Sodium bicarbonate 25 mEq IV once on day 1, admix with methotrexate
• Ifosfamide (Ifex) 2000 mg/m² IV over 3 hours on days 3-5
• Mesna (Mesnex) 500 mg/m² IV every 3 hours x 4 doses per day on days 3-5 with ifosfamide
  • Times for mesna in relation to start of ifosfamide; Dose 1 of mesna is at time at 0, dose 2 is 3 hours after start of ifosfamide, dose 3: 6 hours after start of ifosfamide, dose 4: 9 hours post ifosfamide.
• Folinic acid (Leucovorin) 50 mg IV every 6 hours, starting on day 2
  • To begin 24 hours after the start of day 1's methotrexate infusion and continue for at least 8 doses. Discuss changes such as potential transition to PO leucovorin with MD according to MTX levels.

Supportive medications

• Ondansetron (Zofran) 8 mg IV on days 1 to 5, 30 minutes prior to chemotherapy
• Dexamethasone (Decadron) 8 mg IV BID on days 1 to 5
• Ondansetron (Zofran) 4-8 mg IV Q8H prn nausea
• Prochlorperazine (Compazine) 10 mg PO Q6H prn nausea

Hydration:

• 150 mEq sodium bicarbonate in 1000 mL D5W, continuous at 125 mL/H, start on day 1 hours before methotrexate infusion for urine alkalinization. Continue fluids unless discussed otherwise with MD.

Monitoring:

• Check methotrexate levels 24, 48, and 72 hours after completion of methotrexate infusion.
• Check urine pH every 4 hours and notify physician if urine pH <8

Clinical scenario & comments:

• 54 year-old gentleman with stage IV diffuse large B-cell lymphoma with extranodal disease (primary testicular lymphoma), with progression after 6 cycles of R-CHOP. He only received treatment with high-dose methotrexate & ifosfamide for one cycle; treatment was complicated by acute kidney injury, with subsequent improvement back to baseline. This was followed with R-ICE therapy, with disease remission achieved and subsequent allogeneic stem cell transplant.