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| − | <span id="BackToTop"></span> | + | ==Carboplatin & Paclitaxel (CP) & Nivolumab {{#subobject:3a6hg7|Regimen=1}}== |
| − | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | + | CP & Nivolumab: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, Nivolumab |
| − | [[#top|Back to Top]] | + | <div class="toccolours" style="background-color:#eeeeee"> |
| − | </div>
| + | ===Regimen variant #1, 5/175/360 {{#subobject:59hhq7|Variant=1}}=== |
| − | {{#lst:Section editor transclusions|peds-neuro}}
| + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
| − | ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Medulloblastoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
| + | !style="width: 20%"|Study |
| − | {| class="wikitable" style="float:right; margin-right: 5px;"
| + | !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/PMC9844511/ Forde et al. 2022 (CheckMate 816)] |
| | + | {| class="wikitable" style="margin:auto; color:black; background-color:#d3d3d3" |
| | + | |[[File:HopeAI.png|link=https://hemonc.org|alt=Alt text|Title=text|frameless|150px|center]] |
| | + | |- |
| | + | |Click to learn more! |
| | + | |- |
| | + | |} |
| | + | |2017-2019 |
| | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
| | + | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|CVb]]<br>1c. [[#Cisplatin_.26_Docetaxel_.28DC.29|DC]] |
| | + | | style="background-color:#1a9850" |Superior EFS (co-primary endpoint)<br>Median EFS: 31.6 vs 20.8 mo<br>(HR 0.63, 97.38% CI 0.43-0.91)<br><br>Superior pCR rate (co-primary endpoint)<br>pCR rate: 24% vs 2.2%<br>(OR 13.94, 99% CI 3.49-55.75) |
| | |- | | |- |
| − | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
| |
| − | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
| |
| | |} | | |} |
| − | {{TOC limit|limit=4}}
| + | ''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.'' |
| − | =Guidelines=
| + | <div class="toccolours" style="background-color:#fdcdac"> |
| − | ==EANO/EURACAN==
| + | ====Biomarker eligibility criteria==== |
| − | *'''2019:''' Franceschi et al. [https://doi.org/10.1016/S1470-2045(19)30669-2 EANO–EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma]
| + | *CheckMate 816: No sensitizing EGFR or ALK mutations |
| − | =Upfront Therapy Older Children=
| + | </div></div> |
| − | ==COG ACNS0331 Protocol; Standard Dose CSRT/Reduced Volume Boost to Tumor Bed==
| |
| − | *Ages 3+
| |
| − | *All patients must begin therapy within 31 days of surgery.
| |
| − | ===Protocol===
| |
| − | ====Radiotherapy, induction portion====
| |
| − | *Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions
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| − | *Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions
| |
| − | ====Chemotherapy, induction portion====
| |
| − | *[[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)
| |
| − | **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/m<sup>2</sup> IV once on day 1
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| − | *[[Lomustine (CCNU)]] as follows:
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| − | **Cycles 1, 2, 4, 5, 7, 8: 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)
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| − | ***[[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)]] as follows:
| |
| − | **Cycles 1, 2, 4, 5, 7, 8: 1.5 mg/m<sup>2</sup> (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
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| − | | |
| − | ====Chemotherapy, maintenance part B====
| |
| − | *[[Cyclophosphamide (Cytoxan)]] as follows:
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| − | **Cycles 3, 6, 9: 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2
| |
| − | *[[Vincristine (Oncovin)]] as follows:
| |
| − | **Cycles 3, 6, 9: 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, maintenance part B (Cycles 3, 6, 9)====
| |
| − | *[[Mesna (Mesnex)]] as follows:
| |
| − | **Cycles 3, 6, 9: 360 mg/m<sup>2</sup> 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
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| − | | |
| − | '''42-day cycle for 9 cycles'''
| |
| − | ===References===
| |
| − | #'''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
| |
| − | ==COG ACNS0331 Protocol; Standard Dose CSRT/Standard Volume Boost==
| |
| − | *Ages 3+
| |
| − | *All patients must begin therapy within 31 days of surgery.
| |
| − | ===Protocol===
| |
| − | ====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/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)
| |
| − | **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/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)
| |
| − | **[[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/m<sup>2</sup> (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/m<sup>2</sup> IV given over 1 hour 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
| |
| − | **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/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
| |
| − | '''6-week course'''
| |
| − | ===References===
| |
| − | #'''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
| |
| − | ==COG ACNS0332 Protocol A==
| |
| − | ===Protocol===
| |
| − | ====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/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)
| |
| − | **Round vincristine '''down''' to the nearest 0.1 mg
| |
| − | '''6-week course, followed by:'''
| |
| − | ====Chemotherapy, maintenance====
| |
| − | *[[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 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 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:''' 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
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| − | #'''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 ACNS0332 Protocol B==
| |
| − | ===Protocol===
| |
| − | ====Radiotherapy, induction====
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| − | *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/m<sup>2</sup> (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
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| − | *[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes once per day, given 1 to 4 hours prior to radiation therapy (Total of 30 doses)
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| − | **First dose administered on the first day of radiation therapy
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| − | **Should be '''HELD''' if radiation treatment is not given
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| − | **Since there are 31 fractions of radiation, No carboplatin should be given prior to the final radiation fraction
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| − | '''6-week course, followed by:'''
| |
| − | ====Chemotherapy, maintenance====
| |
| − | *[[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 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 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:''' 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
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| − | | |
| − | =Upfront Therapy Younger Children=
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| − | ==COG ACNS0334 Regimen A==
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| − | ===Protocol===
| |
| − | ====Chemotherapy, induction====
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| − | *[[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
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| − | *[[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
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| − | **Begin [[Etoposide (Vepesid)]] infusion 1 hour before the [[Cyclophosphamide (Cytoxan)]] or [[Cisplatin (Platinol)]] infusions
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| − | *[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV over 60 minutes once per day on days 1 & 2, given with hyperhydration and Mesna
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| − | **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
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| − | **[[Cisplatin (Platinol)]] doses may require the use of mannitol to augment hydration and diuresis
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| − | **Must reduce urine specific gravity to ≤1.010 prior to starting of [[Cisplatin (Platinol)]
| |
| − | ====Supportive therapy, induction====
| |
| − | *[[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)]]
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| − | **Dose 2: A 3-hour infusion of [[Mesna (Mesnex)]] immediately following the [[Cyclophosphamide (Cytoxan)]] infusion (Hours 2 - 5)
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| − | **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 μg/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 μg/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'''
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| − | ====Chemotherapy, consolidation====
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| − | *[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours once per day on days 1 & 2
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| − | ** If corrected GFR is < 100 ml/min/1.73m<sup>2</sup>, 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
| |
| − | ====Supportive therapy, consolidation==== | |
| − | *[[Filgrastim (Neupogen)]] 5 μg/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:''' P.D. Aridgides, G. Kang, C. Mazewski, T.E. Merchant. Outcomes after Radiation Therapy for Very Young Children with High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG ACNS0334. Radiation Oncology 105, no. 1 (September 1, 2019)[https://doi.org/10.1016/j.ijrobp.2019.06.602 link to original article] NCT00336024
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| − | ==COG ACNS0334 Regimen B==
| |
| − | ===Induction===
| |
| − | ====Chemotherapy====
| |
| − | '''3 Cycles'''
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| − | *[[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
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| − | *High Dose [[Methotrexate (MTX)]] 400 mg/kg (20 gram maximum) IV over 4 hours on day 1
| |
| − | *[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> 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
| |
| − | *[[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
| |
| − | *[[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
| |
| − | *[[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
| |
| − | *[[Filgrastim (Neupogen)]] 5 μg/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 μg/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'''
| |
| − | ===Consolidation===
| |
| − | ====Chemotherapy====
| |
| − | '''3 Cycles'''
| |
| − | *[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours given daily on Days 1 & 2
| |
| − | ** If corrected GFR is < 100 ml/min/1.73m<sup>2</sup>, 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
| |
| − | | |
| − | *[[Filgrastim (Neupogen)]] 5 μg/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:''' P.D. Aridgides, G. Kang, C. Mazewski, T.E. Merchant. Outcomes after Radiation Therapy for Very Young Children with High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG ACNS0334. Radiation Oncology 105, no. 1 (September 1, 2019)[https://doi.org/10.1016/j.ijrobp.2019.06.602 link to original article] NCT00336024
| |
| − | ==Head Start III Regimen D2==
| |
| − | ===Induction Cycles 1 & 3===
| |
| − | ====Chemotherapy====
| |
| − | *[[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
| |
| − | *[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> 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'''
| |
| − | ===Induction Cycles 2 & 4===
| |
| − | ====Chemotherapy====
| |
| − | *[[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 course'''
| |
| − | ===Induction Cycle 5===
| |
| − | ====Chemotherapy====
| |
| − | *[[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
| |
| − | *[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> 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'''
| |
| − | ===Myeloablative Chemotherapy with AuHCR===
| |
| − | *Patients with no evidence of disease (NED) after induction or second look surgery.
| |
| − | ====Chemotherapy====
| |
| − | *[[Carboplatin (Paraplatin)]] AUC of 7/day once daily on days 1 to 3
| |
| − | *[[Thiotepa (Thioplex)]] 300 mg/m<sup>2</sup> IV once daily on Days 1 to 3 immediately following [[Carboplatin (Paraplatin)]] administration
| |
| − | *[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> 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-Oncology 2020 Apr 18: 22(12);1862-1872 [https://doi.org/10.1093/neuonc/noaa102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32304218/ link to PubMed] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746930/ link to PMC article] NCT00392327 | |
| − | | |
| − | ==SJMB 96 High Risk==
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | '''2 Cycles'''
| |
| − | *[[Topotecan (Hycamtin)]] 5.5 mg/m<sup>2</sup> 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?)
| |
| − | *[[Filgrastim (Neupogen)]] 10 μg/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: | |
| − | **M<sub>0</sub> - M<sub>1</sub>: 36 Gy in 18 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
| |
| − | | |
| − | *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>
| |
| − | *6-week rest period following radiotherapy
| |
| − | '''~ 6 week duration'''
| |
| − | | |
| − | ====High Dose Chemotherapy with PBSC support====
| |
| − | '''4 Cycles'''
| |
| − | *[[Amifostine (Ethyol)]] 600 mg/m<sup>2</sup> 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/m<sup>2</sup> IV over 6 hours on day -4
| |
| − | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push per day on day -4
| |
| − | *[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV push 15 minutes prior to [[Cyclophosphamide (Cytoxan)]] infusion on days -3, -2
| |
| − | *[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV infusion over 1 hour on days -3, -2
| |
| − | *[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion on days -3, -2
| |
| − | *PBSC Infusion on day 0
| |
| − | *[[Filgrastim (Neupogen)]] 5 μg/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.
| |
| − | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push per day on day 6
| |
| − | '''28 Day Cycles'''
| |
| − | | |
| − | ===References===
| |
| − | #''' SJMB96:''' 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
| |
| − | ##''' 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] NCT00003211
| |
| − | | |
| − | ==SJMB 96 Average Risk==
| |
| − | ====PBSC Harvest====
| |
| − | *[[Filgrastim (Neupogen)]] 10 μg/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'''
| |
| − | | |
| − | ====High Dose Chemotherapy with PBSC support====
| |
| − | '''4 Cycles'''
| |
| − | *[[Amifostine (Ethyol)]] 600 mg/m<sup>2</sup> 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/m<sup>2</sup> IV over 6 hours on day -4
| |
| − | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push per day on day -4
| |
| − | *[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV push 15 minutes prior to [[Cyclophosphamide (Cytoxan)]] infusion on days -3, -2
| |
| − | *[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV infusion over 1 hour on days -3, -2
| |
| − | *[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion on days -3, -2
| |
| − | *PBSC Infusion on day 0
| |
| − | *[[Filgrastim (Neupogen)]] 5 μg/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.
| |
| − | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push per day on day 6
| |
| − | '''28 Day Cycles'''
| |
| − | | |
| − | ===References===
| |
| − | #''' SJMB96:''' 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
| |
| − | ##''' 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] NCT00003211
| |
| − | | |
| − | | |
| − | | |
| − | [[Category:Medulloblastoma regimens]]
| |
| − | [[Category:Disease-specific pages]]
| |
| − | [[Category:Pediatric neurologic neoplasms]]
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