Difference between revisions of "Medulloblastoma"
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*Ages 3+ | *Ages 3+ | ||
*All patients must begin therapy within 31 days of surgery. | *All patients must begin therapy within 31 days of surgery. | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol=== | ===Protocol=== | ||
− | ''Note: this protocol is given in two parts, induction and maintenance. The induction portion lasts 7 weeks, and the maintenance portion lasts for 54 weeks, consisting of alternating A cycles and B cycles (AAB-AAB-AAB).'' | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ Michalski et al. 2021 (COG ACNS0331)] | ||
+ | |4/30/2004-1/6/2014 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-de-esc) | ||
+ | |[[#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:#eeee01" |Non-inferior EFS (primary endpoint)<br>EFS60: 82.5% vs 80.5%<br>(HR 0.97, 94% CI 1.32) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this protocol is given in two parts, induction and maintenance. The induction portion lasts 7 weeks, and the maintenance portion lasts for 54 weeks, consisting of alternating A cycles and B cycles (AAB-AAB-AAB). The non-inferiority comparison was one-sided, with the upper bound reported here.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy, induction portion==== | ====Radiotherapy, induction portion==== | ||
*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | *Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | ||
Line 39: | Line 55: | ||
***Dose rounded '''down''' to the nearest 0.1 mg | ***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 | ***Can be given IV push over 1-minute or by infusion via minibag as per institution policy | ||
− | |||
====Chemotherapy, maintenance part B==== | ====Chemotherapy, maintenance part B==== | ||
*[[Cyclophosphamide (Cytoxan)]] as follows: | *[[Cyclophosphamide (Cytoxan)]] as follows: | ||
Line 52: | Line 67: | ||
***Dose is 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)]] | ***Dose is 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 | ***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 | ||
− | |||
'''42-day cycle for 9 cycles; this is given in an AAB-AAB-AAB sequence''' | '''42-day cycle for 9 cycles; this is given in an AAB-AAB-AAB sequence''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy | + | #'''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. Epub 2021 Jun 10. [https://doi.org/10.1200/JCO.20.02730 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34110925/ PubMed] NCT00085735 |
− | |||
==COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost== | ==COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost== | ||
*Ages 3+ | *Ages 3+ | ||
*All patients must begin therapy within 31 days of surgery. | *All patients must begin therapy within 31 days of surgery. | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol=== | ===Protocol=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ Michalski et al. 2021 (COG ACNS0331)] | ||
+ | |4/30/2004-1/6/2014 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#COG_ACNS0331_Protocol_for_Standard_Dose_CSRT_with_Reduced_Volume_Boost_to_Tumor_Bed|COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost to Tumor Bed]] | ||
+ | | style="background-color:#eeee01" |Non-inferior EFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy, induction portion==== | ====Radiotherapy, induction portion==== | ||
*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | *Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | ||
Line 88: | Line 117: | ||
**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 | **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 | ||
'''6-week course''' | '''6-week course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy | + | #'''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. Epub 2021 Jun 10. [https://doi.org/10.1200/JCO.20.02730 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34110925/ PubMed] NCT00085735 |
− | |||
==COG ACNS0332 Protocol A== | ==COG ACNS0332 Protocol A== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol=== | ===Protocol=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ Leary et al. 2021 (COG ACNS0332)] | ||
+ | |3/2007-9/2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#COG_ACNS0332_Protocol_B|COG ACNS0332 Protocol B (with carboplatin)]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy, induction==== | ====Radiotherapy, induction==== | ||
*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday) | *Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday) | ||
Line 107: | Line 152: | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once on days 2, 3, '''given at least 24 hours after cisplatin on day 2''' | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once 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 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours''' | '''28-day cycle for 6 cycles; 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''' | ||
+ | </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] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34292305/ PubMed] NCT00392327 | |
− | #'''COG ACNS0332:''' Leary SES, Packer RJ, | ||
==COG ACNS0332 Protocol B== | ==COG ACNS0332 Protocol B== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol=== | ===Protocol=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ Leary et al. 2021 (COG ACNS0332)] | ||
+ | |3/2007-9/2018 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#COG_ACNS0332_Protocol_A|COG ACNS0332 Protocol A (no carboplatin)]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy, induction==== | ====Radiotherapy, induction==== | ||
*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday) | *Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday) | ||
Line 131: | Line 192: | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 2 & 3, '''given at least 24 hours after cisplatin on day 2''' | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes 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 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours''' | '''28-day cycle for 6 cycles; 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''' | ||
+ | </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] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34292305/ PubMed] NCT00392327 | |
− | #'''COG ACNS0332:''' Leary SES, Packer RJ, | + | =Upfront Therapy, Younger Children= |
− | |||
− | =Upfront Therapy Younger Children= | ||
==COG ACNS0334 Protocol A== | ==COG ACNS0334 Protocol A== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Induction, 21-Day Cycle for 3 Cycles=== | ===Induction, 21-Day Cycle for 3 Cycles=== | ||
− | ====Chemotherapy | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years 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://clinicaltrials.gov/ct2/show/NCT00336024 Awaiting publication (COG ACNS0334)] | ||
+ | |2007-NR | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#COG_ACNS0334_Protocol_B|COG ACNS0334 Protocol B (HD-MTX)]] | ||
+ | | style="background-color:#d3d3d3" |TBD | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once per day on days 1, 8, 15 | *[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once per day on days 1, 8, 15 | ||
*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration of [[Etoposide (Vepesid)]] is 0.4 mg/ml) IV over 60 minutes once per day on days 1, 2, 3 | *[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration of [[Etoposide (Vepesid)]] is 0.4 mg/ml) IV over 60 minutes once per day on days 1, 2, 3 | ||
Line 155: | Line 231: | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily starting 24-36 hours after Cisplatin infusion and continue until ANC > 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL. | *[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily starting 24-36 hours after Cisplatin infusion and continue until ANC > 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL. | ||
'''21-day cycle for 3 cycles''' | '''21-day cycle for 3 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Consolidation, 28-day cycle for 3 cycles=== | ===Consolidation, 28-day cycle for 3 cycles=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years 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://clinicaltrials.gov/ct2/show/NCT00336024 Awaiting publication (COG ACNS0334)] | ||
+ | |2007-NR | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#COG_ACNS0334_Protocol_B|COG ACNS0334 Protocol B (HD-MTX)]] | ||
+ | | style="background-color:#d3d3d3" |TBD | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, Autologous Transplant==== | ====Chemotherapy, Autologous Transplant==== | ||
*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours once per day on days 1 & 2 | *[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours once per day on days 1 & 2 | ||
Line 163: | Line 255: | ||
** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns | ** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns | ||
*PBSC on day 4 | *PBSC on day 4 | ||
− | |||
====Supportive therapy, Autologous Transplant==== | ====Supportive therapy, Autologous Transplant==== | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day, starting on day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL | *[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day, starting on day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL | ||
**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion | **If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion | ||
'''28-day cycle for 3 cycles''' | '''28-day cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''COG ACNS0334:''' | + | #'''COG ACNS0334:''' NCT00336024 |
==COG ACNS0334 Protocol B== | ==COG ACNS0334 Protocol B== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Induction=== | ===Induction=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years 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://clinicaltrials.gov/ct2/show/NCT00336024 Awaiting publication (COG ACNS0334)] | ||
+ | |2007-NR | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#COG_ACNS0334_Protocol_A|COG ACNS0334 Protocol A (no HD-MTX)]] | ||
+ | | style="background-color:#d3d3d3" |TBD | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, induction==== | ====Chemotherapy, induction==== | ||
'''3 Cycles''' | '''3 Cycles''' | ||
Line 198: | Line 305: | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily starting on day D (24-36 hours after Cisplatin infusion) and continue until ANC > 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL. | *[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily starting on day D (24-36 hours after Cisplatin infusion) and continue until ANC > 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL. | ||
'''21-day course, followed by:''' | '''21-day course, followed by:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Consolidation=== | ===Consolidation=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Years 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://clinicaltrials.gov/ct2/show/NCT00336024 Awaiting publication (COG ACNS0334)] | ||
+ | |2007-NR | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#COG_ACNS0334_Protocol_A|COG ACNS0334 Protocol A (no HD-MTX)]] | ||
+ | | style="background-color:#d3d3d3" |TBD | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, Autologous Transplan==== | ====Chemotherapy, Autologous Transplan==== | ||
'''3 Cycles''' | '''3 Cycles''' | ||
Line 206: | Line 330: | ||
** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns | ** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns | ||
*PBSC on day 4 | *PBSC on day 4 | ||
− | |||
====Supportive therapy, Autologous Transplant==== | ====Supportive therapy, Autologous Transplant==== | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL | *[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL | ||
**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion | **If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion | ||
'''28-day Cycle''' | '''28-day Cycle''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''COG ACNS0334:''' | + | #'''COG ACNS0334:''' NCT00336024 |
==Head Start III Protocol D2== | ==Head Start III Protocol D2== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Protocol=== | ===Protocol=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Years 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)] | ||
+ | |5/2003-12/2009 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy, induction cycles 1 & 3==== | ====Chemotherapy, induction cycles 1 & 3==== | ||
*[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1 | *[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1 | ||
Line 232: | Line 367: | ||
*[[Temozolomide (Temodar)]] 6.5 mg/kg PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 6.5 mg/kg PO once per day on days 1 to 5 | ||
'''15-day cycles''' | '''15-day cycles''' | ||
− | |||
====Chemotherapy, induction cycle 5==== | ====Chemotherapy, induction cycle 5==== | ||
*[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1 | *[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1 | ||
Line 247: | Line 381: | ||
*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV once daily on Day 1 to 3 | *[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV once daily on Day 1 to 3 | ||
'''3-day course''' | '''3-day course''' | ||
+ | </div></div> | ||
===References=== | ===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 | + | #'''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] NCT00392327 |
− | + | ==SJMB-96 Protocol High Risk== | |
− | ==SJMB 96 Protocol High Risk== | + | <div class="toccolours" style="background-color:#eeeeee"> |
===Protocol=== | ===Protocol=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Years of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(06)70867-1 Gajjar et al. 2006 (SJMB-96)] | ||
+ | |10/1996-5/2003 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
'''2 Cycles''' | '''2 Cycles''' | ||
Line 260: | Line 406: | ||
**PBSC harvest after first [[Topotecan (Hycamtin)]] course, or second [[Topotecan (Hycamtin)]] course if first PBSC is inadequate | **PBSC harvest after first [[Topotecan (Hycamtin)]] course, or second [[Topotecan (Hycamtin)]] course if first PBSC is inadequate | ||
'''14-day Cycle''' | '''14-day Cycle''' | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
*Craniospinal axis [[External beam radiotherapy]] by the following staging: | *Craniospinal axis [[External beam radiotherapy]] by the following staging: | ||
Line 266: | Line 411: | ||
**M<sub>2</sub> - M<sub>3</sub>: 36 to 39.6 Gy in 18 to 22 daily fractions | **M<sub>2</sub> - M<sub>3</sub>: 36 to 39.6 Gy in 18 to 22 daily fractions | ||
***See protocol for additional details on dose | ***See protocol for additional details on dose | ||
− | |||
*Posterior fossa [[External beam radiotherapy]] 55.8 Gy in 31 daily fractions | *Posterior fossa [[External beam radiotherapy]] 55.8 Gy in 31 daily fractions | ||
**Local boost [[External beam radiotherapy]] to 59.4 Gy in 33 daily fractions at investigator's option for residual tumor measuring > 1.5 cm<sup>2</sup> | **Local boost [[External beam radiotherapy]] to 59.4 Gy in 33 daily fractions at investigator's option for residual tumor measuring > 1.5 cm<sup>2</sup> | ||
*6-week rest period following radiotherapy | *6-week rest period following radiotherapy | ||
'''~ 6 week duration''' | '''~ 6 week duration''' | ||
− | |||
====Chemotherapy, High Dose with PBSC support==== | ====Chemotherapy, High Dose with PBSC support==== | ||
'''4 Cycles''' | '''4 Cycles''' | ||
Line 284: | Line 427: | ||
*PBSC Infusion on day 0 | *PBSC Infusion on day 0 | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC > 2000/μL for 2 consecutive days. | *[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC > 2000/μL for 2 consecutive days. | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #''' | + | #'''SJMB-96:''' Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820 [https://doi.org/10.1016/S1470-2045(06)70867-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17012043/ PubMed] NCT00003211 |
− | ##''' | + | ##'''Toxicity update:''' Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118 [https://doi.org/10.1200/JCO.2008.13.5293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18309946/ PubMed] |
− | + | ==SJMB-96 Protocol Average Risk== | |
− | ==SJMB 96 Protocol Average Risk== | + | <div class="toccolours" style="background-color:#eeeeee"> |
===Protocol=== | ===Protocol=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Years of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(06)70867-1 Gajjar et al. 2006 (SJMB-96)] | ||
+ | |10/1996-5/2003 | ||
+ | | style="background-color:#91cf61" |Non-randomized | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Growth factor therapy==== | ====Growth factor therapy==== | ||
*[[Filgrastim (Neupogen)]] 10 mcg/kg SubQ or IV (per institutional policy) mobilization prior to PBSC harvest | *[[Filgrastim (Neupogen)]] 10 mcg/kg SubQ or IV (per institutional policy) mobilization prior to PBSC harvest | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*Craniospinal axis [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | *Craniospinal axis [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | ||
− | |||
*Posterior fossa [[External beam radiotherapy]] 55.8 Gy in 31 daily fractions | *Posterior fossa [[External beam radiotherapy]] 55.8 Gy in 31 daily fractions | ||
*6 week rest period following radiotherapy | *6 week rest period following radiotherapy | ||
'''~ 6 week duration''' | '''~ 6 week duration''' | ||
− | |||
====Chemotherapy, High Dose with PBSC support==== | ====Chemotherapy, High Dose with PBSC support==== | ||
'''4 Cycles''' | '''4 Cycles''' | ||
Line 314: | Line 465: | ||
*PBSC Infusion on day 0 | *PBSC Infusion on day 0 | ||
*[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC > 2000/μL for 2 consecutive days. | *[[Filgrastim (Neupogen)]] 5 mcg/kg SubQ or IV (per institutional policy) once daily beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC > 2000/μL for 2 consecutive days. | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #''' | + | #'''SJMB-96:''' Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820 [https://doi.org/10.1016/S1470-2045(06)70867-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17012043/ PubMed] NCT00003211 |
− | ##''' | + | ##'''Toxicity update:''' Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118 [https://doi.org/10.1200/JCO.2008.13.5293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18309946/ PubMed] |
− | |||
− | |||
− | |||
[[Category:Medulloblastoma regimens]] | [[Category:Medulloblastoma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Pediatric neurologic neoplasms]] | [[Category:Pediatric neurologic neoplasms]] |
Revision as of 17:44, 1 March 2023
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Guidelines
EANO/EURACAN
- 2019: Franceschi et al. EANO–EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma
Upfront Therapy Older Children
COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost to Tumor Bed
- Ages 3+
- All patients must begin therapy within 31 days of surgery.
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Michalski et al. 2021 (COG ACNS0331) | 4/30/2004-1/6/2014 | Phase 3 (E-de-esc) | COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost | Non-inferior EFS (primary endpoint) EFS60: 82.5% vs 80.5% (HR 0.97, 94% CI 1.32) |
Note: this protocol is given in two parts, induction and maintenance. The induction portion lasts 7 weeks, and the maintenance portion lasts for 54 weeks, consisting of alternating A cycles and B cycles (AAB-AAB-AAB). The non-inferiority comparison was one-sided, with the upper bound reported here.
Radiotherapy, induction portion
- Craniospinal External beam radiotherapy 23.4 Gy in 13 daily fractions
- Tumor Bed Boost External beam radiotherapy 30.6 Gy in 17 daily fractions
Chemotherapy, induction portion
- 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, followed by:
Chemotherapy, maintenance part A
- Cisplatin (Platinol) as follows:
- Cycles 1, 2, 4, 5, 7, 8: 75 mg/m2 IV once on day 1
- Lomustine (CCNU) as follows:
- Cycles 1, 2, 4, 5, 7, 8: 75 mg/m2 PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
- Pediatric Lomustine Dosing Chart
- Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
- Cycles 1, 2, 4, 5, 7, 8: 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) as follows:
- Cycles 1, 2, 4, 5, 7, 8: 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
- Cycles 1, 2, 4, 5, 7, 8: 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
Chemotherapy, maintenance part B
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 3, 6, 9: 1000 mg/m2 IV given over 1 hour on Days 1, 2
- Vincristine (Oncovin) as follows:
- Cycles 3, 6, 9: 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
- Cycles 3, 6, 9: 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8
Supportive therapy, maintenance part B
- Mesna (Mesnex) as follows:
- Cycles 3, 6, 9: 360 mg/m2 IV over 15 to 30 minutes on Days 1, 2
- Dose is 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
- Cycles 3, 6, 9: 360 mg/m2 IV over 15 to 30 minutes on Days 1, 2
42-day cycle for 9 cycles; this is given in an AAB-AAB-AAB sequence
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. Epub 2021 Jun 10. link to original article link to PMC article PubMed NCT00085735
COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost
- Ages 3+
- All patients must begin therapy within 31 days of surgery.
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Michalski et al. 2021 (COG ACNS0331) | 4/30/2004-1/6/2014 | Phase 3 (C) | COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost to Tumor Bed | Non-inferior EFS |
Radiotherapy, induction portion
- Craniospinal External beam radiotherapy 23.4 Gy in 13 daily fractions
- Posterior Fossa Boost External beam radiotherapy 30.6 Gy in 17 daily fractions
Chemotherapy, induction portion
- 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, followed by:
Chemotherapy, maintenance part A (Cycles 1, 2, 4, 5, 7, 8)
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
- Pediatric Lomustine Dosing Chart
- Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Dose rounded down to the nearest 0.1 mg
- Can be given IV push over 1-minute or by infusion via minibag as per institution policy
6-week cycle
Chemotherapy, maintenance part B (Cycles 3, 6, 9)
- 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, maintenance part B (Cycles 3, 6, 9)
- Mesna (Mesnex) 360 mg/m2 IV over 15 to 30 minutes on Days 1, 2
- Dose given at least 15 minutes prior to or at the same time as Cyclophosphamide (Cytoxan) and repeated at 4 and 8 hours post Cyclophosphamide (Cytoxan)
- Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
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. Epub 2021 Jun 10. link to original article link to PMC article PubMed NCT00085735
COG ACNS0332 Protocol A
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Leary et al. 2021 (COG ACNS0332) | 3/2007-9/2018 | Phase 3 (C) | COG ACNS0332 Protocol B (with carboplatin) | Did not meet primary endpoint of EFS |
Radiotherapy, induction
- Craniospinal External beam radiotherapy 36 Gy in 20 daily fractions (Monday - Friday)
- Posterior Fossa Boost External beam radiotherapy 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
Chemotherapy, induction
- 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, followed by:
Chemotherapy, maintenance
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once per day on days 1, 8
- Round vincristine down to the nearest 0.1 mg
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 60 minutes once 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 and when ANC ≥ 750/μL, platelets ≥ 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 Protocol B
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Leary et al. 2021 (COG ACNS0332) | 3/2007-9/2018 | Phase 3 (E-esc) | COG ACNS0332 Protocol A (no carboplatin) | Did not meet primary endpoint of EFS |
Radiotherapy, induction
- Craniospinal External beam radiotherapy 36 Gy in 20 daily fractions (Monday - Friday)
- Posterior Fossa Boost External beam radiotherapy 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
Chemotherapy, induction
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once per day on days 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 once per day, given 1 to 4 hours prior to radiation therapy (Total of 30 doses)
- First dose administered on the first day of radiation therapy
- Should be HELD if radiation treatment is not given
- Since there are 31 fractions of radiation, No carboplatin should be given prior to the final radiation fraction
6-week course, followed by:
Chemotherapy, maintenance
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once per day on days 1 & 8
- Round vincristine down to the nearest 0.1 mg
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 60 minutes 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 and when ANC ≥ 750/μL, platelets ≥ 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
Upfront Therapy, Younger Children
COG ACNS0334 Protocol A
Induction, 21-Day Cycle for 3 Cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (COG ACNS0334) | 2007-NR | Phase 3 (C) | COG ACNS0334 Protocol B (HD-MTX) | TBD |
Chemotherapy
- Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once per day on days 1, 8, 15
- Etoposide (Vepesid) 2.5 mg/kg (maximum concentration of Etoposide (Vepesid) is 0.4 mg/ml) IV over 60 minutes once per day on days 1, 2, 3
- Begin Etoposide (Vepesid) infusion 1 hour before the Cyclophosphamide (Cytoxan) or Cisplatin (Platinol) infusions
- Cyclophosphamide (Cytoxan) 60 mg/kg IV over 60 minutes once per day on days 1 & 2, given with hyperhydration and mesna
- Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
- Cisplatin (Platinol) 3.5 mg/kg IV infusion over 6 hours on Day 3
- Cisplatin (Platinol) doses may require the use of mannitol to augment hydration and diuresis
- Must reduce urine specific gravity to ≤1.010 prior to starting of [[Cisplatin (Platinol)]
Supportive therapy,
- Mesna (Mesnex) 60 mg/kg IV on Days 1, 2, of which the total daily Mesna (Mesnex) dose is administered in 5 equally divided doses of 12 mg/kg:
- Dose 1: Initial bolus dose of mesna may be administered before or at the same time as the Cyclophosphamide (Cytoxan)
- Dose 2: A 3-hour infusion of Mesna (Mesnex) immediately following the Cyclophosphamide (Cytoxan) infusion (Hours 2 - 5)
- Dose 3-5: 3 subsequent Mesna (Mesnex) bolus doses are given at hours 6, 9, 12, or by institutional protocol
- Mesna (Mesnex) may also be given as a 24-hour continuous infusion starting 30 minutes before cyclophosphamide and finishing no sooner than 12 hours after the end of the cyclophosphamide infusion, or by institutional protocol
- Filgrastim (Neupogen) 5 mcg/kg SubQ or IV (per institutional policy) once daily starting 24-36 hours after Cisplatin infusion and continue until ANC > 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL.
21-day cycle for 3 cycles
Consolidation, 28-day cycle for 3 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (COG ACNS0334) | 2007-NR | Phase 3 (C) | COG ACNS0334 Protocol B (HD-MTX) | TBD |
Chemotherapy, Autologous Transplant
- Carboplatin (Paraplatin) 17 mg/kg IV over 2 hours once per day on days 1 & 2
- If corrected GFR is < 100 ml/min/1.73m2, the Carboplatin (Paraplatin) dose should be calculated using the modified Calvert formula
- Thiotepa (Thioplex) 10 mg/kg IV over 2 hours once per day on days 1 & 2, given immediately following Carboplatin (Paraplatin) administration
- Skincare, frequent bathing, and linen changes during Thiotepa (Thioplex) administration are important and required to avoid chemical skin burns
- PBSC on day 4
Supportive therapy, Autologous Transplant
- Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day, starting on day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL
- If Filgrastim (Neupogen) is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion
28-day cycle for 3 cycles
References
- COG ACNS0334: NCT00336024
COG ACNS0334 Protocol B
Induction
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (COG ACNS0334) | 2007-NR | Phase 3 (E-esc) | COG ACNS0334 Protocol A (no HD-MTX) | TBD |
Chemotherapy, induction
3 Cycles
- Vincristine (Oncovin) 0.05 mg/kg (maximum single dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15
- High Dose Methotrexate (MTX) 400 mg/kg (20 gram maximum) IV over 4 hours on day 1
- Etoposide (Vepesid) 2.5 mg/kg (maximum concentration of Etoposide (Vepesid) is 0.4 mg/ml) IV over 1 hour once daily on days A, B, C
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Begin Etoposide (Vepesid) infusion 1 hour before the Cyclophosphamide or CIS platin infusions
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day over 1 hour on days A, B
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
- Cisplatin (Platinol) 3.5 mg/kg IV infusion over 6 hours on day C
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Cisplatin (Platinol) doses may require use of mannitol to augment hydration and diuresis
- Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
Supportive therapy, induction
- Folinic acid (Leucovorin) 10 mg/m2 PO or IV every 6 hours until serum Methotrexate (MTX) levels are less than 0.1 micromolar
- Folinic acid (Leucovorin) must be started 24 hours from the beginning of the Methotrexate (MTX) infusion
- Mesna (Mesnex) 12 mg/kg IV on days A, B as described below:
- Dose 1:Initial bolus dose of Mesna (Mesnex) may be administered before or at the same time as the Cyclophosphamide (Cytoxan)
- Dose 2:A 3 hour infusion of Mesna (Mesnex) immediately following the Cyclophosphamide (Cytoxan) infusion
- Dose 3 to 5: 3 Subsequent Mesna (Mesnex) bolus doses given at hours 6, 9, 12 or by institutional protocol
- Mesna (Mesnex) 60 mg/kg/day may also be given as a 24 hour continuous infusion by institutional protocol
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Filgrastim (Neupogen) 5 mcg/kg SubQ or IV (per institutional policy) once daily starting on day D (24-36 hours after Cisplatin infusion) and continue until ANC > 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL.
21-day course, followed by:
Consolidation
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (COG ACNS0334) | 2007-NR | Phase 3 (E-esc) | COG ACNS0334 Protocol A (no HD-MTX) | TBD |
Chemotherapy, Autologous Transplan
3 Cycles
- Carboplatin (Paraplatin) 17 mg/kg IV over 2 hours given daily on Days 1 & 2
- If corrected GFR is < 100 ml/min/1.73m2, the Carboplatin (Paraplatin) dose should be calculated using the modified Calvert formula
- Thiotepa (Thioplex) 10 mg/kg IV over 2 hours once daily on Days 1 & 2 immediately following Carboplatin (Paraplatin) administration
- Skincare, frequent bathing, and linen changes during Thiotepa (Thioplex) administration are important and required to avoid chemical skin burns
- PBSC on day 4
Supportive therapy, Autologous Transplant
- Filgrastim (Neupogen) 5 mcg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL
- If Filgrastim (Neupogen) is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion
28-day Cycle
References
- COG ACNS0334: NCT00336024
Head Start III Protocol D2
Protocol
Study | Years of enrollment | Evidence |
---|---|---|
Dhall et al. 2020 (Head Start III) | 5/2003-12/2009 | Non-randomized |
Chemotherapy, induction 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 on days 1, 8, & 15
- Cyclophosphamide (Cytoxan) 55 mg/kg IV once on days 2 & 3
- Etoposide (Vepesid) 4 mg/kg IV once daily on days 2 & 3
- High Dose Methotrexate (MTX) 270 mg/kg IV over 4 hours once on day 3
Supportive therapy, induction cycles 1 & 3
- Folinic acid (Leucovorin) 10 mg/m2 PO or IV every 6 hours until serum Methotrexate (MTX) levels are less than 0.1 micromolar
- Folinic acid (Leucovorin) must be started 24 hours from the beginning of the Methotrexate (MTX) infusion
15-day cycle
Chemotherapy, induction cycles 2 & 4
- Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV once on days 1, 8, & 15
- Cyclophosphamide (Cytoxan) 55 mg/kg IV once on days 2 & 3
- Etoposide (Vepesid) 1.65 mg/kg PO once daily on Day 1 to 10
- Temozolomide (Temodar) 6.5 mg/kg PO once per day on days 1 to 5
15-day cycles
Chemotherapy, induction cycle 5
- Cisplatin (Platinol) 3.5 mg/kg IV once on day 1
- Cyclophosphamide (Cytoxan) 55 mg/kg IV once on days 2 & 3
- Etoposide (Vepesid) 4 mg/kg IV once daily on days 2 & 3
- High Dose Methotrexate (MTX) 270 mg/kg IV over 4 hours once on day 3
Supportive therapy, induction cycle 5
- Folinic acid (Leucovorin) 10 mg/m2 PO or IV every 6 hours until serum Methotrexate (MTX) levels are less than 0.1 micromolar
- Folinic acid (Leucovorin) must be started 24 hours from the beginning of the Methotrexate (MTX) infusion
15-day course; patients with no evidence of disease (NED) after induction or second look surgery proceed to:
Chemotherapy, myeloablative with autologous stem cell rescue
- Carboplatin (Paraplatin) AUC of 7/day once daily on days 1 to 3
- Thiotepa (Thioplex) 300 mg/m2 IV once daily on Days 1 to 3 immediately following Carboplatin (Paraplatin) administration
- Etoposide (Vepesid) 250 mg/m2 IV once daily on Day 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
SJMB-96 Protocol High Risk
Protocol
Study | Years of enrollment | Evidence |
---|---|---|
Gajjar et al. 2006 (SJMB-96) | 10/1996-5/2003 | Non-randomized |
Chemotherapy
2 Cycles
- Topotecan (Hycamtin) 5.5 mg/m2 IV over 4 hours once per day on days 1 to 5
- Day 1 Topotecan (Hycamtin) plasma concentration will be used to adjust the dose (see full protocol?)
Supportive therapy
- Filgrastim (Neupogen) 10 mcg/kg SubQ or IV (per institutional policy) mobilization prior to PBSC harvest
- PBSC harvest after first Topotecan (Hycamtin) course, or second Topotecan (Hycamtin) course if first PBSC is inadequate
14-day Cycle
Radiotherapy
- Craniospinal axis External beam radiotherapy by the following staging:
- M0 - M1: 36 Gy in 18 daily fractions
- M2 - M3: 36 to 39.6 Gy in 18 to 22 daily fractions
- See protocol for additional details on dose
- Posterior fossa External beam radiotherapy 55.8 Gy in 31 daily fractions
- Local boost External beam radiotherapy to 59.4 Gy in 33 daily fractions at investigator's option for residual tumor measuring > 1.5 cm2
- 6-week rest period following radiotherapy
~ 6 week duration
Chemotherapy, High Dose with PBSC support
4 Cycles
- Amifostine (Ethyol) 600 mg/m2 IV push over 1 minute given 5 minutes prior to Cisplatin (Platinol) infusion and 3 hours into Cisplatin (Platinol) infusion on day -4
- Cisplatin (Platinol) 75 mg/m2 IV over 6 hours on day -4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push per day on day -4
- Cyclophosphamide (Cytoxan) 2000 mg/m2 IV infusion over 1 hour on days -3, -2
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push per day on day 6
Supportive therapy
- Mesna (Mesnex) 500 mg/m2 IV push 15 minutes prior to Cyclophosphamide (Cytoxan) infusion on days -3, -2
- Mesna (Mesnex) 1500 mg/m2 IV continuous infusion on days -3, -2
- PBSC Infusion on day 0
- Filgrastim (Neupogen) 5 mcg/kg SubQ or IV (per institutional policy) once daily beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC > 2000/μL for 2 consecutive days.
28-day cycles
References
- SJMB-96: Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820 link to original article PubMed NCT00003211
- Toxicity update: Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118 link to original article PubMed
SJMB-96 Protocol Average Risk
Protocol
Study | Years of enrollment | Evidence |
---|---|---|
Gajjar et al. 2006 (SJMB-96) | 10/1996-5/2003 | Non-randomized |
Growth factor therapy
- Filgrastim (Neupogen) 10 mcg/kg SubQ or IV (per institutional policy) mobilization prior to PBSC harvest
Radiotherapy
- Craniospinal axis External beam radiotherapy 23.4 Gy in 13 daily fractions
- Posterior fossa External beam radiotherapy 55.8 Gy in 31 daily fractions
- 6 week rest period following radiotherapy
~ 6 week duration
Chemotherapy, High Dose with PBSC support
4 Cycles
- Amifostine (Ethyol) 600 mg/m2 IV push over 1 minute given 5 minutes prior to Cisplatin (Platinol) infusion and 3 hours into Cisplatin (Platinol) infusion on day -4
- Cisplatin (Platinol) 75 mg/m2 IV over 6 hours on day -4
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push per day on day -4
- Cyclophosphamide (Cytoxan) 2000 mg/m2 IV infusion over 1 hour on days -3, -2
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push per day on day 6
Supportive medications
- Mesna (Mesnex) 500 mg/m2 IV push 15 minutes prior to Cyclophosphamide (Cytoxan) infusion on days -3, -2
- Mesna (Mesnex) 1500 mg/m2 IV continuous infusion on days -3, -2
- PBSC Infusion on day 0
- Filgrastim (Neupogen) 5 mcg/kg SubQ or IV (per institutional policy) once daily beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC > 2000/μL for 2 consecutive days.
28-day cycles
References
- SJMB-96: Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820 link to original article PubMed NCT00003211
- Toxicity update: Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118 link to original article PubMed