Neuroblastoma

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Wayne H. Liang, MD, MS
UAB
Birmingham, AL

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

6 regimens on this page
6 variants on this page


Low-risk

Intermediate-risk, all lines of therapy

COG A3961 regimen

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Regimen

Study Evidence
Baker et al. 2010 (COG A3961) Non-randomized

To be completed.

Chemotherapy

  • See paper for details

References

  1. COG A3961: Baker DL, Schmidt ML, Cohn SL, Maris JM, London WB, Buxton A, Stram D, Castleberry RP, Shimada H, Sandler A, Shamberger RC, Look AT, Reynolds CP, Seeger RC, Matthay KK; Children’s Oncology Group. Outcome after reduced chemotherapy for intermediate-risk neuroblastoma. N Engl J Med. 2010 Sep 30;363(14):1313-23. link to original article link to PMC article PubMed

High-risk, consolidation

Dinutuximab, GM-CSF, IL-2, Isotretinoin

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Regimen

Study Evidence Comparator Comparative Efficacy
Yu et al. 2010 (COG ANBL0032) Phase III (E) 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: 3,000,000 IU/m2/day IV continuous infusion over 96 hours, started on day 0, then 4,500,000 IU/m2/day IV continuous infusion over 96 hours, started on day 7 (total dose per cycle: 30,000,000 IU/m2)
  • Isotretinoin (Accutane) 160 mg/m2/day PO on days 14 to 27

28-day cycle for 6 cycles

References

  1. COG ANBL0032: 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 Comparative Efficacy
Matthay et al. 1999 Phase III (E) No further therapy Seems to have superior EFS
Yu et al. 2010 (COG ANBL0032) Phase III (C) Dinutuximab, GM-CSF, IL-2, Isotretinoin Seems to have inferior OS

Preceding treatment

  • Matthay et al. 1999: HDT with purged auto HSCT versus cisplatin, doxorubicin, etoposide consolidation

Chemotherapy

28-day cycle for 6 cycles

References

  1. Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, Swift P, Shimada H, Black CT, Brodeur GM, Gerbing RB, Reynolds CP; Children's Cancer Group. Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. N Engl J Med. 1999 Oct 14;341(16):1165-73. link to original article contains verified protocol PubMed
  2. COG ANBL0032: 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

Cyclophosphamide monotherapy

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Regimen

Study Evidence
Thurman et al. 1964 Non-randomized

Of historic interest.

Chemotherapy

References

  1. Thurman WG, Fernbach DJ, Sullivan MP. Cyclophosphamide therapy in childhood neuroblastoma. N Engl J Med. 1964 Jun 18;270:1336-40. link to original article PubMed

Cyclophosphamide & Vincristine

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Regimen

Study Evidence
Evans et al. 1969 Non-randomized

Of historic interest.

Chemotherapy

References

  1. Evans AE, Heyn RM, Newton WA Jr, Leikin SL. Vincristine sulfate and cyclophosphamide for children with metastatic neuroblastoma. JAMA. 1969 Feb 17;207(7):1325-7. link to original article PubMed

Irinotecan, Temozolomide, Dinutuximab

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Regimen

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

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

Chemotherapy

Immunotherapy

  • 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

21-day cycle for up to 17 cycles

References

  1. COG ANBL1221: 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