Difference between revisions of "Medulloblastoma - historical"

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#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327
 
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327
 
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327
 
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327
 +
 +
=Upfront Therapy=
 +
==COGACNS1221 Protocol==
 +
===Induction Therapy (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin)===
 +
Given for cycles 1, 2, & 3
 +
====Chemotherapy====
 +
*[[Vincristine (Oncovin)]] by the following criteria
 +
**Ages 0 to 6.99 months: 1 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
 +
**Ages 7 to 12.99: 1.2 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
 +
**Ages ≥13: 1.5 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
 +
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy
 +
 +
*[[Cyclophosphamide (Cytoxan)]] by the following criteria
 +
**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages 7 to 12.99 months: 640 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages ≥13 months: 800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
 +
*[[Mesna (Mesnex)]] by the following criteria
 +
**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages 7 to 12.99 months: 640 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages ≥13 months: 800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**[[Mesna (Mesnex)]] Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes before [[Cyclophosphamide (Cytoxan)]] with subsequent doses given at 3, 6, 9, & 12 hours after the start of [[Cyclophosphamide (Cytoxan)]]
 +
**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 12 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 +
 +
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 15 & 29
 +
**[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV infused over 30 minutes, then [[Methotrexate (MTX)]] 4500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours
 +
 +
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> IV or PO given at 42, 48 & 54 hours after start of [[Methotrexate (MTX)]] infusion on days 17 & 31
 +
**[[Folinic acid (Leucovorin)]] should be continued until serum [[Methotrexate (MTX)]] levels are less than 0.1 µM
 +
**Can be given as an IV push over a minimum of 3 minutes or by short infusion over 15 to 120 minutes
 +
**See full protocol for dose modifications based on [[Methotrexate (MTX)]] levels
 +
 +
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes (maximum rate of 300 mg/m<sup>2</sup>/hr) once per day on days 43 to 45
 +
**Administer [[Etoposide (Vepesid)]] prior to [[Carboplatin (Paraplatin)]]
 +
 +
*[[Carboplatin (Paraplatin)]] by the following criteria
 +
**Ages 0 to 6.99 months: 133 mg/m<sup>2</sup> IV over 1 hour once per day on days 43 to 45
 +
**Ages 7 to 12.99 months: 160 mg/m<sup>2</sup> IV over 1 hour once per day on days 43 to 45
 +
**Ages ≥13 months: 200 mg/m<sup>2</sup> IV over 1 hour once per day on days 43 to 45
 +
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 46
 +
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 +
 +
'''63 day cycle'''
 +
 +
===Continuation Therapy (Vincristine, CPM, Etoposide, Carboplatin)===
 +
Given for 2 cycles if residual disease noted after Induction
 +
====Chemotherapy====
 +
*[[Vincristine (Oncovin)]] by the following criteria
 +
**Ages 0 to 6.99 months: 1 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
 +
**Ages 7 to 12.99: 1.2 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
 +
**Ages ≥13: 1.5 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
 +
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy
 +
 +
*[[Cyclophosphamide (Cytoxan)]] by the following criteria
 +
**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages 7 to 12.99 months: 640 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages ≥13 months: 800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
 +
*[[Mesna (Mesnex)]] by the following criteria
 +
**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages 7 to 12.99 months: 640 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**Ages ≥13 months: 800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
 +
**[[Mesna (Mesnex)]] Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes before [[Cyclophosphamide (Cytoxan)]] with subsequent doses given at 3, 6, 9, & 12 hours after the start of [[Cyclophosphamide (Cytoxan)]]
 +
**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 12 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
 +
 +
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 to 120 minutes (maximum rate of 300 mg/m<sup>2</sup>/hr) once per day on days 21 to 23
 +
**Administer [[Etoposide (Vepesid)]] prior to [[Carboplatin (Paraplatin)]]
 +
 +
*[[Carboplatin (Paraplatin)]] by the following criteria
 +
**Ages 0 to 6.99 months: 133 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
 +
**Ages 7 to 12.99 months: 160 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
 +
**Ages ≥13 months: 200 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
 +
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 24
 +
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
 +
 +
'''42 day cycle'''
 +
 +
===References===
 +
 +
#'''COG ACNS1221:''' L. Lafay-Cousin, E. Bouffet, D. Strother, V. Rudneva, C. Hawkins, C. Eberhart, C. Horbinski, L. Heier, M. Souweidane, C. Williams-Hughes, A. Onar-Thomas, C. A. Billups, M. Fouladi, P. Northcott, G. Robinson, A. Gajjar.  Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger than 4 Years of Age: A Report of the Children's Oncology Group (ACNS1221). Journal of Clinical Oncology. 2019 Nov 38:3, 243-51. [https://doi.org/10.1200/jco.19.00845 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968798/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31774708/ PubMed] NCT02017964
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[[Category:Medulloblastoma regimens]]
 
[[Category:Medulloblastoma regimens]]

Revision as of 20:43, 28 March 2022

Section editor transclusions

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main medulloblastoma page for current regimens.

4 regimens on this page
5 variants on this page


COGACNS0331 Reduced Dose CSRT/Reduced Volume Boost to Tumor Bed

  • Ages 3-7 Randomized
  • All patients must begin therapy within 31 days of surgery.

Chemoradiotherapy

XRT

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
    • Round vincristine down to the nearest 0.1 mg

7-week course

References

  1. COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735

Maintenance Regimen A

Cycles 1, 2, 4, 5, 7, 8

Chemotherapy

  • Cisplatin (Platinol) 75 mg/m2 IV once on day 1
  • Lomustine (CCNU) 75 mg/m2 PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
    • Dose rounded down to the nearest 0.1 mg
    • Can be given IV push over 1-minute or by infusion via minibag as per institution policy

6-week cycle

References

  1. COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735

Maintenance Regimen B

Cycles 3, 6, and 9

Chemotherapy

6-week course

References

  1. COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735

COGACNS0331 Reduced Dose CSRT/Standard Volume Boost

  • Ages 3-7
  • All patients must begin therapy within 31 days of surgery.

Chemoradiotherapy

XRT

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
    • Round vincristine down to the nearest 0.1 mg

7-week course

References

  1. COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735

Maintenance Regimen A

Cycles 1, 2, 4, 5, 7, 8

Chemotherapy

  • Cisplatin (Platinol) 75 mg/m2 IV once on day 1
  • Lomustine (CCNU) 75 mg/m2 PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
    • Dose rounded down to the nearest 0.1 mg
    • Can be given IV push over 1-minute or by infusion via minibag as per institution policy

6-week cycle

References

  1. COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735


Maintenance Regimen B

Cycles 3, 6, and 9

Chemotherapy

6-week course

References

  1. COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735

COGACNS0332 Regimen C

incomplete regimen - missing isotretinoin dosing

Chemoradiotherapy

XRT

For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)
    • Round vincristine down to the nearest 0.1 mg

6-Week Course

References

  1. COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
  2. COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327

Maintenance Cycle

Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles

Chemotherapy

28-Day Course

References

  1. COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
  2. COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327

COGACNS0332 Regimen D

incomplete regimen - missing isotretinoin dosing

Chemoradiotherapy

XRT

For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage

Chemotherapy

  • Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)
    • Round vincristine down to the nearest 0.1 mg
    • Administer prior to Carboplatin
  • Carboplatin (Paraplatin) 35 mg/m2 IV over 15 minutes given daily 1 to 4 hours prior to radiation therapy (Total of 30 doses)

6-Week Course

  1. COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
  2. COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327

Maintenance Cycle

Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles

Chemotherapy

28-Day Course

References

  1. COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
  2. COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327

Upfront Therapy

COGACNS1221 Protocol

Induction Therapy (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin)

Given for cycles 1, 2, & 3

Chemotherapy

  • Vincristine (Oncovin) by the following criteria
    • Ages 0 to 6.99 months: 1 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
    • Ages 7 to 12.99: 1.2 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
    • Ages ≥13: 1.5 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
    • Can be given IV push over 1-minute or by infusion via minibag as per institution policy
  • Cyclophosphamide (Cytoxan) by the following criteria
    • Ages 0 to 6.99 months: 533 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages 7 to 12.99 months: 640 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages ≥13 months: 800 mg/m2 IV over 1 hour once per day on days 1 to 3
  • Mesna (Mesnex) by the following criteria
    • Ages 0 to 6.99 months: 533 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages 7 to 12.99 months: 640 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages ≥13 months: 800 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Mesna (Mesnex) Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes before Cyclophosphamide (Cytoxan) with subsequent doses given at 3, 6, 9, & 12 hours after the start of Cyclophosphamide (Cytoxan)
    • Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 12 hours after the end of the Cyclophosphamide (Cytoxan) infusion
  • Carboplatin (Paraplatin) by the following criteria
    • Ages 0 to 6.99 months: 133 mg/m2 IV over 1 hour once per day on days 43 to 45
    • Ages 7 to 12.99 months: 160 mg/m2 IV over 1 hour once per day on days 43 to 45
    • Ages ≥13 months: 200 mg/m2 IV over 1 hour once per day on days 43 to 45
  • Filgrastim (Neupogen) 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 46
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

63 day cycle

Continuation Therapy (Vincristine, CPM, Etoposide, Carboplatin)

Given for 2 cycles if residual disease noted after Induction

Chemotherapy

  • Vincristine (Oncovin) by the following criteria
    • Ages 0 to 6.99 months: 1 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
    • Ages 7 to 12.99: 1.2 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
    • Ages ≥13: 1.5 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
    • Can be given IV push over 1-minute or by infusion via minibag as per institution policy
  • Cyclophosphamide (Cytoxan) by the following criteria
    • Ages 0 to 6.99 months: 533 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages 7 to 12.99 months: 640 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages ≥13 months: 800 mg/m2 IV over 1 hour once per day on days 1 to 3
  • Mesna (Mesnex) by the following criteria
    • Ages 0 to 6.99 months: 533 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages 7 to 12.99 months: 640 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Ages ≥13 months: 800 mg/m2 IV over 1 hour once per day on days 1 to 3
    • Mesna (Mesnex) Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes before Cyclophosphamide (Cytoxan) with subsequent doses given at 3, 6, 9, & 12 hours after the start of Cyclophosphamide (Cytoxan)
    • Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 12 hours after the end of the Cyclophosphamide (Cytoxan) infusion
  • Carboplatin (Paraplatin) by the following criteria
    • Ages 0 to 6.99 months: 133 mg/m2 IV over 1 hour once per day on days 21 to 23
    • Ages 7 to 12.99 months: 160 mg/m2 IV over 1 hour once per day on days 21 to 23
    • Ages ≥13 months: 200 mg/m2 IV over 1 hour once per day on days 21 to 23
  • Filgrastim (Neupogen) 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 24
    • ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

42 day cycle

References

  1. COG ACNS1221: L. Lafay-Cousin, E. Bouffet, D. Strother, V. Rudneva, C. Hawkins, C. Eberhart, C. Horbinski, L. Heier, M. Souweidane, C. Williams-Hughes, A. Onar-Thomas, C. A. Billups, M. Fouladi, P. Northcott, G. Robinson, A. Gajjar. Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger than 4 Years of Age: A Report of the Children's Oncology Group (ACNS1221). Journal of Clinical Oncology. 2019 Nov 38:3, 243-51. link to original article link to PMC article PubMed NCT02017964