BRAIN CANCER TREATMENT REGIMENS (Part 1 of 5)

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
Temozolomide 1,3 Days 1–49: Temozolomide 75mg/m2 orally daily.
Repeat cycle every 11 weeks.
Cisplatin (Platinol) + etoposide Days 1–3: Cisplatin 25mg/m2/day IV + etoposide 100mg/m2/day IV.
(Toposar, VePesid, Etopophos; Repeat cycle every 4 weeks for first 3 cycles,
VP-16) 1,4 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] + Day 1: Lomustine 110mg/m2 orally.
lomustine [CeeNU; CCNU] + Days 8–21: Procarbazine 60mg/m2 orally once daily.
vincristine [Oncovin; Vincasar Days 8 and 29: Vincristine 1.4mg/m2 (maximum 2mg) IV.
PFS])1,6 Repeat every 6 weeks.
Anaplastic Gliomas
Adjuvant Treatment
Temozolomide 1,7 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
Temozolomide 1,9 Temozolomide 50mg/m2 daily for up to 1 year or until disease progression.
Bevacizumab (Avastin) + Day 1: Bevacizumab 10mg/kg IV in combination with irinotecan 125mg/m2, OR
irinotecan (Camptosar; 340mg/m2 IV in patients receiving enzyme inducing antiepileptics.
CPT-11) 1,10 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.
continued
 BRAIN CANCER TREATMENT REGIMENS (Part 2 of 5)
REGIMEN
Glioblastoma
Adjuvant treatment
Temozolomide 1,2
Recurrent/Salvage Treatment
Bevacizumab + irinotecan 1,13
Cyclophosphamide 1,11
Nitrosourea wafer (Gliadel
[polifeprosan 20 with carmustine
1,14,15
implant])
PCV1,6
Bevacizumab1,16
Meningioma
Alpha-interferon (α-IFN) 1,17
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
DOSING
Concurrent with radiotherapy
Temozolomide 75mg/m2/day orally.
Post-radiotherapy
Days 1–5: Temozolomide 150–200mg/m2 orally.
Repeat cycle every 4 weeks.
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.
Days 1–2: Cyclophosphamide 750mg/m2 IV.
Repeat cycle every 4 weeks.
Place up to 8 wafers in resection cavity.
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.
Day 1: Bevacizumab 10mg/kg.
Repeat every 2 weeks.
α-IFN 10 million Units/m2 SC every other day for 4 weeks.
Repeat cycle every 4 weeks.
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.
continued
 BRAIN CANCER TREATMENT REGIMENS (Part 3 of 5)
REGIMEN
Primary CNS Lymphoma (continued)
Primary Treatment
High-dose methotrexate (MTX)
≥3.5g/m2 combination therapy
+ RT
PLUS
Cytarabine (Cytosar-U; ARA-C)1,21 Cytarabine
OR
R-MPV (Rituximab + MTX +
leucovorin + procarbazine +
vincristine1,22,23
OR
MPV (MTX + leucovorin +
procarbazine + vincristine)1,21,24
OR
Ifosfamide1,25
DOSING
High-dose methotrexate (MTX) ≥3.5g/m2 combination therapy + RT.
PLUS
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
2
Day 1: Rituximab (Rituxan) 500mg/m 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
2
Day 1: MTX 4gm/m 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.
continued
 BRAIN CANCER TREATMENT REGIMENS (Part 4 of 5)
REGIMEN DOSING
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 on previous page).
Temozolomide or topotecan Topotecan
(Hycamtin) 1,26 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 + During craniospinal radiotherapy (RT)
lomustine1,28 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 + Day 1: Cisplatin 75mg/m2 IV.
cyclophosphamide 1,28 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 ± Consider high-dose chemotherapy with autologous stem cell reinfusion in
etoposide 1 patients who achieve a complete response with conventional doses of salvage
Carboplatin + etoposide + chemotherapy or have no residual disease after re-resection.
cyclophosphamide 1
Cisplatin + etoposide +
cyclophosphamide 1
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 ±
etoposide 1
PLUS
Etoposide1,29,30 Days 1–21: Etoposide 50mg daily.
Repeat every 4 weeks.
Temozolomide 1,31 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.
continued
 BRAIN CANCER TREATMENT REGIMENS (Part 5 of 5)
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 Radiother-
apy Groups; National Cancer Institute of Canada Clinical Trials
Group. Radiotherapy plus concomitant and adjuvant temozo-
lomide 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 immuno-
chemotherapy 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.
(Revised 05/2012)
© 2012 Haymarket Media, Inc.