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	Nicole M. Wood, DO University of Missouri Kansas City, MO, USA LinkedIn

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

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

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Michalski et al. 2021 (COG ACNS0331)	2004-04-30 to 2014-01-06	Phase 3 (E-de-esc)	COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost	Inferior EFS (primary endpoint)

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

Induction

Radiotherapy

Craniospinal External beam radiotherapy 1800 cGy in 10 daily fractions
Posterior Fossa External beam radiotherapy 540 cGy in 3 daily fractions prior to the radiation boost
Tumor Bed Boost External beam radiotherapy 3060 cGy in 17 daily fractions

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 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

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Lomustine (CCNU) 75 mg/m² PO once on day 1, taken 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

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 60 minutes once per day 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, second portion (cycles 3, 6, 9; "Part B")

Mesna (Mesnex) 360 mg/m² IV over 15 to 30 minutes once per day on days 1 & 2
- Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
- Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion

42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)

References

COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth 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. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. link to original article link to PMC article PubMed NCT00085735

COG ACNS0331 Reduced Dose CSRT with Standard Volume Boost

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Michalski et al. 2021 (COG ACNS0331)	2004-04-30 to 2014-01-06	Phase 3 (E-de-esc)	COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost	Inferior EFS (primary endpoint)

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

Induction

Radiotherapy

Craniospinal External beam radiotherapy 1800 cGy in 10 daily fractions
Posterior Fossa External beam radiotherapy 540 cGy in 3 daily fractions prior to the radiation boost
Posterior Fossa Boost External beam radiotherapy 3060 cGy in 17 daily fractions

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 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

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Lomustine (CCNU) 75 mg/m² PO once on day 1, taken 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

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 60 minutes once per day 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, second portion (cycles 3, 6, 9; "Part B")

Mesna (Mesnex) 360 mg/m² IV over 15 to 30 minutes once per day on days 1 & 2
- Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
- Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion

42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)

References

COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth 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. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. link to original article link to PMC article PubMed NCT00085735

COG ACNS0332 Regimen C

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Leary et al. 2021 (COG ACNS0332)	2007-03 to 2018-09	Phase 3 (E-esc)	COG ACNS0332 Protocol A (no carboplatin)	Not reported

Note: incomplete regimen - missing isotretinoin dosing; this arm was closed early for futility.

Induction, Chemoradiotherapy

Radiotherapy

Craniospinal External beam radiotherapy 3600 cGy in 20 daily fractions (Monday - Friday)
Posterior Fossa Boost External beam radiotherapy 1980 cGy in 11 daily fractions (Cumulative dose of 5580 cGy)

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 once per day on days 1, 8, 15, 22, 29, 36, starting within one week of the start of CSRT
- Round vincristine down to the nearest 0.1 mg

6-week course, followed by:

Maintenance

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 once per day on days 1 & 8
- Round vincristine down to the nearest 0.1 mg
Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 1 hour once per day on days 2 & 3
- Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2

28-day cycle for 6 cycles; begin next cycle on day 29 or when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours

References

COG ACNS0332: Leary SES, Packer RJ, Li Y, 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 Oncol. 2021 Sep 1;7(9):1313-1321. link to original article link to PMC article PubMed NCT00392327

COG ACNS0332 Regimen D

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Leary et al. 2021 (COG ACNS0332)	2007-03 to 2018-09	Phase 3 (E-esc)	COG ACNS0332 Protocol A (no carboplatin)	Not reported

Note: incomplete regimen - missing isotretinoin dosing; this arm was closed early for futility.

Induction, Chemoradiotherapy

Radiotherapy

Craniospinal External beam radiotherapy 3600 cGy in 20 daily fractions (Monday - Friday)
Posterior Fossa Boost External beam radiotherapy 1980 cGy in 11 daily fractions (Cumulative dose of 5580 cGy)

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 once per day on days 1, 8, 15, 22, 29, 36, 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 once per day on radiation days, given 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

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 once per day on days 1 & 8
- Round vincristine down to the nearest 0.1 mg
Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 1 hour once per day on days 2 & 3, given at least 24 hours after cisplatin on day 2

28-day cycle for 6 cycles; begin each cycle on day 29 or when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours

References

COG ACNS0332: Leary SES, Packer RJ, Li Y, 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 Oncol. 2021 Sep 1;7(9):1313-1321. link to original article link to PMC article PubMed NCT00392327

All lines of therapy, younger children

COG ACNS1221 Protocol

Study	Dates of enrollment	Evidence
Lafay-Cousin et al. 2019 (COG ACNS1221)	2013-12-12 to 2016-07-07	Phase 2

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

Given for cycles 1, 2, & 3

Chemotherapy

Vincristine (Oncovin) by the following age-based criteria:
- 0 to 6.99 months old: 1 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 15, 29
- 7 to 12.99 months old: 1.2 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 15, 29
- 13 months old or older: 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 15, 29
- 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:
- 0 to 6.99 months old: 533 mg/m² IV over 1 hour once per day on days 1 to 3
- 7 to 12.99 months old: 640 mg/m² IV over 1 hour once per day on days 1 to 3
- 13 months old or older: 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:
- 0 to 6.99 months old: 533 mg/m² IV over 1 hour once per day on days 1 to 3
- 7 to 12.99 months old: 640 mg/m² IV over 1 hour once per day on days 1 to 3
- 13 months old or older: 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 prior to cyclophosphamide with subsequent doses given at 3, 6, 9, & 12 hours after the start of cyclophosphamide
- Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 12 hours after the end of the cyclophosphamide infusion

Chemotherapy

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 4500 mg/m² given by continuous IV infusion over 23.5 hours

Supportive therapy

Leucovorin (Folinic acid) 15 mg/m² IV or PO given at 42, 48 & 54 hours after start of methotrexate infusion on days 17 & 31
- Leucovorin (Folinic acid) should be continued until serum methotrexate 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 levels

Chemotherapy

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, given before carboplatin
Carboplatin (Paraplatin) by the following age-based criteria:
- 0 to 6.99 months old: 133 mg/m² IV over 1 hour once per day on days 43 to 45
- 7 to 12.99 months old: 160 mg/m² IV over 1 hour once per day on days 43 to 45
- 13 months old or older: 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 once per day for at least 7 days or until ANC at least 750/μl, beginning on day 4 & 46
- ANC at least 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:
- 0 to 6.99 months old: 1 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 15, 29
- 7 to 12.99 months old: 1.2 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 15, 29
- 13 months old or older: 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 15, 29
- 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:
- 0 to 6.99 months old: 533 mg/m² IV over 1 hour once per day on days 1 to 3
- 7 to 12.99 months old: 640 mg/m² IV over 1 hour once per day on days 1 to 3
- 13 months old or older: 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:
- 0 to 6.99 months old: 533 mg/m² IV over 1 hour once per day on days 1 to 3
- 7 to 12.99 months old: 640 mg/m² IV over 1 hour once per day on days 1 to 3
- 13 months old or older: 800 mg/m² IV over 1 hour once per day on days 1 to 3
  - Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes prior to cyclophosphamide with subsequent doses given at 3, 6, 9, & 12 hours after the start of cyclophosphamide
  - Dose can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 12 hours after the end of the cyclophosphamide infusion

Chemotherapy

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, given prior to carboplatin
Carboplatin (Paraplatin) by the following age-based criteria:
- 0 to 6.99 months old: 133 mg/m² IV over 1 hour once per day on days 21 to 23
- 7 to 12.99 months old: 160 mg/m² IV over 1 hour once per day on days 21 to 23
- 13 months old or older: 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 once per day for at least 7 days or until ANC at least 750/μl, beginning on days 4 & 24
- ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF

42-day cycle

References

COG ACNS1221: Lafay-Cousin L, Bouffet E, Strother D, Rudneva V, Hawkins C, Eberhart C, Horbinski C, Heier L, Souweidane M, Williams-Hughes C, Onar-Thomas A, Billups CA, Fouladi M, Northcott P, Robinson G, Gajjar A. Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger Than 4 Years of Age: A Report of the Children's Oncology Group (ACNS1221). J Clin Oncol. 2020 Jan 20;38(3):223-231. Epub 2019 Nov 27. link to original article link to PMC article PubMed NCT02017964

Head Start III Regimen D

Study	Dates of enrollment	Evidence
Dhall et al. 2020 (Head Start III)	2003-05 to 2009-12	Non-randomized

Induction

Chemotherapy, first portion (cycles 1 & 3)

Cisplatin (Platinol) 3.5 mg/kg IV once on day 1
Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
Cyclophosphamide (Cytoxan) 65 mg/kg IV once per day on days 2 & 3
Etoposide (Vepesid) 4 mg/kg IV once per day on days 2 & 3
High Dose Methotrexate (MTX) 400 mg/kg IV over 4 hours once on day 3

Supportive therapy, first portion (cycles 1 & 3)

Leucovorin (Folinic acid) 10 mg/m² PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
- Leucovorin (Folinic acid) must be started 24 hours from the beginning of the methotrexate infusion

Chemotherapy, second portion (cycles 2 & 4)

Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
Cyclophosphamide (Cytoxan) 65 mg/kg IV once per day on days 2 & 3
Etoposide (Vepesid) 1.65 mg/kg PO once per day on days 1 to 10
Temozolomide (Temodar) 6.5 mg/kg PO once per day on days 1 to 5

Chemotherapy, third portion (cycle 5)

Cisplatin (Platinol) 3.5 mg/kg IV once on day 1
Cyclophosphamide (Cytoxan) 65 mg/kg IV once per day on days 2 & 3
Etoposide (Vepesid) 4 mg/kg IV once per day on days 2 & 3
High Dose Methotrexate (MTX) 400 mg/kg IV over 4 hours once on day 3

Supportive therapy, third portion (cycle 5)

Leucovorin (Folinic acid) 10 mg/m² PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
- Leucovorin (Folinic acid) must be started 24 hours from the beginning of the methotrexate infusion

5 cycles

Consolidation, Myeloablative Chemotherapy with AuHCR

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

Chemotherapy

Carboplatin (Paraplatin) AUC 7 IV once per day on days 1 to 3
Thiotepa (Thioplex) 300 mg/m² IV once per day on days 1 to 3, given immediately after carboplatin administration
Etoposide (Vepesid) 250 mg/m² IV once per day on days 1 to 3

3-day course

References

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 Oncol. 2020 Dec 18;22(12):1862-1872. link to original article link to PMC article PubMed NCT00392327

HIT-SKK'92 regimen

Regimen

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

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) 200 mg/m² IV once per day on days 43 to 45
Cyclophosphamide (Cytoxan) 800 mg/m² IV once per day on days 1 to 3
Etoposide (Vepesid) 150 mg/m² IV once per day on days 43 to 45
Methotrexate (MTX) 5000 mg/m² IV continuous infusion over 24 hours, started on days 15 & 29 (total dose per cycle: 10,000 mg/m²)
Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 15, 29

CNS treatment

Methotrexate (MTX)

2-month cycle for 3 cycles

References

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 contains dosing details in manuscript PubMed

Baby POG I protocol

Regimen variant #1, 12 months

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

Note: this length of treatment was intended for children 24 to 36 months of age at diagnosis.

Preceding treatment

Surgical resection or biopsy

Chemotherapy, A portion (cycles 1, 2, 4, 5, 7, 8, 10, 11, 13)

Cyclophosphamide (Cytoxan) 65 mg/kg IV over 30 minutes once on day 1
Vincristine (Oncovin) 0.065 mg/kg (maximum dose of 1.5 mg) IV push once per day on days 1 & 8

Chemotherapy, B portion (cycles 3, 6, 9, 12)

Cisplatin (Platinol) 4 mg/kg IV over 6 hours once on day 1
Etoposide (Vepesid) 6.5 mg/kg IV once per day on days 3 & 4

28-day cycle for 13 cycles (1 year)

Subsequent treatment

Adjuvant RT

Regimen variant #2, 24 months

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

Note: this length of treatment was intended for children under 24 months of age at diagnosis.

Preceding treatment

Surgical resection or biopsy

Chemotherapy, A portion (cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19, 20, 22, 23, 25, 26)

Cyclophosphamide (Cytoxan) 65 mg/kg IV over 30 minutes once on day 1
Vincristine (Oncovin) 0.065 mg/kg (maximum dose of 1.5 mg) IV push once per day on days 1 & 8

Chemotherapy, B portion (cycles 3, 6, 9, 12, 15, 18, 21, 24)

Cisplatin (Platinol) 4 mg/kg IV over 6 hours once on day 1
Etoposide (Vepesid) 6.5 mg/kg IV once per day on days 3 & 4

28-day cycle for 26 cycles (2 years)

Subsequent treatment

Adjuvant RT

References

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 contains dosing details in manuscript PubMed

VCP [CCG-921]

VCP: Vincristine, CCNU (Lomustine), Prednisone

Regimen

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

Preceding treatment

Surgery, then adjuvant Vincristine & RT

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15
Lomustine (CCNU) 100 mg/m² IV once on day 1

Glucocorticoid therapy

Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

42-day cycle for 8 cycles

References

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

Regimen

Study	Dates 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

Surgery, then adjuvant radiotherapy

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Lomustine (CCNU) 75 mg/m² PO once on day 0
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 7, 14

8 cycles (see note)

References

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

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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 [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Medulloblastoma|main medulloblastoma page]] for current regimens.
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+The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Medulloblastoma|main medulloblastoma page]] for current regimens.
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 |}
 {{TOC limit|limit=4}}
 =Pediatric Historic Therapy Older Children=
+==COG ACNS0331 Reduced Dose CSRT with Reduced Volume Boost to Tumor Bed==
-==COGACNS0331 Reduced Dose CSRT/Reduced Volume Boost to Tumor Bed==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ Michalski et al. 2021 (COG ACNS0331)]
+|2004-04-30 to 2014-01-06
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[Medulloblastoma#COG_ACNS0331_Standard_Dose_CSRT_with_Reduced_Volume_Boost_to_Tumor_Bed|COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost]]
+| style="background-color:#d73027" |Inferior EFS (primary endpoint)
+|-
+|}
 *Ages 3-7 Randomized
 *All patients must begin therapy within 31 days of surgery.
-===Chemoradiotherapy===
+<div class="toccolours" style="background-color:#ee6b6e">
-====XRT====
+===Induction===
-*Craniospinal [[External beam radiotherapy]] 18 Gy in 10 daily fractions
+<div class="toccolours" style="background-color:#b3e2cd">
-*Posterior Fossa [[External beam radiotherapy]] 5.4 Gy in 3 daily fractions prior to the radiation boost
+====Radiotherapy====
-*Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions
+*Craniospinal [[External beam radiotherapy]] 1800 cGy in 10 daily fractions
+*Posterior Fossa [[External beam radiotherapy]] 540 cGy in 3 daily fractions prior to the radiation boost
+*Tumor Bed Boost [[External beam radiotherapy]] 3060 cGy in 17 daily fractions
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (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)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 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'''
+</div></div><br>
-===Maintenance Regimen A===
+<div class="toccolours" style="background-color:#ee6b6e">
- Cycles 1, 2, 4, 5, 7, 8
+===Maintenance===
-====Chemotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
+*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1, taken 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
@@ Line 36: / Line 53: @@
 **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
+====Chemotherapy, second portion (cycles 3, 6, 9; "Part B")====
-'''6-week cycle'''
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
-===Maintenance Regimen B===
- Cycles 3, 6, and 9
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2
-*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> 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/m<sup>2</sup> (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, second portion (cycles 3, 6, 9; "Part B")====
+*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 1 & 2
+**Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
+**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion
+'''42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)'''
+</div></div></div>
-'''6-week course'''
+===References===
+#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth 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. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34110925/ PubMed] [https://clinicaltrials.gov/study/NCT00085735 NCT00085735]
-=====References=====
+==COG ACNS0331 Reduced Dose CSRT with Standard Volume Boost==
-#'''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. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-==COGACNS0331 Reduced Dose CSRT/Standard Volume Boost==
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ Michalski et al. 2021 (COG ACNS0331)]
+|2004-04-30 to 2014-01-06
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[Medulloblastoma#COG_ACNS0331_Protocol_for_Standard_Dose_CSRT_with_Standard_Volume_Boost|COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost]]
+| style="background-color:#d73027" |Inferior EFS (primary endpoint)
+|-
+|}
 *Ages 3-7
 *All patients must begin therapy within 31 days of surgery.
-===Chemoradiotherapy===
+<div class="toccolours" style="background-color:#ee6b6e">
-====XRT====
+===Induction===
-*Craniospinal [[External beam radiotherapy]] 18 Gy in 10 daily fractions
+<div class="toccolours" style="background-color:#b3e2cd">
-*Posterior Fossa [[External beam radiotherapy]] 5.4 Gy in 3 daily fractions prior to the radiation boost
+====Radiotherapy====
-*Posterior Fossa Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions
+*Craniospinal [[External beam radiotherapy]] 1800 cGy in 10 daily fractions
+*Posterior Fossa [[External beam radiotherapy]] 540 cGy in 3 daily fractions prior to the radiation boost
+*Posterior Fossa Boost [[External beam radiotherapy]] 3060 cGy in 17 daily fractions
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (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)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 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'''
+</div></div><br>
-===Maintenance Regimen A===
+<div class="toccolours" style="background-color:#ee6b6e">
- Cycles 1, 2, 4, 5, 7, 8
+===Maintenance===
-====Chemotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
+*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1, taken 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
@@ Line 79: / Line 109: @@
 **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
+====Chemotherapy, second portion (cycles 3, 6, 9; "Part B")====
-'''6-week cycle'''
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
-===Maintenance Regimen B===
- Cycles 3, 6, and 9
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2
-*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> 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/m<sup>2</sup> (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, second portion (cycles 3, 6, 9; "Part B")====
+*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 1 & 2
+**Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
+**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion
+'''42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)'''
+</div></div></div>
+===References===
+#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth 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. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34110925/ PubMed] [https://clinicaltrials.gov/study/NCT00085735 NCT00085735]
-'''6-week course'''
+==COG ACNS0332 Regimen C==
+<div class="toccolours" style="background-color:#c8a2c8">
-=====References=====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-#'''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. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
-==COGACNS0332 Regimen C==
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-''incomplete regimen - missing isotretinoin dosing''
+!style="width: 20%"|Comparator
-===Chemoradiotherapy===
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-====XRT====
+|-
-*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday)
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ Leary et al. 2021 (COG ACNS0332)]
-*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
+|2007-03 to 2018-09
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Medulloblastoma#COG_ACNS0332_Protocol_A|COG ACNS0332 Protocol A (no carboplatin)]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+|}
+''Note: incomplete regimen - missing isotretinoin dosing; this arm was closed early for futility.''
+<div class="toccolours" style="background-color:#ee6b6e">
+===Induction, Chemoradiotherapy===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*Craniospinal [[External beam radiotherapy]] 3600 cGy in 20 daily fractions (Monday - Friday)
+*Posterior Fossa Boost [[External beam radiotherapy]] 1980 cGy in 11 daily fractions (Cumulative dose of 5580 cGy)
   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/m<sup>2</sup> (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)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15, 22, 29, 36, starting within one week of the start of CSRT
 **Round vincristine '''down''' to the nearest 0.1 mg
+'''6-week course, followed by:'''
-'''6-Week Course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
-===Maintenance Cycle===
+===Maintenance===
-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
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1 & 8
 **Round vincristine '''down''' to the nearest 0.1 mg
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2, 3
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once per day on days 2 & 3
 **[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2
+'''28-day cycle for 6 cycles; begin next cycle on day 29 or when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours'''
-'''28-Day Course'''
+</div></div></div>
+===References===
-=====References=====
+#'''COG ACNS0332:''' Leary SES, Packer RJ, Li Y, 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 Oncol. 2021 Sep 1;7(9):1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34292305/ PubMed] [https://clinicaltrials.gov/study/NCT00392327 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 Regimen D==
-#'''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
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-==COGACNS0332 Regimen D==
+!style="width: 20%"|Study
-''incomplete regimen - missing isotretinoin dosing''
+!style="width: 20%"|Dates of enrollment
-===Chemoradiotherapy===
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-====XRT====
+!style="width: 20%"|Comparator
-*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday)
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ Leary et al. 2021 (COG ACNS0332)]
+|2007-03 to 2018-09
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Medulloblastoma#COG_ACNS0332_Protocol_A|COG ACNS0332 Protocol A (no carboplatin)]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+|}
+''Note: incomplete regimen - missing isotretinoin dosing; this arm was closed early for futility.''
+<div class="toccolours" style="background-color:#ee6b6e">
+===Induction, Chemoradiotherapy===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*Craniospinal [[External beam radiotherapy]] 3600 cGy in 20 daily fractions (Monday - Friday)
+*Posterior Fossa Boost [[External beam radiotherapy]] 1980 cGy in 11 daily fractions (Cumulative dose of 5580 cGy)
   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/m<sup>2</sup> (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)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15, 22, 29, 36, 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/m<sup>2</sup> IV over 15 minutes given daily 1 to 4 hours prior to radiation therapy (Total of 30 doses)
+*[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes once per day on radiation days, given 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'''
-'''6-Week Course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
-===Maintenance Cycle===
+===Maintenance===
-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
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1 & 8
 **Round vincristine '''down''' to the nearest 0.1 mg
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2 and 3
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once per day on days 2 & 3, given at least 24 hours after cisplatin on day 2
-**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2
+'''28-day cycle for 6 cycles; begin each cycle on day 29 or when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours'''
+</div></div></div>
-'''28-Day Course'''
+===References===
+#'''COG ACNS0332:''' Leary SES, Packer RJ, Li Y, 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 Oncol. 2021 Sep 1;7(9):1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34292305/ PubMed] [https://clinicaltrials.gov/study/NCT00392327 NCT00392327]
-=====References=====
+=All lines of therapy, younger children=
-#'''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 ACNS1221 Protocol==
-===Induction Therapy (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin)===
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968798/ Lafay-Cousin et al. 2019 (COG ACNS1221)]
+|2013-12-12 to 2016-07-07
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#ee6b6e">
+===Induction, (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin)===
   Given for cycles 1, 2, & 3
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] by the following criteria
+*[[Vincristine (Oncovin)]] by the following age-based 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)
+**0 to 6.99 months old: 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29
-**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)
+**7 to 12.99 months old: 1.2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29
-**Ages ≥13: 1.5 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
+**13 months old or older: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29
 **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:
-*[[Cyclophosphamide (Cytoxan)]] by the following criteria
+**0 to 6.99 months old: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
-**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
+**7 to 12.99 months old: 640 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
+**13 months old or older: 800 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
+====Supportive therapy====
+*[[Mesna (Mesnex)]] by the following age-based criteria:
-*[[Mesna (Mesnex)]] by the following criteria
+**0 to 6.99 months old: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
-**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
+**7 to 12.99 months old: 640 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
+**13 months old or older: 800 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 prior to cyclophosphamide with subsequent doses given at 3, 6, 9, & 12 hours after the start of cyclophosphamide
-**[[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 and finished no sooner than 12 hours after the end of the cyclophosphamide infusion
-**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====
 *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
+**[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV infused over 30 minutes, then 4500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours
+====Supportive therapy====
-*[[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
+*[[Leucovorin (Folinic acid)]] 15 mg/m<sup>2</sup> IV or PO given at 42, 48 & 54 hours after start of methotrexate infusion on days 17 & 31
-**[[Folinic acid (Leucovorin)]] should be continued until serum [[Methotrexate (MTX)]] levels are less than 0.1 µM
+**[[Leucovorin (Folinic acid)]] should be continued until serum methotrexate 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
+**See full protocol for dose modifications based on methotrexate levels
+====Chemotherapy====
-*[[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
+*[[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, given before carboplatin
-**Administer [[Etoposide (Vepesid)]] prior to [[Carboplatin (Paraplatin)]]
+*[[Carboplatin (Paraplatin)]] by the following age-based criteria:
+**0 to 6.99 months old: 133 mg/m<sup>2</sup> IV over 1 hour once per day on days 43 to 45
-*[[Carboplatin (Paraplatin)]] by the following criteria
+**7 to 12.99 months old: 160 mg/m<sup>2</sup> IV over 1 hour once per day on days 43 to 45
-**Ages 0 to 6.99 months: 133 mg/m<sup>2</sup> IV over 1 hour once per day on days 43 to 45
+**13 months old or older: 200 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
+====Supportive therapy====
-**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 once per day for at least 7 days or until ANC at least 750/μl, beginning on day 4 & 46
+**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 46
+'''63-day cycle'''
-**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
-'''63 day cycle'''
+===Continuation, Therapy (Vincristine, CPM, Etoposide, Carboplatin)===
-===Continuation Therapy (Vincristine, CPM, Etoposide, Carboplatin)===
   Given for 2 cycles if residual disease noted after Induction
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] by the following criteria
+*[[Vincristine (Oncovin)]] by the following age-based 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)
+**0 to 6.99 months old: 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29
-**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)
+**7 to 12.99 months old: 1.2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29
-**Ages ≥13: 1.5 mg/m<sup>2</sup> IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
+**13 months old or older: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29
 **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:
-*[[Cyclophosphamide (Cytoxan)]] by the following criteria
+**0 to 6.99 months old: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
-**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
+**7 to 12.99 months old: 640 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
+**13 months old or older: 800 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
+====Supportive therapy====
+*[[Mesna (Mesnex)]] by the following age-based criteria:
-*[[Mesna (Mesnex)]] by the following criteria
+**0 to 6.99 months old: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
-**Ages 0 to 6.99 months: 533 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3
+**7 to 12.99 months old: 640 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
+**13 months old or older: 800 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
+***Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes prior to cyclophosphamide with subsequent doses given at 3, 6, 9, & 12 hours after the start of cyclophosphamide
-**[[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)]]
+***Dose can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 12 hours after the end of the cyclophosphamide infusion
-**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====
+*[[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, given prior to carboplatin
-*[[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
+*[[Carboplatin (Paraplatin)]] by the following age-based criteria:
-**Administer [[Etoposide (Vepesid)]] prior to [[Carboplatin (Paraplatin)]]
+**0 to 6.99 months old: 133 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
+**7 to 12.99 months old: 160 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
-*[[Carboplatin (Paraplatin)]] by the following criteria
+**13 months old or older: 200 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
-**Ages 0 to 6.99 months: 133 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
+====Supportive therapy====
-**Ages 7 to 12.99 months: 160 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 once per day for at least 7 days or until ANC at least 750/μl, beginning on days 4 & 24
-**Ages ≥13 months: 200 mg/m<sup>2</sup> IV over 1 hour once per day on days 21 to 23
+**ANC at least 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
+'''42-day cycle'''
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 24
+</div></div></div>
-**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
-'''42 day cycle'''
 ===References===
+#'''COG ACNS1221:''' Lafay-Cousin L, Bouffet E, Strother D, Rudneva V, Hawkins C, Eberhart C, Horbinski C, Heier L, Souweidane M, Williams-Hughes C, Onar-Thomas A, Billups CA, Fouladi M, Northcott P, Robinson G, Gajjar A. Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger Than 4 Years of Age: A Report of the Children's Oncology Group (ACNS1221). J Clin Oncol. 2020 Jan 20;38(3):223-231. Epub 2019 Nov 27. [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] [https://clinicaltrials.gov/study/NCT02017964 NCT02017964]
-#'''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
+==Head Start III Regimen D==
+<div class="toccolours" style="background-color:#c8a2c8">
-==HIT-SKK'92 {{#subobject:ea894c|Regimen=1}}==
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746930/ Dhall et al. 2020 (Head Start III)]
+|2003-05 to 2009-12
+| style="background-color:#91cf61" |Non-randomized
 |-
-|[[#top|back to top]]
 |}
+<div class="toccolours" style="background-color:#ee6b6e">
+===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, first portion (cycles 1 & 3)====
+*[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1
+*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
+*[[Cyclophosphamide (Cytoxan)]] 65 mg/kg IV once per day on days 2 & 3
+*[[Etoposide (Vepesid)]] 4 mg/kg IV once per day on days 2 & 3
+*High Dose [[Methotrexate (MTX)]] 400 mg/kg IV over 4 hours once on day 3
+====Supportive therapy, first portion (cycles 1 & 3)====
+*[[Leucovorin (Folinic acid)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
+**[[Leucovorin (Folinic acid)]] must be started 24 hours from the beginning of the methotrexate infusion
+====Chemotherapy, second portion (cycles 2 & 4)====
+*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
+*[[Cyclophosphamide (Cytoxan)]] 65 mg/kg IV once per day on days 2 & 3
+*[[Etoposide (Vepesid)]] 1.65 mg/kg PO once per day on days 1 to 10
+*[[Temozolomide (Temodar)]] 6.5 mg/kg PO once per day on days 1 to 5
+====Chemotherapy, third portion (cycle 5)====
+*[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1
+*[[Cyclophosphamide (Cytoxan)]] 65 mg/kg IV once per day on days 2 & 3
+*[[Etoposide (Vepesid)]] 4 mg/kg IV once per day on days 2 & 3
+*High Dose [[Methotrexate (MTX)]] 400 mg/kg IV over 4 hours once on day 3
+====Supportive therapy, third portion (cycle 5)====
+*[[Leucovorin (Folinic acid)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
+**[[Leucovorin (Folinic acid)]] must be started 24 hours from the beginning of the methotrexate infusion
+'''5 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Consolidation, Myeloablative Chemotherapy with AuHCR===
+*Patients with no evidence of disease (NED) after induction or second look surgery.
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 7 IV once per day on days 1 to 3
+*[[Thiotepa (Thioplex)]] 300 mg/m<sup>2</sup> IV once per day on days 1 to 3, given immediately after carboplatin administration
+*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''3-day course'''
+</div></div></div>
+===References===
+#'''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 Oncol. 2020 Dec 18;22(12):1862-1872. [https://doi.org/10.1093/neuonc/noaa102 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746930/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32304218/ PubMed] [https://clinicaltrials.gov/study/NCT00392327 NCT00392327]
+==HIT-SKK'92 regimen {{#subobject:ea894c|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:9134b2|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 25%"|Study
+!style="width: 33%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.nejm.org/doi/10.1056/NEJMoa042176 Rutkowski et al. 2005]
+|[https://doi.org/10.1056/NEJMoa042176 Rutkowski et al. 2005]
+|1992-1997
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Surgical_resection|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]]
+*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup> IV once per day on days 43 to 45
-*[[Cyclophosphamide (Cytoxan)]]
+*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 to 3
-*[[Etoposide (Vepesid)]]
+*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 43 to 45
+*[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 15 & 29 (total dose per cycle: 10,000 mg/m<sup>2</sup>)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
+====CNS treatment====
 *[[Methotrexate (MTX)]]
-*[[Vincristine (Oncovin)]]
+'''2-month cycle for 3 cycles'''
-====References====
+</div></div>
-# 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. [https://www.nejm.org/doi/10.1056/NEJMoa042176 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15758008 PubMed]
+===References===
-==Baby POG I {{#subobject:852402|Regimen=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. [https://doi.org/10.1056/NEJMoa042176 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15758008/ PubMed]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==Baby POG I protocol {{#subobject:852402|Regimen=1}}==
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #1, 12 months {{#subobject:1a3d99|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1056/NEJM199306173282401 Duffner et al. 1993]
+|1986-1990
+| style="background-color:#91cf61" |Non-randomized
 |-
-|[[#top|back to top]]
 |}
-===Protocol {{#subobject:1a3d99|Variant=1}}===
+''Note: this length of treatment was intended for children 24 to 36 months of age at diagnosis.''
-{| class="wikitable" style="width: 40%; text-align:center;"
+<div class="toccolours" style="background-color:#cbd5e8">
-!style="width: 25%"|Study
+====Preceding treatment====
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+*[[Surgery#Surgical_resection|Surgical resection]] or biopsy
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, A portion (cycles 1, 2, 4, 5, 7, 8, 10, 11, 13)====
+*[[Cyclophosphamide (Cytoxan)]] 65 mg/kg IV over 30 minutes once on day 1
+*[[Vincristine (Oncovin)]] 0.065 mg/kg (maximum dose of 1.5 mg) IV push once per day on days 1 & 8
+====Chemotherapy, B portion (cycles 3, 6, 9, 12)====
+*[[Cisplatin (Platinol)]] 4 mg/kg IV over 6 hours once on day 1
+*[[Etoposide (Vepesid)]] 6.5 mg/kg IV once per day on days 3 & 4
+'''28-day cycle for 13 cycles (1 year)'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Adjuvant [[#Radiation_therapy|RT]]
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
+===Regimen variant #2, 24 months {{#subobject:1a3249|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.nejm.org/doi/10.1056/NEJM199306173282401 Duffner et al. 1993]
+|[https://doi.org/10.1056/NEJM199306173282401 Duffner et al. 1993]
+|1986-1990
 | style="background-color:#91cf61" |Non-randomized
 |-
 |}
-''Total duration of treatment is 12 to 24 months.''
+''Note: this length of treatment was intended for children under 24 months of age at diagnosis.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Surgical_resection|Surgical resection]] or biopsy
-====Chemotherapy, part 1====
+</div>
-*[[Cyclophosphamide (Cytoxan)]]
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Vincristine (Oncovin)]]
+====Chemotherapy, A portion (cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19, 20, 22, 23, 25, 26)====
-'''28-day cycle for 2 cycles, alternating with part 2'''
+*[[Cyclophosphamide (Cytoxan)]] 65 mg/kg IV over 30 minutes once on day 1
-====Chemotherapy, part 2====
+*[[Vincristine (Oncovin)]] 0.065 mg/kg (maximum dose of 1.5 mg) IV push once per day on days 1 & 8
-*[[Cisplatin (Platinol)]]
+====Chemotherapy, B portion (cycles 3, 6, 9, 12, 15, 18, 21, 24)====
-*[[Etoposide (Vepesid)]]
+*[[Cisplatin (Platinol)]] 4 mg/kg IV over 6 hours once on day 1
-'''28-day cycle for 1 cycle, alternating with part 1'''
+*[[Etoposide (Vepesid)]] 6.5 mg/kg IV once per day on days 3 & 4
-====References====
+'''28-day cycle for 26 cycles (2 years)'''
-# 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. [https://www.nejm.org/doi/10.1056/NEJM199306173282401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8388548 PubMed]
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Subsequent treatment====
+*Adjuvant [[#Radiation_therapy|RT]]
+</div></div>
+===References===
+# 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. [https://doi.org/10.1056/NEJM199306173282401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8388548/ PubMed]
-==CCG-921{{#subobject:3dy31n|Regimen=1}}==
+==VCP [CCG-921] {{#subobject:3dy31n|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#ee6b6e">
 ===Regimen {{#subobject:ytacgn|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 310: / Line 458: @@
 |1986-1992
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#8-in-1_88|8-in-1]]
+|[[#8-in-1_888|8-in-1]]
 | style="background-color:#1a9850" |Superior PFS
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[Surgery#Surgical_resection|Surgery]], then Vincristine & RT
+*[[Surgery#Surgical_resection|Surgery]], then adjuvant [[#Vincristine_.26_RT_888|Vincristine & RT]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 *[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> IV once on day 1
+====Glucocorticoid therapy====
 *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14
-'''6-week cycle for 8 cycles'''
+'''42-day cycle for 8 cycles'''
-====References====
+</div></div>
-#'''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. [https://doi.org/10.1200/jco.1999.17.3.832 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10071274/ PubMed]
+===References===
+#'''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. [https://doi.org/10.1200/jco.1999.17.3.832 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10071274/ PubMed]
-==COG A9961 {{#subobject:3d292d|Regimen=1}}==
+==COG A9961 regimen {{#subobject:3d292d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#ee6b6e">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:2067d9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 341: / Line 490: @@
 |1996-2000
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin.2C_Cyclophosphamide.2C_Vincristine_99|Cisplatin, Cyclophosphamide, Vincristine]]
+|[[#Cisplatin.2C_Cyclophosphamide.2C_Vincristine_999|Cisplatin, Cyclophosphamide, Vincristine]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
 ''Note: neither the cycle length nor the exact dosing instructions for vincristine are clear from the manuscript.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[Surgery#Surgical_resection|Surgery]], then radiotherapy
+*[[Surgery#Surgical_resection|Surgery]], then adjuvant [[Regimen_classes#Radiotherapy-based_regimen|radiotherapy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
@@ Line 353: / Line 505: @@
 *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 7, 14
 '''8 cycles (see note)'''
+</div></div>
 ===References===
-# '''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. [https://doi.org/10.1200/JCO.2006.06.4980 link to original article] '''contains partially verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16943538 PubMed] NCT00002875
+# '''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. [https://doi.org/10.1200/JCO.2006.06.4980 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16943538/ PubMed] [https://clinicaltrials.gov/study/NCT00002875 NCT00002875]
 [[Category:Medulloblastoma regimens]]
 [[Category:Historical regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Pediatric neurologic neoplasms]]

Difference between revisions of "Medulloblastoma - historical"

Latest revision as of 01:23, 26 June 2024

Pediatric Historic Therapy Older Children

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

Induction

Radiotherapy

Chemotherapy

Maintenance

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Supportive therapy, second portion (cycles 3, 6, 9; "Part B")

References

COG ACNS0331 Reduced Dose CSRT with Standard Volume Boost

Induction

Radiotherapy

Chemotherapy

Maintenance

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Supportive therapy, second portion (cycles 3, 6, 9; "Part B")

References

COG ACNS0332 Regimen C

Induction, Chemoradiotherapy

Radiotherapy

Chemotherapy

Maintenance

Chemotherapy

References

COG ACNS0332 Regimen D

Induction, Chemoradiotherapy

Radiotherapy

Chemotherapy

Maintenance

Chemotherapy

References

All lines of therapy, younger children

COG ACNS1221 Protocol

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

Chemotherapy

Supportive therapy

Chemotherapy

Supportive therapy

Chemotherapy

Supportive therapy

Continuation, Therapy (Vincristine, CPM, Etoposide, Carboplatin)

Chemotherapy

Supportive therapy

Chemotherapy

Supportive therapy

References

Head Start III Regimen D

Induction

Chemotherapy, first portion (cycles 1 & 3)

Supportive therapy, first portion (cycles 1 & 3)

Chemotherapy, second portion (cycles 2 & 4)

Chemotherapy, third portion (cycle 5)

Supportive therapy, third portion (cycle 5)

Consolidation, Myeloablative Chemotherapy with AuHCR

Chemotherapy

References

HIT-SKK'92 regimen

Regimen

Preceding treatment

Chemotherapy

CNS treatment

References

Baby POG I protocol

Regimen variant #1, 12 months

Preceding treatment

Chemotherapy, A portion (cycles 1, 2, 4, 5, 7, 8, 10, 11, 13)

Chemotherapy, B portion (cycles 3, 6, 9, 12)

Subsequent treatment

Regimen variant #2, 24 months

Preceding treatment

Chemotherapy, A portion (cycles 1, 2, 4, 5, 7, 8, 10, 11, 13, 14, 16, 17, 19, 20, 22, 23, 25, 26)

Chemotherapy, B portion (cycles 3, 6, 9, 12, 15, 18, 21, 24)

Subsequent treatment

References

VCP [CCG-921]

Regimen