Difference between revisions of "Medulloblastoma"
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=Upfront Therapy= | =Upfront Therapy= | ||
==COGACNS1221 Protocol== | ==COGACNS1221 Protocol== | ||
− | ===Induction Therapy (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin) === | + | ===Induction Therapy (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin)=== |
+ | Given for cycles 1, 2 & 3 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Vincristine (Oncovin)]] by the following criteria | *[[Vincristine (Oncovin)]] by the following criteria | ||
Line 255: | Line 256: | ||
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF | **ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF | ||
− | ''' | + | '''63 day cycle''' |
− | |||
===References=== | ===References=== |
Revision as of 12:11, 26 March 2022
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COG ACNS0331 Standard Dose CSRT/Reduced Volume Boost to Tumor Bed
- Ages 3+
- All patients must begin therapy within 31 days of surgery.
Chemoradiotherapy
XRT
- 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
- 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
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. link to original article NCT00085735
Maintenance Regimen A
Cycles 1, 2, 4, 5, 7, 8
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
- Pediatric Lomustine Dosing Chart
- Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Dose rounded down to the nearest 0.1 mg
- Can be given IV push over 1-minute or by infusion via minibag as per institution policy
6-week cycle
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. link to original article NCT00085735
Maintenance Regimen B
Cycles 3, 6, and 9
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV given over 1 hour on Days 1, 2
- Mesna (Mesnex) 360 mg/m2 IV over 15 to 30 minutes on Days 1, 2
- Dose 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
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8
- Dose rounded down to the nearest 0.1 mg
- Can be given IV push over 1-minute or by infusion via minibag as per institution policy
6-week course
References
- COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735
COG ACNS0331 Standard Dose CSRT/Standard Volume Boost
- Ages 3+
- All patients must begin therapy within 31 days of surgery.
Chemoradiotherapy
XRT
- 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
- 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
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. link to original article NCT00085735
Maintenance Regimen A
Cycles 1, 2, 4, 5, 7, 8
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
- Pediatric Lomustine Dosing Chart
- Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- Dose rounded down to the nearest 0.1 mg
- Can be given IV push over 1-minute or by infusion via minibag as per institution policy
6-week cycle
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. link to original article NCT00085735
Maintenance Regimen B
Cycles 3, 6, and 9
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV given over 1 hour on Days 1, 2
- Mesna (Mesnex) 360 mg/m2 IV over 15 to 30 minutes on Days 1, 2
- Dose given at least 15 minutes prior to or at the same time as Cyclophosphamide (Cytoxan) and repeated at 4 and 8 hours post Cyclophosphamide (Cytoxan)
- Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 8 hours after the end of the Cyclophosphamide (Cytoxan) infusion
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8
- Dose rounded down to the nearest 0.1 mg
- Can be given IV push over 1-minute or by infusion via minibag as per institution policy
6-week course
References
- COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. link to original article NCT00085735
COG ACNS0332 Regimen A
Chemoradiotherapy
XRT
- Craniospinal External beam radiotherapy 36 Gy in 20 daily fractions (Monday - Friday)
- Posterior Fossa Boost External beam radiotherapy 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)
- Round vincristine down to the nearest 0.1 mg
6-Week Course
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. 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. link to original article NCT00392327
Maintenance Cycle
Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8
- Round vincristine down to the nearest 0.1 mg
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 1 hour once on days 2, 3
- Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2
28-Day Course
References
- COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
- COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327
COG ACNS0332 Regimen B
Chemoradiotherapy
XRT
- Craniospinal External beam radiotherapy 36 Gy in 20 daily fractions (Monday - Friday)
- Posterior Fossa Boost External beam radiotherapy 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)
- Round vincristine down to the nearest 0.1 mg
- Administer prior to Carboplatin
- Carboplatin (Paraplatin) 35 mg/m2 IV over 15 minutes given daily 1 to 4 hours prior to radiation therapy (Total of 30 doses)
- Carboplatin (Paraplatin) first dose administered on the first day of radiation therapy
- Carboplatin (Paraplatin) should be HELD if radiation treatment is not given
- Since there are 31 fractions of radiation, No Carboplatin (Paraplatin) should be given prior to the final radiation fraction
6-Week Course
- COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
- COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327
Maintenance Cycle
Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8
- Round vincristine down to the nearest 0.1 mg
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 1 hour once on days 2, 3
- Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2
28-Day Course
References
- COG ACNS0332: Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. link to original article NCT00392327
- COG ACNS0332: Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. link to original article NCT00392327
COG ACNS0334 Regimen A
Induction
Chemotherapy
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
- Etoposide (Vepesid) 2.5 mg/kg (maximum concentration of Etoposide (Vepesid) is 0.4 mg/ml) IV over 1 hour once daily on Day 1, 2, 3
- Begin Etoposide (Vepesid) infusion 1 hour before the Cyclophosphamide (Cytoxan) or Cisplatin (Platinol) infusions
- Cyclophosphamide (Cytoxan) 60 mg/kg IV over 1 hour (Hour 1-2) on Days 1, 2 with hyperhydration and Mesna (Mesnex)
- Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
- 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
- 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)]
21 Day Course
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)link to original article NCT00336024
COG ACNS0334 Regimen B
Induction
Chemotherapy
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
- 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
- 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
21 Day Course
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)link to original article NCT00336024
Consolidation
Chemotherapy
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)link to original article NCT00336024
Upfront Therapy
COGACNS1221 Protocol
Induction Therapy (Vincristine, Cyclophosphamide, MTX, Etoposide, Carboplatin)
Given for cycles 1, 2 & 3
Chemotherapy
- Vincristine (Oncovin) by the following criteria
- Ages 0 to 6.99 months: 1 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
- Ages 7 to 12.99: 1.2 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
- Ages ≥13: 1.5 mg/m2 IV once per day on days 1, 15, & 29 (maximum dose of 2 mg)
- Can be given IV push over 1-minute or by infusion via minibag as per institution policy
- Cyclophosphamide (Cytoxan) by the following criteria
- Ages 0 to 6.99 months: 533 mg/m2 IV over 1 hour once per day on days 1 to 3
- Ages 7 to 12.99 months: 640 mg/m2 IV over 1 hour once per day on days 1 to 3
- Ages ≥13 months: 800 mg/m2 IV over 1 hour once per day on days 1 to 3
- Mesna (Mesnex) by the following criteria
- Ages 0 to 6.99 months: 533 mg/m2 IV over 1 hour once per day on days 1 to 3
- Ages 7 to 12.99 months: 640 mg/m2 IV over 1 hour once per day on days 1 to 3
- Ages ≥13 months: 800 mg/m2 IV over 1 hour once per day on days 1 to 3
- Mesna (Mesnex) Dose can be given in 5 divided doses by short IV infusion over 15 to 30 minutes starting 15 minutes before Cyclophosphamide (Cytoxan) with subsequent doses given at 3, 6, 9, & 12 hours after the start of Cyclophosphamide (Cytoxan)
- Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as Cyclophosphamide (Cytoxan) and finished no sooner than 12 hours after the end of the Cyclophosphamide (Cytoxan) infusion
- High Dose Methotrexate (MTX) 5000 mg/m2 IV over 24 hours on days 15 & 29
- Methotrexate (MTX) 500 mg/m2 IV infused over 30 minutes, then Methotrexate (MTX) 4500 mg/m2 given by continuous IV infusion over 23.5 hours
- Folinic acid (Leucovorin) 15 mg/m2 IV or PO given at 42, 48 & 54 hours after start of Methotrexate (MTX) infusion on days 17 & 31
- Folinic acid (Leucovorin) should be continued until serum Methotrexate (MTX) levels are less than 0.1 µM
- Can be given as an IV push over a minimum of 3 minutes or by short infusion over 15 to 120 minutes
- Etoposide (Vepesid) 150 mg/m2 IV over 60 to 120 minutes (maximum rate of 300 mg/m2/hr) once per day on days 43 to 45
- Administer Etoposide (Vepesid) prior to Carboplatin (Paraplatin)
- Carboplatin (Paraplatin) by the following criteria
- Ages 0 to 6.99 months: 133 mg/m2 IV over 1 hour once per day on days 43 to 45
- Ages 7 to 12.99 months: 160 mg/m2 IV over 1 hour once per day on days 43 to 45
- Ages ≥13 months: 200 mg/m2 IV over 1 hour once per day on days 43 to 45
- Filgrastim (Neupogen) 5 mcg/kg SC or IV daily for at least 7 days, or until ANC ≥ 750/μl, beginning on day 4 & 46
- ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF
63 day cycle
References
- COG ACNS1221: L. Lafay-Cousin, E. Bouffet, D. Strother, V. Rudneva, C. Hawkins, C. Eberhart, C. Horbinski, L. Heier, M. Souweidane, C. Williams-Hughes, A. Onar-Thomas, C. A. Billups, M. Fouladi, P. Northcott, G. Robinson, A. Gajjar. Phase II Study of Nonmetastatic Desmoplastic Medulloblastoma in Children Younger than 4 Years of Age: A Report of the Children's Oncology Group (ACNS1221). Journal of Clinical Oncology. 2019 Nov 38:3, 243-51. link to original article link to PMC article PubMed NCT02017964
Adjuvant therapy
Carboplatin, Cyclophosphamide, Etoposide, Methotrexate, Vincristine
back to top |
Regimen
Study | Evidence |
---|---|
Rutkowski et al. 2005 | Non-randomized |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin)
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Methotrexate (MTX)
- Vincristine (Oncovin)
References
- Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10;352(10):978-86. link to original article PubMed
Cisplatin, Lomustine, Vincristine
back to top |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Packer et al. 2006 (COG A9961) | 1996-2000 | Phase 3 (C) | Cisplatin, Cyclophosphamide, Vincristine | Did not meet primary endpoint of EFS |
Note: neither the cycle length nor the exact dosing instructions for vincristine are clear from the manuscript.
Preceding treatment
- Surgery, then radiotherapy
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 0
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 7, 14
8 cycles (see note)
References
- COG A9961: Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. link to original article contains partially verified protocol PubMed NCT00002875
Cyclophosphamide & Vincristine/Cisplatin & Etoposide
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Protocol
Study | Evidence |
---|---|
Duffner et al. 1993 | Non-randomized |
Total duration of treatment is 12 to 24 months.
Preceding treatment
- Surgical resection or biopsy
Chemotherapy, part 1
28-day cycle for 2 cycles, alternating with part 2
Chemotherapy, part 2
28-day cycle for 1 cycle, alternating with part 1
References
- Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. link to original article PubMed
VCP
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VCP: Vincristine, CCNU (Lomustine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zeltzer et al. 1999 (CCG-921) | 1986-1992 | Phase 3 (C) | 8-in-1 | Superior PFS |
Preceding treatment
- Surgery, then Vincristine & RT
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15
- Lomustine (CCNU) 100 mg/m2 IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
6-week cycle for 8 cycles
References
- CCG-921: Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999 Mar;17(3):832-45. link to original article contains verified protocol PubMed