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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

Pediatric Historic Therapy

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, 43 (Once a week starting one week after CSRT begins)
  • Round vincristine down to the nearest 0.1 mg

7-week course

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, 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

Maintenance Regimen B

Cycles 3, 6, and 9

Chemotherapy

• Cyclophosphamide (Cytoxan) 1000 mg/m² IV given over 1 hour on Days 1, 2
• Mesna (Mesnex) 360 mg/m² IV over 15 to 30 minutes on Days 1, 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 to 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, 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, 43 (Once a week starting one week after CSRT begins)
  • Round vincristine down to the nearest 0.1 mg

7-week course

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, 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

Maintenance Regimen B

Cycles 3, 6, and 9

Chemotherapy

• Cyclophosphamide (Cytoxan) 1000 mg/m² IV given over 1 hour on Days 1, 2
• Mesna (Mesnex) 360 mg/m² IV over 15 to 30 minutes on Days 1, 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 to 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, 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 C

incomplete regimen - missing isotretinoin dosing

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, 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

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, 8
  • Round vincristine down to the nearest 0.1 mg
• Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 1 hour once on days 2, 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 D

incomplete regimen - missing isotretinoin dosing

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, 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)
  • 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

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, 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

COG ACNS1221 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

• High Dose Methotrexate (MTX) 5000 mg/m² IV over 24 hours on days 15 & 29
  • Methotrexate (MTX) 500 mg/m² IV infused over 30 minutes, then Methotrexate (MTX) 4500 mg/m² given by continuous IV infusion over 23.5 hours

• Folinic acid (Leucovorin) 15 mg/m² 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/m² IV over 60 to 120 minutes (maximum rate of 300 mg/m²/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/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

• Etoposide (Vepesid) 150 mg/m² IV over 60 to 120 minutes (maximum rate of 300 mg/m²/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/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

Adjuvant Therapy

Cyclophosphamide & Vincristine/Cisplatin & Etoposide

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Protocol

Study	Evidence
Duffner et al. 1993	Non-randomized

Total duration of treatment is 12 to 24 months.

Preceding treatment

• Surgical resection or biopsy

Chemotherapy, part 1

• Cyclophosphamide (Cytoxan)
• Vincristine (Oncovin)

28-day cycle for 2 cycles, alternating with part 2

Chemotherapy, part 2

• Cisplatin (Platinol)
• Etoposide (Vepesid)

28-day cycle for 1 cycle, alternating with part 1

References

1. Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. link to original article PubMed