Brain Cancer Treatment Regimens

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BRAIN CANCER TREATMENT REGIMENS

The selection, dosing, and administration of anticancer agents and the management of associated toxicities are complex. Drug dose modifications and schedule and initiation of supportive care interventions are often necessary because of expected toxicities and because of individual patient variability, prior treatment, and comorbidities. Thus, the optimal delivery of anticancer agents requires a healthcare delivery team experienced in the use of such agents and the management of associated toxicities in patients with cancer. The cancer treatment regimens below may include both FDA-approved and unapproved uses/regimens and are provided as references only to the latest treatment strategies. Clinicians must choose and verify treatment options based on the individual patient.

NOTE: GREY SHADED BOXES CONTAIN UPDATED REGIMENS.

REGIMEN

DOSING

Adult Low-Grade Infiltrative Supratentorial Astrocytoma/Oligodendroglioma

(Excluding Pilocytic Astrocytoma)

Adjuvant Treatment

Temozolomide (Temodar; TMZ)1–3

Temozolomide 75mg/m2 orally daily from the first day of radiotherapy until the last day of radiotherapy, but for no longer than 49 days followed by a 4 week break, then followed by

Days 1–5: Temozolomide 150mg/m2 orally for the first cycle then, barring any hematologic toxicities, temozolomide 200mg/m2 orally beginning with the second cycle.

Repeat cycle every 4 weeks for up to 6 cycles.

                                             or                                            

Days 1–49: Temozolomide 75mg/m2 orally.

Repeat cycle every 11 weeks.

Recurrent or Progressive Low-Grade Disease

Temozolomide1,3

Days 1–49: Temozolomide 75mg/m2 orally daily.

Repeat cycle every 11 weeks.

Cisplatin (Platinol) + etoposide (Toposar, VePesid, Etopophos; VP-16)1,4

Days 1–3: Cisplatin 25mg/m2/day IV + etoposide 100mg/m2/day IV.

Repeat cycle every 4 weeks for first 3 cycles,

then repeat every 5 weeks for next 3 cycles,

then repeat every 6 weeks for the last 3 cycles;

total 10 cycles over approximately 10–11 months

(total dose 750mg/m2 cisplatin and 3,000mg/m2 etoposide).

Carboplatin (Paraplatin)1,5

Carboplatin 560mg/m2 IV at 4-week intervals; continued until disease progression, unacceptable toxicity, or for 12 additional courses after achieving maximal response.

PCV (Procarbazine [Matulane] + lomustine [CeeNU; CCNU] + vincristine [Oncovin; Vincasar PFS])1,6

Day 1: Lomustine 110mg/m2 orally.

Days 8–21: Procarbazine 60mg/m2 orally once daily.

Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV.

Repeat every 6 weeks.

Anaplastic Gliomas

Adjuvant Treatment

Temozolomide1,7

Days 1–5: Temozolomide 200mg/m2/day orally.

Repeat cycle every 4 weeks until disease progression or for up to 24 cycles.

PCV with deferred RT1,8

Day 1: Lomustine 110mg/m2 orally.

Days 8–21: Procarbazine 60mg/m2 orally once daily.

Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV.

Repeat every 6 weeks.

Recurrent/Salvage Treatment

Temozolomide1,9

Temozolomide 50mg/m2 daily for up to 1 year or until disease progression.

Bevacizumab (Avastin) + irinotecan (Camptosar; CPT-11)1,10

Day 1: Bevacizumab 10mg/kg IV in combination with irinotecan 125mg/m2, or 340mg/m2 IV in patients receiving enzyme inducing antiepileptics.

Repeat once every 2 weeks.

Cyclophosphamide (Cytoxan)1,11

Days 1–2: Cyclophosphamide 750mg/m2 IV.

Repeat cycle every 4 weeks.

PCV1,6

Day 1: Lomustine 110mg/m2 orally.

Days 8–21: Procarbazine 60mg/m2 orally once daily.

Days 8 & 29: Vincristine 1.4mg/m2 (maximum 2mg) IV.

Repeat every 6 weeks.

Etoposide1,12

Etoposide 50mg daily.

Glioblastoma

Adjuvant treatment

Temozolomide1,2

Concurrent with radiotherapy

Temozolomide 75mg/m2/day orally.

Post-radiotherapy

Days 1–5: Temozolomide 150–200mg/m2 orally.

Repeat cycle every 4 weeks.

Recurrent/Salvage Treatment

Bevacizumab + irinotecan1,13

Initial therapy

Day 1: Bevacizumab 10mg/kg IV.

Repeat every 2 weeks until disease progression.

After tumor progression

Day 1: Bevacizumab 10mg/kg IV + irinotecan 125mg/m2, or

340mg/m2 IV in patients receiving enzyme inducing antiepileptics.

Repeat once every 2 weeks.

Cyclophosphamide1,11

Days 1–2: Cyclophosphamide 750mg/m2 IV.

Repeat cycle every 4 weeks.

Nitrosourea wafer (Gliadel [polifeprosan 20 with carmustine implant])1,14,15

Place up to 8 wafers in resection cavity.

PCV1,6

Day 1: Lomustine 110mg/m2 orally.

Days 8–21: Procarbazine 60mg/m2 orally once daily.

Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV.

Repeat every 6 weeks.

Bevacizumab1,16

Day 1: Bevacizumab 10mg/kg.

Repeat every 2 weeks.

Meningioma

Alpha-interferon (α-IFN)1,17

α-IFN 10 million Units/m2 SC every other day for 4 weeks.

Repeat cycle every 4 weeks.

Primary CNS Lymphoma

Primary Treatment

High-dose methotrexate (MTX) 8g/m2 combination therapy + deferred RT1,18

 

 

 

   

  

 

 Plus

Rituximab [Rituxan]1,19

 
 

                    OR                   

Rituximab + temozolomide1,20

Induction therapy

MTX 8g/m2 IV administered every 2 weeks until complete response achieved or max of 8 cycles reached.

Consolidation

MTX 8g/m2 IV administered every 2 weeks for 2 cycles.

Maintenance therapy

MTX 8g/m2 IV administered every 4 weeks for 11 cycles.

 

 

Plus

Rituximab

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

                                             or                                            

Rituximab + temozolomide

Induction therapy

Day 1: Rituximab 375mg/m2 IV, followed by

Days 1–5: Temozolomide 150–200mg/m2 orally daily, after rituximab infusion.

Repeat cycle every 4 weeks for 4 cycles.

Maintenance therapy

Days 1–5: Temozolomide 150–200mg/m2 orally daily.

Repeat cycle every 4 weeks for 8 cycles.

High-dose methotrexate (MTX) 3.5g/m2 combination therapy + RT

 

Plus

Cytarabine (Cytosar-U; ARA-C)1,21

 

 

 

                    OR                   

R-MPV (Rituximab + MTX + leucovorin + procarbazine + vincristine1,22,23

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                   OR                   

MPV (MTX + leucovorin + procarbazine + vincristine)1,21,24

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                    OR                   

Ifosfamide1,25

High-dose methotrexate (MTX) 3.5g/m2 combination therapy + RT.

 

 

Plus

Cytarabine

Day 1: MTX 3.5g/m2 IV, followed by

Days 2 and 3: Cytarabine 2g/m2 IV twice daily.

Repeat cycle every 3 weeks for 4 cycles and follow with whole-brain irradiation.

                                             or                                            

R-MPV

Day 1: Rituximab (Rituxan) 500mg/m2 IV.

Day 2: MTX 3.5g/m2 IV, followed by leucovorin 20–25mg every 6 hrs starting 24 hrs after MTX infusion for 72 hrs or until serum MTX level <1 x 10–8mg/dL. Increase leucovorin to 40mg every 4 hrs if MTX level >1 x 10–5mg/dL at

48 hours, or >1 x 10–8mg/dL at 72 hrs.

Day 2: Vincristine 1.4mg/m2 (max 2.8mg) IV.

Days 1–7: Procarbazine 100mg/m2 orally once daily of odd-numbered cycles only.

Use along with growth factor supplementation for 3–5 days starting

24 hrs after the last dose of procarbazine during odd-numbered cycles, and starting 96 hrs after MTX infusion or when MTX levels <1 x 10-8mg/dL during even-numbered cycles.

If positive CSF cytology: MTX 12mg intra-ommaya between days 5 and 12 of each cycle.

Repeat cycle every 2 weeks for 5 cycles.

If CR, begin whole-brain radiotherapy (WBRT) 3–5 weeks after R-MPV.

If PR, 2 more additional cycles of R-MPV.

If CR after 7 cycles of R-MPV, WBRT beginning 3–5 weeks after the completion of R-MPV.

If persistent disease after 7 cycles of R-MPV, WBRT beginning 3–5 weeks after the completion of R-MPV.

If stable disease or progressive disease after 5 cycles of R-MPV, WBRT beginning 3–5 weeks after the completion of R-MPV. 3 weeks after completion of WBRT, consolidation cytarabine 3g/m2/day (max 6g) IV for

2 days.

Use along with growth factor supplementation for 10 days starting 48 hrs after completion of cytarabine.

A second cycle of cytarabine given 1 month later.

                                             or                                            

MPV

Day 1: MTX 3.5g/m2 IV.

Day 2: Leucovorin 10mg every 6 hrs for 12 doses starting 24 hrs after MTX infusion.

Day 1: Vincristine 1.4mg/m2 (max 2.8mg) IV.

Days 1–7: Procarbazine 100mg/m2 orally once daily cycles 1, 3, and 5 only.

Repeat every 2 weeks for 5 cycles.

MTX 12mg intra-ommaya on alternate weeks after systemic MTX.

Leucovorin 10mg every 6 hrs for 8 doses starting 24 hrs after intra-ommaya MTX.

3–5 weeks after MPV, WBRT for patients <60 years.

3 weeks after WBRT, consolidation cytarabine 3g/m2/day IV for 2 days.

A second cycle of cytarabine given 1 month later.

                                             or                                            

Ifosfamide

Day 1: MTX 4gm/m2 IV, followed by leucovorin 20–25mg IV every 6 hrs starting 24 hrs after MTX for 72 hrs or until serum MTX level <1 x 10–8mg/dL. Increase leucovorin to 40mg every 4 hrs if MTX level >1 x 10–5mg/dL at

48 hours or >1 x 10–8mg/dL at 72 hrs.

Days 3–5: Ifosfamide 1.5gm/m2 IV + mesna 400mg IV before ifosfamide, then 4 hrs and 8 hrs after.

Recurrence or Progressive Disease

Consider high-dose chemotherapy with autologous stem cell reinfusion in patients who achieve a complete response with conventional doses of salvage chemotherapy or have no residual disease after re-resection.

High-dose MTX

Retreat (see regimen above).

Temozolomide or topotecan

(Hycamtin)1,26

Topotecan

Days 1–5: Topotecan 1.5mg/m2.

Repeat every 3 weeks.

Rituximab + temozolomide1,27

Induction therapy

Day 1: Rituximab 375mg/m2 IV, plus

Days 1–5: Temozolomide 150–200mg/m2 orally daily, administered after rituximab infusion.

Repeat cycle every 4 weeks for 4 cycles.

Maintenance therapy

Days 1–5: Temozolomide 150–200mg/m2 orally daily, administered after rituximab infusion.

Repeat cycle every 4 weeks for 8 cycles.

Adult Medulloblastoma and Supratentorial Primitive Neuroectodermal Tumor (PNET)

Adjuvant Treatment

Vincristine + cisplatin + lomustine1,28

During craniospinal radiotherapy (RT)

Day 1: Lomustine 75mg/m2 orally.

Day 2: Cisplatin 75mg/m2 IV.

Days 2, 8 and 15: Vincristine 1.5mg/m2 IV bolus, max 2mg bolus; up to max 8 doses.

*Data supporting the use of VCR have been found in pediatric trials only. Omission of VCR during RT or dose modification may be required for adults because they do not tolerate this regimen as well as children.

Vincristine + cisplatin + cyclophosphamide1,28

Day 1: Cisplatin 75mg/m2 IV.

Days 2, 8 and 15: Vincristine 1.5mg/m2 IV bolus, max 2mg bolus.

Days 22, 23: Cyclophosphamide 1,000mg/m2 IV.

*Data supporting the use of VCR have been found in pediatric trials only. Omission of VCR during RT or dose modification may be required for adults because they do not tolerate this regimen as well as children.

Recurrence/Salvage Treatment (No Prior Chemotherapy)

High-dose cyclophosphamide ± etoposide1

                                             

Carboplatin + etoposide + cyclophosphamide1         

                                             

Cisplatin + etoposide + cyclophosphamide1

Consider high-dose chemotherapy with autologous stem cell reinfusion in patients who achieve a complete response with conventional doses of salvage chemotherapy or have no residual disease after re-resection.

Recurrence/Salvage Treatment (Prior Chemotherapy)

Consider high-dose chemotherapy with autologous stem cell reinfusion in patients who achieve a complete response with conventional doses of salvage chemotherapy or have no residual disease after re-resection.

High-dose cyclophosphamide ± etoposide1

Plus

Etoposide1,29,30

 

 

 

 

Days 1–21: Etoposide 50mg daily.

Repeat every 4 weeks.

Temozolomide1,31

Days 1–5: Temozolomide 180mg/m2/day (patients with prior craniospinal irradiation [CSI]) or 200mg/m2/day (patients with no prior CSI).

Repeat every cycle every 4 weeks for up to 11 cycles.

References

  1. NCCN Clinical Practice Guidelines in Oncology™. Central Nervous System Cancers. v 1.2012. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed May 4, 2012.

  2. Stupp R, Mason WP, van den Bent MJ, et al. European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–996.

  3. Kesari S, Schiff D, Drappatz J, et al. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res. 2009;15:330–337.

  4. Massimino M, Spreafico F, Riva D, et al. A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma. J Neurooncol. 2010;100:65–71.

  5. Moghrabi A, Friedman HS, Ashley DM, et al. Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas. Neurosurg Focus. 1998;4:e3.

  6. Triebels VH, Taphoorn MJ, Brandes AA, et al. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas. Neurology. 2004;63:904–906.

  7. Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol. 2006 Sep;79(2):153–157.

  8. Wick W, Hartmann C, Engel C, et al. NOA-04 randomized phased III trails of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolamide. J Clin Oncol. 2009;27:5874–5880.

  9. Perry JR, Bélanger K, Mason WP, et al. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010;28:2051–2057.

10. Taillibert S, Vincent LA, Granger B, et al. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009;72:1601–1606.

11. Chamberlain MC, Tsao-Wei DD. Salvage chemotherapy with cyclophosphamide for recurrent, temozolomide-refractory glioblastoma multiforme. Cancer. 2004;100:1213–1220.

12. Fulton D, Urtasun R, Forsyth P. Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol. 1996;27:149–155.

13. Kreisl TN, Kim L, Moore K, et al. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009;27:740–745.

14. Brem H, Piantadosi S, Burger PC, et al. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet. 1995;345:1008–1012.

15. Glidadel® Wafer [package insert]. Woodcliff Lake, NJ: Eisai, Inc.; 2010.

16. Cloughesy TF, Prados MD, Wen PY. A phase II randomized non-comparative clinical trial of the effect of bevacizumab alone or in combination with irinotecan on 6 month progression free survival (PFS6) in recurrent treatment-refractory glioblastoma (GBM) [abstract]. J Clin Oncol. 2008;26(suppl 15):2010b.

17. Chamberlain MC, Glantz MJ. Interferon-alpha for recurrent World Health Organization grade 1 intracranial meningiomas. Cancer. 2008;113:2146–2151.

18. Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96–07. J Clin Oncol. 2003;21:1044–1049.

19. Chamberlain MC, Johnson SK. High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro Oncol. 2010;12: 736–744.

20. Wieduwilt MJ, Valles F, Issa S, et al. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012;18:1146–1155.

21. Ferreri AJ, Reni M, Foppoli M, et al; International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009;374:1512–1520.

22. Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007;25:4730–4735.

23. Gavrilovic IT, Hormigo A, Yahalom J, et al. Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2006;24:4570–4574.

24. Abrey LE, Yahalom J, DeAngelis LM, et al. Treatment of primary CNS lymphoma: the next step. J Clin Oncol. 2000;18: 3144–3150.

25. Thiel E, Korfel, Martus P, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncology. 2010;11;1036–1047.

26. Voloschin A, Betensky R, Wen PY, et al. Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma. Neurooncology. 2008;86:211–215.

27. Wong ET, Tishler R, Barron L, Wu JK. Immunochemotherapy with rituximab and temozolomide for central nervous system lymphomas. Cancer. 2004;101:139–145.

28. Packer RJ, Gajjar A, Vezina G, et al. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006;24:4202–4208.

29. Ashley DM, Meier L, Kerby T, et al. Response of recurrent medulloblastoma to low-dose oral etoposide. J Clin Oncol. 1996;14:1922–1927.

30. Chamberlain MC, Kormanik PA. Chronic oral VP-16 for recurrent medulloblastoma. Pediatr Neurol. 1997;17: 230–234.

31. Nicholson HS, Kretschmar CS, Krailo M, et al. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007;110:1542–1550.


Central Nervous System Cancer Drug Monographs

Brain Cancer



Afinitor
Avastin Bicnu Ceenu
Gliadel Temodar Vincasar PFS

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.
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