Neuroblastoma

Section editor
	Wayne H. Liang, MD, MS Birmingham, AL LinkedIn Twitter: WayneLiangMD

Neuroblastoma is a rare cancer but is the most common malignancy of infancy.

14 regimens on this page 15 variants on this page

High-risk, consolidation

Dinutuximab, GM-CSF, IL-2, Isotretinoin

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Regimen

Study	Evidence	Comparator	Efficacy
Yu et al. 2010 (COG ANBL0032)	Phase III	Isotretinoin	Seems to have superior OS

Note: in distinction from most chemotherapy regimens, the first day of a cycle is day 0 and the last day of a 28-day cycle is day 27.

Immunotherapy

• Dinutuximab (Unituxin) as follows:
  • Cycles 1, 3, 5: 25 mg/m² IV once per day on days 3 to 6
  • Cycles 2 & 4: 25 mg/m² IV once per day on days 7 to 10
• Sargramostim (Leukine) as follows:
  • Cycles 1, 3, 5: 250 mcg/m² SC once per day on days 0 to 13
• Aldesleukin (Proleukin) as follows:
  • Cycles 2 & 4: 3.0 x 10⁶ IU/m²/day IV continuous infusion on days 0 to 3, then 4.5 x 10⁶ IU/m²/day IV continuous infusion on days 7 to 10
• Isotretinoin (Accutane) 160 mg/m²/day PO on days 14 to 27

28-day cycle for 6 cycles

References

1. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. link to original article link to PMC article contains verified protocol PubMed

Isotretinoin monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Yu et al. 2010 (COG ANBL0032)	Phase III	Dinutuximab, GM-CSF, IL-2, Isotretinoin	Seems to have inferior OS

Chemotherapy

• Isotretinoin (Accutane) 80 mg/m² BID on days 1 to 14

28-day cycle for 6 cycles

References

1. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, Shimada H, Grupp SA, Seeger R, Reynolds CP, Buxton A, Reisfeld RA, Gillies SD, Cohn SL, Maris JM, Sondel PM; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1324-34. link to original article link to PMC article contains verified protocol PubMed

Relapsed or refractory

Irinotecan, Temozolomide, Dinutuximab

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Regimen

Study	Evidence	Comparator	Efficacy
Mody et al. 2017 (COG ANBL1221)	Randomized phase II, <20 pts	Irinotecan, Temozolomide, Temsirolimus	Superior ORR

Note: this dinutuximab dose is based on a mid-protocol revision.

Chemoimmunotherapy

• Irinotecan (Camptosar) 50 mg/m² IV over 90 minutes once per day on days 1 to 5
• Temozolomide (Temodar) 100 mg/m² PO once per day on days 1 to 5
• Dinutuximab (Unituxin) 17.5 mg/m² IV over 10 hours once per day on days 2 to 5
  • Infusion time could be extended to 20 hours "if patients experienced pain, fever, tachycardia, tachypnea, or hypotension unresponsive to supportive measures."

Supportive medications

• Sargramostim (Leukine) 250 mcg/m² SC once per day on days 6 to 12

21-day cycle for up to 17 cycles

References

1. Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Sondel PM, Bender JG, Maris JM, Park JR, Bagatell R. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):946-957. Epub 2017 May 23. link to original article link to PMC article contains verified protocol PubMed