Neuroblastoma is a rare cancer but is the most common malignancy of infancy.
Low-risk
Intermediate-risk, all lines of therapy
COG A3961 regimen
Regimen
To be completed.
Chemotherapy
References
- 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, induction
N5/N6
Protocol
Chemotherapy, N5 cycles
Chemotherapy, N6 cycles
References
- NB2004-HR: Berthold F, Faldum A, Ernst A, Boos J, Dilloo D, Eggert A, Fischer M, Frühwald M, Henze G, Klingebiel T, Kratz C, Kremens B, Krug B, Leuschner I, Schmidt M, Schmidt R, Schumacher-Kuckelkorn R, von Schweinitz D, Schilling FH, Theissen J, Volland R, Hero B, Simon T. Extended induction chemotherapy does not improve the outcome for high-risk neuroblastoma patients: results of the randomized open-label GPOH trial NB2004-HR. Ann Oncol. 2020 Mar;31(3):422-429. Epub 2020 Jan 24. link to original article does not contain protocol PubMed NCT03042429
High-risk, consolidation
Busulfan & Melphalan, then auto HSCT
Regimen
Note: the abstract does not specify exact days but this schedule is typical; IV dosing was used after a 2007 protocol amendment
Chemotherapy
Stem cells re-infused on day 0
References
- HR-NBL1: Ladenstein R, Pötschger U, Pearson ADJ, Brock P, Luksch R, Castel V, Yaniv I, Papadakis V, Laureys G, Malis J, Balwierz W, Ruud E, Kogner P, Schroeder H, de Lacerda AF, Beck-Popovic M, Bician P, Garami M, Trahair T, Canete A, Ambros PF, Holmes K, Gaze M, Schreier G, Garaventa A, Vassal G, Michon J, Valteau-Couanet D; SIOP Europe Neuroblastoma Group (SIOPEN). Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):500-514. Epub 2017 Mar 2. link to original article contains protocol PubMed
GM-CSF, IL-2, Isotretinoin, Dinutuximab
Regimen
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)
Chemotherapy
28-day cycle for 6 cycles
References
- 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
Regimen
Preceding treatment
- Matthay et al. 1999: HDT with purged auto HSCT versus cisplatin, doxorubicin, etoposide consolidation
Chemotherapy
28-day cycle for 6 cycles
References
- 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
- 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 & Dinutuximab
Regimen
Note: this was a second randomization and second cohort of patients enrolled in HR-NBL1.
Preceding treatment
Chemotherapy
Immunotherapy
References
- HR-NBL1: Ladenstein R, Pötschger U, Valteau-Couanet D, Luksch R, Castel V, Yaniv I, Laureys G, Brock P, Michon JM, Owens C, Trahair T, Chan GCF, Ruud E, Schroeder H, Beck Popovic M, Schreier G, Loibner H, Ambros P, Holmes K, Castellani MR, Gaze MN, Garaventa A, Pearson ADJ, Lode HN. Interleukin 2 with anti-GD2 antibody ch14 18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1617-1629. Epub 2018 Nov 12. link to original article PubMed
Relapsed or refractory
Cyclophosphamide monotherapy
Regimen
Of historic interest.
Chemotherapy
References
- 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
Regimen
Of historic interest.
Chemotherapy
References
- 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
Regimen
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
- 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 NCT01767194