Neuroblastoma
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Neuroblastoma |
14 regimens on this page
15 variants on this page
|
ICD-O-3 code: 123.456 |
Neuroblastoma is a rare cancer but is the most common malignancy of infancy.
High Risk
COG ANBL0931
COG ANBL0532 Regimen B
Induction,
Chemotherapy, Cycle 1 (CPM + TOPO)
- Cyclophosphamide (Cytoxan) by the following weight-based criteria:
- ≤ 12 kg: 13.3 mg/kg iV over 30 to 60 minutes once daily on days 1 through 5
- > 12 kg: 400 mg/m2 IV over 30 to 60 minutes once daily on days 1 through 5
- Topotecan (Hycamtin) 1.2 mg/m2 IV over 30 minutes once daily on days 1 through 5
21 Day Cycle
Chemotherapy, Cycle 2 (CPM + TOPO)
- Cyclophosphamide (Cytoxan) by the following weight-based criteria:
- ≤ 12 kg: 13.3 mg/kg iV over 30 to 60 minutes once daily on days 1 through 5
- > 12 kg: 400 mg/m2 IV over 30 to 60 minutes once daily on days 1 through 5
- Topotecan (Hycamtin) 1.2 mg/m2 IV over 30 minutes once daily on days 1 through 5
21 Day Cycle
Supportive Therapy, Cycle 2
- Filgrastim (Neupogen) 5 μg/kg SubQ or IV once daily on Day 6 beginning 24 hours after completion of chemotherapy and continuing until ANC > 1000/μL
- Filgrastim (Neupogen) 10 μg/kg SubQ or IV once daily beginning once ANC > 1000/μL and continuing until PBSC harvest is complete
- PBSC harvest on day 14
21 Day Cycle
Chemotherapy, Cycle 3 (CDDP + ETOP)
- Cisplatin (Platinol) by the following weight-based criteria:
- ≤ 12 kg: 1.66 mg/kg IV over 1 hour once daily on days 1 through 4
- > 12 kg: 50 mg/m2 IV over 1 hour once daily on days 1 through 4
- Etoposide (Vepesid) by the following weight-based criteria:
- ≤ 12 kg: 6.67 mg/kg IV over 1 hour once daily on days 1 through 3
- > 12 kg: 200 mg/m2 IV over 1 hour once daily on days 1 through 3
Chemotherapy, Cycle 4 (CPM + DOXO + VCR)
- Cyclophosphamide (Cytoxan) by the following weight-based criteria:
- ≤ 12 kg: 70 mg/kg iV over 6 hours once daily on days 1 through 2
- > 12 kg: 2100 mg/m2 IV over 6 hours once daily on days 1 through 2
- Vincristine (Oncovin) by the following criteria:
- < 12 months: 0.017 mg/kg (Max Dose of 2 mg in 72 hours) IV over 1 minute or infusion (per institutional policy) once daily before Doxorubicin (Adriamycin) on days 1 through 3
- ≥ 12 months and > 12 kg: 0.097 mg/m2 or 0.022 mg/kg (choose lower dose) (Max Dose of 2 mg in 72 hours) IV over 1 minute or infusion (per institutional policy) once daily before Doxorubicin (Adriamycin) on days 1 through 3
- ≥ 12 months and ≤ 12 kg: 0.022 mg/kg (Max Dose of 2 mg in 72 hours) IV over 1 minute or infusion (per institutional policy) once daily before Doxorubicin (Adriamycin) on days 1 through 3
- Doxorubicin (Adriamycin) by the following weight-based criteria:
- ≤ 12 kg: 0.83 mg/kg iV over 24 hours once daily on days 1 through 3
- > 12 kg: 25 mg/m2 IV over 24 hours once daily on days 1 through 3
21 Day Cycle
Supportive Therapy, Cycle 4 (CPM + DOXO + VCR)
- Mesna (Mesnex) by the following weight-based criteria:
- ≤ 12 kg: 14 mg/kg IV over 15 minutes immediately prior to each Cyclophosphamide (Cytoxan) dose and again at 4 and 8 hours after eachCyclophosphamide (Cytoxan) infusion
- > 12 kg: 420 mg/m2 IV over 15 minutes immediately prior to each Cyclophosphamide (Cytoxan) dose and again at 4 and 8 hours after eachCyclophosphamide (Cytoxan) infusion
21 Day Cycle
Chemotherapy, Cycle 5 (CDDP + ETOP)
- Cisplatin (Platinol) by the following weight-based criteria:
- ≤ 12 kg: 1.66 mg/kg IV over 1 hour once daily on days 1 through 4
- > 12 kg: 50 mg/m2 IV over 1 hour once daily on days 1 through 4
- Etoposide (Vepesid) by the following weight-based criteria:
- ≤ 12 kg: 6.67 mg/kg IV over 1 hour once daily on days 1 through 3
- > 12 kg: 200 mg/m2 IV over 1 hour once daily on days 1 through 3
21 Day Cycle
Chemotherapy, Cycle 6 (CPM + DOXO + VCR)
- Cyclophosphamide (Cytoxan) by the following weight-based criteria:
- ≤ 12 kg: 70 mg/kg iV over 6 hours once daily on days 1 through 2
- > 12 kg: 2100 mg/m2 IV over 6 hours once daily on days 1 through 2
- Vincristine (Oncovin) by the following criteria:
- < 12 months: 0.017 mg/kg (Max Dose of 2 mg in 72 hours) IV over 1 minute or infusion (per institutional policy) once daily before Doxorubicin (Adriamycin) on days 1 through 3
- ≥ 12 months and > 12 kg: 0.097 mg/m2 or 0.022 mg/kg (choose lower dose) (Max Dose of 2 mg in 72 hours) IV over 1 minute or infusion (per institutional policy) once daily before Doxorubicin (Adriamycin) on days 1 through 3
- ≥ 12 months and ≤ 12 kg: 0.022 mg/kg (Max Dose of 2 mg in 72 hours) IV over 1 minute or infusion (per institutional policy) once daily before Doxorubicin (Adriamycin) on days 1 through 3
- Doxorubicin (Adriamycin) by the following weight-based criteria:
- ≤ 12 kg: 0.83 mg/kg iV over 24 hours once daily on days 1 through 3
- > 12 kg: 25 mg/m2 IV over 24 hours once daily on days 1 through 3
21 Day Cycle
Supportive Therapy, Cycle 6 (CPM + DOXO + VCR)
- Mesna (Mesnex) by the following weight-based criteria:
- ≤ 12 kg: 14 mg/kg IV over 15 minutes immediately prior to each Cyclophosphamide (Cytoxan) dose and again at 4 and 8 hours after eachCyclophosphamide (Cytoxan) infusion
- > 12 kg: 420 mg/m2 IV over 15 minutes immediately prior to each Cyclophosphamide (Cytoxan) dose and again at 4 and 8 hours after eachCyclophosphamide (Cytoxan) infusion
21 Day Cycle
Consolidation,
Chemotherapy, Tandem HSCT #1 (Thiotepa and Cyclophosphamide)
- Thiotepa (Thioplex) by the following weight-based criteria:
- ≤ 12 kg: 10 mg/kg IV over 2 hours once daily on days -7, -6, -5
- > 12 kg: 300 mg/m2 IV over 2 hours once daily on days -7, -6, -5
- Cyclophosphamide (Cytoxan) by the following weight-based criteria:
- ≤ 12 kg: 50mg/kg IV over 1 hour once daily on days -5, -4, -3, -2
- > 12 kg: 1500 mg/m2 IV over 1 hour once daily on days -5, -4, -3, -2
- PBSC on day 0
50 Day Cycle
Supportive therapy, Tandem HSCT #1 (Thiotepa and Cyclophosphamide)
- Mesna (Mesnex) by the following weight-based criteria:
- ≤ 12 kg: 10 mg/kg IV over 15 minutes immediately prior to each Cyclophosphamide (Cytoxan) dose and again at 4 and 8 hours after eachCyclophosphamide (Cytoxan) infusion
- > 12 kg: 300 mg/m2 IV over 15 minutes immediately prior to each Cyclophosphamide (Cytoxan) dose and again at 4 and 8 hours after eachCyclophosphamide (Cytoxan) infusion
- Filgrastim (Neupogen) 5 μg/kg SubQ or IV once daily starting on day 0 and continuing until post-nadir ANC > 2000/μL for 3 consecutive days
50 Day Cycle
Chemotherapy, Tandem HSCT #2 (CEM)
- Melphalan (Alkeran) by the following criteria:
- ≤ 12 kg and GFR ≥ 100 mL/min: 2 mg/kg IV over 15 to 30 minutes once daily on days -7, -6, -5
- > 12 kg and GFR ≥ 100 mL/min: 60 mg/m2 IV over 15 to 30 minutes once daily on days -7, -6, -5
- ≤ 12 kg and GFR between 100 mL/min and 60 mL/min: 2 mg/kg IV over 15 to 30 minutes once daily on days -7, -6, -5
- > 12 kg and GFR between 100 mL/min and 60 mL/min: 60 mg/m2 IV over 15 to 30 minutes once daily on days -7, -6, -5
- Etoposide (Vepesid) by the following criteria:
- ≤ 12 kg and GFR ≥ 100 mL/min: 12 mg/kg IV over 24 hours once daily on days -7, -6, -5, -4
- > 12 kg and GFR ≥ 100 mL/min: 300 mg/m2 IV over 24 hours once daily on days -7, -6, -5, -4
- ≤ 12 kg and GFR between 100 mL/min and 60 mL/min: 6.7 mg/kg IV over 24 hours once daily on days -7, -6, -5, -4
- > 12 kg and GFR between 100 mL/min and 60 mL/min: 200 mg/m2 IV over 24 hours once daily on days -7, -6, -5, -4
- Carboplatin (Paraplatin) by the following criteria:
- ≤ 12 kg and GFR ≥ 100 mL/min: 12 mg/kg IV over 24 hours once daily on days -7, -6, -5, -4
- > 12 kg and GFR ≥ 100 mL/min: 375 mg/m2 IV over 24 hours once daily on days -7, -6, -5, -4
- ≤ 12 kg and GFR between 100 mL/min and 60 mL/min: 4.1 AUC using Calvert Formula (Max Dose = 300 mg/m2) IV over 24 hours once daily on days -7, -6, -5, -4
- > 12 kg and GFR between 100 mL/min and 60 mL/min: Use the lowest of either 4.1 AUC using Calvert Formula or 10 mg/kg IV over 24 hours once daily on days -7, -6, -5, -4
- PBSC on day 0
36 Day Cycle
Supportive Therapy, Tandem HSCT #2 (CEM)
- Filgrastim (Neupogen) 5 μg/kg SubQ or IV once daily starting on day 0 and continuing until post-nadir ANC > 2000/μL for 3 consecutive days
36 Day Cycle
Maintenance, 6 Cycles
Chemotherapy,
- Isotretinoin (Accutane) by the following weight-based criteria:
- ≤ 12 kg: 5.33 mg/kg (Round dose to nearest 10 mg) PO twice daily on days 1 through 14
- > 12 kg: 160 mg/m2 (Round dose to nearest 10 mg) PO twice daily on days 1 through 14
28 Day Cycle
References
- COG ANBL0532:Seif AE, Naranjo A, Baker DL, Bunin NJ, Kletzel M, Kretschmar CS, Maris JM, McGrady PW, von Allmen D, Cohn SL, London WB, Park JR, Diller LR, Grupp SA. A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children's Oncology Group study ANBL00P1. Bone Marrow Transplant. 2013 Jul;48(7):947-52. link to original article link to PMC article PubMed
Low-risk
Intermediate-risk, all lines of therapy
COG A3961 regimen
Regimen
Study | Evidence |
---|---|
Baker et al. 2010 (COG A3961) | Non-randomized |
To be completed.
Chemotherapy
- See paper for details
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
COJEC
COJEC: Cisplatin, Oncovin (Vicristine), JM8 (Carboplatin), Etoposide, Cyclophosphamide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pearson et al. 2008 (ENSG5) | 1990-1999 | Phase 3 (E-esc) | OPEC/OJEC | Seems to have superior EFS36 |
Chemotherapy
- Cisplatin (Platinol)
- Vincristine (Oncovin)
- Carboplatin (Paraplatin)
- Etoposide (Vepesid)
- Cyclophosphamide (Cytoxan)
References
- ENSG5: Pearson AD, Pinkerton CR, Lewis IJ, Imeson J, Ellershaw C, Machin D; European Neuroblastoma Study Group; Children's Cancer and Leukaemia Group (CCLG formerly United Kingdom Children's Cancer Study Group). High-dose rapid and standard induction chemotherapy for patients aged over 1 year with stage 4 neuroblastoma: a randomised trial. Lancet Oncol. 2008 Mar;9(3):247-56. link to original article PubMed NCT00365755
- Update: Moreno L, Vaidya SJ, Pinkerton CR, Lewis IJ, Imeson J, Machin D, Pearson AD; European Neuroblastoma Study Group; Children's Cancer and Leukaemia Group (CCLG) (formerly UKCCSG). Long-term follow-up of children with high-risk neuroblastoma: the ENSG5 trial experience. Pediatr Blood Cancer. 2013 Jul;60(7):1135-40. Epub 2012 Dec 31. link to original article PubMed
N5/N6
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Berthold et al. 2020 (NB2004-HR) | 2004-2016 | Phase 3 (C) | N8, then N5/N6 | Did not meet primary endpoint of EFS |
Chemotherapy, N5 cycles
- Vindesine (Eldisine) as follows:
- Cycles 1, 3, 5: 3 mg/m2 IV over 60 minutes once on day 1
- Cisplatin (Platinol) as follows:
- Cycles 1, 3, 5: 40 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 160 mg/m2)
- Etoposide (Vepesid) as follows:
- Cycles 1, 3, 5: 100 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 400 mg/m2)
Chemotherapy, N6 cycles
- Vincristine (Oncovin) as follows:
- Cycles 2, 4, 6: 1.5 mg/m2 IV over 60 minutes once per day on days 1 & 8
- Dacarbazine (DTIC) as follows:
- Cycles 2, 4, 6: 200 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Ifosfamide (Ifex) as follows:
- Cycles 2, 4, 6: 1500 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 7500 mg/m2)
- Doxorubicin (Adriamycin) as follows:
- Cycles 2, 4, 6: 30 mg/m2 IV over 4 hours once per day on days 6 & 7
21-day cycle for 6 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 contains dosing details in supplement PubMed NCT03042429
High-risk, consolidation
Busulfan & Melphalan, then auto HSCT
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ladenstein et al. 2017 (HR-NBL1) | 2002-2010 | Phase 3 (E-esc) | Carboplatin, Etoposide, Melphalan, then auto HSCT | Superior EFS36 |
Note: the abstract does not specify exact days but this schedule is typical; IV dosing was used after a 2007 protocol amendment
Chemotherapy
- Busulfan (Myleran) 0.8 to 1.2 mg/kg IV every 6 hours on days -6 to -3 (16 total doses)
- Melphalan (Alkeran) 140 mg/m2 IV once on day -2
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 dosing details in abstract PubMed NCT01704716
GM-CSF, IL-2, Isotretinoin, Dinutuximab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yu et al. 2010 (COG ANBL0032) | 2001-2009 | Phase 3 (E-RT-esc) | 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.
Targeted therapy
- 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
Immunotherapy
- 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
- Isotretinoin (Accutane) 160 mg/m2/day PO on days 14 to 27
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 dosing details in manuscript PubMed NCT00026312
- Update: Yu AL, Gilman AL, Ozkaynak MF, Naranjo A, Diccianni MB, Gan J, Hank JA, Batova A, London WB, Tenney SC, Smith M, Shulkin BL, Parisi M, Matthay KK, Cohn SL, Maris JM, Bagatell R, Park JR, Sondel PM. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res. 2021 Apr 15;27(8):2179-2189. Epub 2021 Jan 27. link to original article link to PMC article PubMed
Isotretinoin monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Matthay et al. 1999 | 1991-1996 | Phase 3 (E-esc) | No further therapy | Seems to have superior EFS |
Yu et al. 2010 (COG ANBL0032) | 2001-2009 | Phase 3 (C) | GM-CSF, IL-2, Isotretinoin, Dinutuximab | Seems to have inferior OS |
Preceding treatment
- Matthay et al. 1999: HDT with purged auto HSCT versus cisplatin, doxorubicin, etoposide consolidation
Chemotherapy
- Isotretinoin (Accutane) 80 mg/m2 PO twice per day on days 1 to 14
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 dosing details in manuscript 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 dosing details in manuscript PubMed NCT00026312
- Update: Yu AL, Gilman AL, Ozkaynak MF, Naranjo A, Diccianni MB, Gan J, Hank JA, Batova A, London WB, Tenney SC, Smith M, Shulkin BL, Parisi M, Matthay KK, Cohn SL, Maris JM, Bagatell R, Park JR, Sondel PM. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin Cancer Res. 2021 Apr 15;27(8):2179-2189. Epub 2021 Jan 27. link to original article link to PMC article PubMed
Isotretinoin & Dinutuximab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ladenstein et al. 2018 (HR-NBL1) | 2009-2013 | Phase 3 (C) | IL-2, Isotretinoin, Dinutuximab | Did not meet primary endpoint of EFS36 |
Note: this was a second randomization and second cohort of patients enrolled in HR-NBL1.
Preceding treatment
Chemotherapy
Targeted therapy
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 NCT01704716
Relapsed or refractory
Cyclophosphamide monotherapy
Regimen
Study | Evidence |
---|---|
Thurman et al. 1964 | Non-randomized |
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
Study | Evidence |
---|---|
Evans et al. 1969 | Non-randomized |
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
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mody et al. 2017 (COG ANBL1221) | 2013-2015 | Randomized Phase 2, <20 pts (E-switch-ooc) | Irinotecan, Temozolomide, Temsirolimus | Superior ORR |
Note: this dinutuximab dose is based on a mid-protocol revision.
Chemotherapy
- 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
Targeted therapy
- 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 therapy
- Sargramostim (Leukine) 250 mcg/m2 SC once per day on days 6 to 12
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 dosing details in manuscript PubMed NCT01767194
Naxitamab monotherapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Kushner et al. 2018 (Study 12-230) | 2012-2016 | Phase 1 (RT) |
Awaiting publication (Study 201) | 2018-ongoing | Phase 2 (RT) |
Targeted therapy
- Naxitamab (Danyelza) 3 mg/kg (maximum of 150 mg/day) IV once per day on days 1, 3, 5
Supportive therapy
- GM-CSF 250 mcg/m2/day SC once per day on days -4 to 0, then 500 mcg/m2/day SC once per day on days 1 to 5
28-day cycle for 4 cycles until complete response or partial response, followed by 5 additional cycles Subsequent cycles may be repeated every 8 weeks.
References
- Study 12-230: Kushner BH, Cheung IY, Modak S, Basu EM, Roberts SS, Cheung NK. Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma: A Phase 1 Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1729-1735. link to original article link to original article PubMed NCT01757626
- Study 201: NCT03363373