Medulloblastoma - historical

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Nikki M. Wood, DO
University of Missouri
Kansas City, MO

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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


Pediatric Historic Therapy Older Children

COG ACNS0331 Reduced Dose CSRT/Reduced Volume Boost to Tumor Bed

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

Chemoradiotherapy

Radiotherapy

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)
  • 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
  • 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

Supportive therapy

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

COG ACNS0331 Reduced Dose CSRT/Standard Volume Boost

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

Chemoradiotherapy

Radiotherapy

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)
  • 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
  • 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

Supportive therapy

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

COG ACNS0332 Regimen C

incomplete regimen - missing isotretinoin dosing

Chemoradiotherapy

Radiotherapy

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

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 ACNS0332 Regimen D

incomplete regimen - missing isotretinoin dosing

Chemoradiotherapy

Radiotherapy

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

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

All lines of therapy, younger children

COG ACNS1221 Protocol

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

Given for cycles 1, 2, & 3

Chemotherapy

  • Vincristine (Oncovin) by the following age-based 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 months: 1.2 mg/m2 IV once per day on days 1, 15, 29 (maximum dose of 2 mg)
    • Ages ≥13 months: 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 age-based 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

Supportive therapy

  • Mesna (Mesnex) by the following age-based 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

Chemotherapy

Supportive therapy

Chemotherapy

  • 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

Supportive therapy

  • 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 age-based 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 months: 1.2 mg/m2 IV once per day on days 1, 15, 29 (maximum dose of 2 mg)
    • Ages ≥13 months: 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 age-based 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

Supportive therapy

  • 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

Chemotherapy

  • 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

Supportive therapy

  • 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

Head Start III Regimen D

Induction Cycles 1 & 3

Chemotherapy

Supportive therapy

15-day course

Induction Cycles 2 & 4

Chemotherapy

15-day course

Induction Cycle 5

Chemotherapy

Supportive therapy

15-day course

Myeloablative Chemotherapy with AuHCR

  • Patients with no evidence of disease (NED) after induction or second look surgery.

Chemotherapy

3-day course

References

  1. Head Start III: Dhall G, O'Neil SH, Ji L, Haley K, Whitaker AM, Nelson MD, Gilles F, Gardner SL, Allen JC, Cornelius AS, Pradhan K, Garvin JH, Olshefski RS, Hukin J, Comito M, Goldman S, Atlas MP, Walter AW, Sands S, Sposto R, Finlay JL. Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial. Neuro-Oncology 2020 Apr 18: 22(12);1862-1872 link to original article link to PubMed link to PMC article NCT00392327

HIT-SKK'92

Regimen

Study Years of enrollment Evidence
Rutkowski et al. 2005 1992-1997 Non-randomized

Preceding treatment

Chemotherapy

References

  1. Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10;352(10):978-86. link to original article PubMed

Baby POG I

Protocol

Study Years of enrollment Evidence
Duffner et al. 1993 1986-1990 Non-randomized

Total duration of treatment is 12 to 24 months.

Preceding treatment

Chemotherapy, part 1

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

Chemotherapy, part 2

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

CCG-921

VCP: Vincristine, CCNU (Lomustine), Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Zeltzer et al. 1999 (CCG-921) 1986-1992 Phase 3 (C) 8-in-1 Superior PFS

Preceding treatment

Chemotherapy

Glucocorticoid therapy

6-week cycle for 8 cycles

References

  1. CCG-921: Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999 Mar;17(3):832-45. link to original article contains dosing details in manuscript PubMed


COG A9961

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Packer et al. 2006 (COG A9961) 1996-2000 Phase 3 (C) Cisplatin, Cyclophosphamide, Vincristine Did not meet primary endpoint of EFS

Note: neither the cycle length nor the exact dosing instructions for vincristine are clear from the manuscript.

Preceding treatment

Chemotherapy

8 cycles (see note)

References

  1. COG A9961: Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. link to original article contains dosing details in manuscript PubMed NCT00002875