Medulloblastoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

• Craniospinal External beam radiotherapy 18 Gy in 10 daily fractions.
• Posterior Fossa External beam radiotherapy 5.4 Gy in 3 daily fractions prior to the radiation boost.
• Tumor Bed Boost External beam radiotherapy 30.6 Gy in 17 daily fractions.

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, and 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).
  • Pediatric Lomustine Dosing Chart
  • Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age.
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 8, and 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

• Cyclophosphamide (Cytoxan) 1000 mg/m² IV given over 1 hour on Days 1 and 2.
• Mesna (Mesnex) 360 mg/m²/dose IV over 15 to 30 minutes on Days 1 and 2
  • Dose given at least 15 minutes prior to or at the same time as Cyclophosphamide (Cytoxan) and repeated at 4 and 8 hours post Cyclophosphamide (Cytoxan).
  • Can be given via continuous infusion starting 15-30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion.
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, and 8.
  • 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 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

• Craniospinal External beam radiotherapy 18 Gy in 10 daily fractions.
• Posterior Fossa External beam radiotherapy 5.4 Gy in 3 daily fractions prior to the radiation boost.
• Posterior Fossa Boost External beam radiotherapy 30.6 Gy in 17 daily fractions.

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, and 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).
  • Pediatric Lomustine Dosing Chart
  • Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age.
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 8, and 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

• Cyclophosphamide (Cytoxan) 1000 mg/m² IV given over 1 hour on Days 1 and 2.
• Mesna (Mesnex) 360 mg/m²/dose IV over 15 to 30 minutes on Days 1 and 2
  • Dose given at least 15 minutes prior to or at the same time as Cyclophosphamide (Cytoxan) and repeated at 4 and 8 hours post Cyclophosphamide (Cytoxan).
  • Can be given via continuous infusion starting 15-30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion.
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, and 8.
  • 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 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 A

Chemoradiotherapy

XRT

• Craniospinal External beam radiotherapy 36 Gy in 20 daily fractions (Monday - Friday).
• Posterior Fossa Boost External beam radiotherapy 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy).

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, and 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

• Cisplatin (Platinol) 75 mg/m² IV over 60 minutes once on day 1
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1 and 8.
  • Round vincristine down to the nearest 0.1 mg.
• Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 1 hour once on days 2 and 3.
  • Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2.

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 B

Chemoradiotherapy

XRT

• Craniospinal External beam radiotherapy 36 Gy in 20 daily fractions (Monday - Friday).
• Posterior Fossa Boost External beam radiotherapy 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy).

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, and 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 - 4 hours prior to radiation therapy (Total of 30 doses).
  • Carboplatin (Paraplatin) first dose administered on the first day of radiation therapy.
  • Carboplatin (Paraplatin) should be HELD if radiation treatment is not given.
  • Since there are 31 fractions of radiation, No Carboplatin (Paraplatin) should be given prior to the final radiation fraction.

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

• Cisplatin (Platinol) 75 mg/m² IV over 60 minutes once on day 1
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1 and 8.
  • Round vincristine down to the nearest 0.1 mg.
• Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 1 hour once on days 2 and 3.
  • Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2.

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