Brain Cancer Treatment Regimens

Combination PCV (lomustine + procarbazine + vincristine) (Category 1)2

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.

Temozolomide3–5

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

Repeat cycle every 11 weeks (7 weeks on/4 weeks off) for 6 cycles.

OR

For children/adolescents: Temozolomide monthly 5-day courses at doses of 200mg/m2/day (patients with no prior craniospinal irradiation [CSI]) or 180mg/m2/day (prior CSI).

OR

Days 1–21: Temozolomide 75mg/m2/day orally.

Repeat cycle every 28 days.

Temozolomide3,6a

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

Repeat cycle every 11 weeks (7 weeks on/4 weeks off) for 6 cycles.

OR

Days 1–5: Temozolomide 150mg/m2 to 200mg/m2; when patients progress during conventional temozolomide treatment, change temozolomide to a 50mg/m2 daily regimen.

Repeat cycle every 28 days.

Combination PCV regimens (lomustine + procarbazine + vincristine)7

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.

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 IV

Days 1–3: Teniposide 50mg/m2 IV.

Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

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

Platinum-based regimen: Cisplatin10

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).

Lomustine11

Lomustine 130mg/m2 orally every 6 weeks.

Carmustine12

Carmustine 150–200mg/m2 IV as a single dose or divided over 2 days given every 6 weeks OR 75–100mg/m2/day IV for 2 days every 6 weeks.

Temozolomide13,14

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 RT13

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.

Concurrent temozolomide (with RT)15

2 Gy given 5 days/week for 6 weeks plus continuous daily oral temozolomide (75mg/m2/day, 7 days per week from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant temozolomide 150–200mg/m2/day for 5 days.

Repeat cycle every 28 days.

Temozolomide4,6,16

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

OR

For children/adolescents: Temozolomide monthly 5-day courses at doses of 200mg/m2/day (patients with no prior CSI) or 180mg/m2/day (prior CSI).

OR

Days 1–5: Temozolomide 150mg/m2 to 200mg/m2 5 days of each 28-day cycle; when patients progress during conventional temozolomide treatment, change temozolomide to a 50mg/m2 daily regimen.

OR

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

Repeat cycle every 28 days.

Lomustine or carmustine11,12,17

Day 1: Lomustine 100–130mg/m2/day orally.

Repeat cycle every 6 weeks.

OR

Carmustine 150–200mg/m2 IV as a single dose or divided over 2 days given every 6 weeks OR 75–100mg/m2/day IV for 2 days every 6 weeks.

Combination PCV regimens (lomustine + procarbazine + vincristine)7

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.

Bevacizumab18–20b

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 14 days.

Bevacizumab + irinotecan21,22c

Day 1: Bevacizumab 10mg/kg IV plus irinotecan 125mg/m2 IV.

Repeat cycle every 2 weeks.

OR

Bevacizumab 10mg/mg2 IV plus irinotecan 340mg/m2 IV in patients receiving enzyme-inducing antiepileptic drugs (EIAED).

Repeat cycle every 14 days.

Bevacizumab + nitrosurea23

Days 1 and 15: Bevacizumab 10mg/kg IV

Days 1 and 8: Fotemustine 75mg/m2 IV

Followed after a 3-week interval by a maintenance phase of bevacizumab 10mg/kg IV plus fotemustine 75mg/m2 IV.

Repeat cycle every 3 weeks.

Bevacizumab + carboplatin (Category 2B)24,25

Day 1: Bevacizumab 10mg/kg IV plus carboplatin AUC 4–6mg •min/mL, depending on the patient’s prior treatment history and bone marrow reserves; cycle 2 doses of carboplatin (every 28 days) and 3 doses of bevacizumab (every 14 days) and lasted 6 weeks.

Irinotecan26,27

Day 1: Irinotecan 350mg/m2 IV to patients on non-enzyme-inducing antiepileptic drugs (NEIAED) or 600mg/m2 to patients on EIAED.

Repeat cycle every 21 days.

OR

Day 1: Irinotecan 350mg/m2 IV.

Repeat cycle every 21 days.

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 IV

Days 1–3: Teniposide 50mg/m2 IV.

Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

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

Platinum-based regimen: Cisplatin10

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).

Cyclophosphamide (Category 2B)28,29

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

Repeat cycle every 28 days.

Etoposide30

Etoposide 50mg/day IV given until the neutrophil count dropped to < 1.0 × 109/L or the platelets fell to < 75 × 109/L and resumed when the counts rose to normal levels.

Radiotherapy + PCV for 1p19q co-deleted (Category 1)31

59.6 4 Gy of RT, followed by 6 cycles of standard PCV:

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.

Concurrent temozolomide (with RT)15

2 Gy given 5 days/week for 6 weeks plus continuous daily oral temozolomide (75mg/m2/day, 7 days per week from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant temozolomide 150–200mg/m2/day for 5 days.

Repeat cycle every 28 days.

Post-RT temozolomide32

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

Repeat cycle every 28 days.

Temozolomide + standard RT33

Days 1–5: Temozolomide 200mg/m2, orally plus:

Standard RT: 60.0 Gy administered in 2.0 Gy fractions over 6 weeks.

Bevacizumab34–36b

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 14 days.

Bevacizumab + irinotecan22,34–36c

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 14 days.

After tumor progression, immediately treat with bevacizumab 10mg/kg IV plus irinotecan 340mg/m2 or 125mg/m2 IV every 14 days, depending on use of EIAEDs.

Bevacizumab + nitrosurea23c

Days 1 and 15: Bevacizumab 10mg/kg IV

Days 1 and 8: Fotemustine 75mg/m2 IV

Followed after a 3-week interval by a maintenance phase of bevacizumab 10mg/kg IV plus fotemustine 75mg/m2 IV.

Repeat cycle every 3 weeks.

Bevacizumab + carboplatin (Category 2B)24,25c

Day 1: Bevacizumab 10mg/kg IV plus carboplatin AUC 4–6mg • min/mL, depending on the patient’s prior treatment history and bone marrow reserves; cycle 2 doses of carboplatin (every 28 days) and 3 doses of bevacizumab (every 14 days) for 6 weeks.

Temozolomide6,32,37

Days 1–5: Temozolomide 150mg/m2 to 200mg/m2; when patients progress during conventional temozolomide treatment, change temozolomide to a 50mg/m2 daily regimen.

Repeat cycle every 28 days.

OR

2 Gy given 5 days/ week for 6 weeks plus continuous daily oral temozolomide (75mg/m2/day, 7 days per week from the first to the last day of radiotherapy), followed by 6 cycles of adjuvant temozolomide 150–200mg/m2/day for 5 days.

Repeat cycle every 28 days.

OR

Chemotherapy-naive patients:

Days 1–5: Temozolomide 200mg/m2/day.

Chemotherapy-experienced patients:

Days 1–5: Temozolomide 150mg/m2/day, increasing to 200mg/m2/day in the absence of grade 3/4 toxicity.

Repeat cycle every 28 days.

Lomustine or carmustine11,12,17

Day 1: Lomustine 100–130mg/m2/day orally.

Repeat cycle every 6 weeks.

OR

Carmustine 150–200mg/m2 IV as a single dose or divided over 2 days given every 6 weeks OR 75–100mg/m2/day IV for 2 days every 6 weeks.

Combination PCV regimens (lomustine + procarbazine + vincristine)7

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.

Cyclophosphamide (Category 2B)28

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

Repeat cycle every 28 days.

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2 IV

Days 1–3: Teniposide 50mg/m2 IV.

Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

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

Platinum-based regimen: Cisplatin10

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).

Platinum-based regimen: Carboplatin8

Day 1: Carboplatin 350mg/m2

Days 1–3: Teniposide 50mg/m2.

Repeat cycle every 4 weeks.

Platinum-based regimen: Carboplatin9

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

Platinum-based regimen: Cisplatin10

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).

Etoposide30

Etoposide 50mg/day given until the neutrophil count dropped to <1.0 × 109/L or the platelets fell to <75 × 109/L and resumed when the counts rose to normal levels.

Bevacizumab34–37b

Day 1: Bevacizumab 10mg/kg IV.

Repeat cycle every 14 days.

Temozolomide3–5

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

Repeat cycle every 11 weeks (7 weeks on/4 weeks off) for 6 cycles.

OR

Days 1–21: Temozolomide 75mg/m2/day orally.

Repeat cycle every 28 days.

Vincristine + cisplatin + lomustine38

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.

Vincristine + cisplatin + cyclophosphamide39

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.

High dose cyclophosphamide ± etoposide

Carboplatin + etoposide + cyclophosphamide

Cisplatin + etoposide + cyclophosphamide

High dose cyclophosphamide ± etoposide

Temozolomide3

Temozolomide 75mg/m2 orally in 11-week cycles of 7 weeks on followed by 4 weeks off.

Oral etoposide40,41

Days 1–21: Etoposide 50mg orally daily.

Repeat cycle every 4 weeks.

High dose methotrexate + chemotherapy42–44

High dose methotrexate combined with the following plus radiation therapy:

Weeks 1, 3, 5, 7, and 9: MTX 2.5g/m2 + vincristine 1.4mg/m2 with a cap of 2.8mg (2m2)

Weeks 1, 5, and 9: Procarbazine 100mg/m2/day orally for 7 days

Weeks, 2, 4, 6, 8, and 10: Methotrexate 12mg intraventicularly

Weeks 1, 3, 5, 7, and 9: Leucovorin 20mg every 6 hours orally for 12 doses

Weeks, 2, 4, 6, 8, and 10: Leucovorin 10mg orally twice daily for 8 doses

Weeks 11–15: Whole-brain RT in 1.80-Gy fractions for a total dose of 45 Gy

Weeks 16 and 19: Cytarabine 3g/m2/day IV for 2 days.

Repeat for 5 cycles.

OR

Day 1: MTX 3.5g/m2

Days 2–3: Cytarabine 2g/m2 IV twice a day.

OR

Day 1: MTX 4gm/m2 IV, followed by leucovorin 20–25mg IV every 6 hours starting 24 hours after MTX for 72 hours or until serum MTX level <1 × 10–8mg/dL. Increase leucovorin to 40mg every 4 hours if MTX level >1 × 10–5mg/dL at 48 hours or >1 × 10–8mg/dL at 72 hours.

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

High dose methotrexate (MTX 2.5–4.0g/m2) + chemotherapy ± monoclonal antibody45

Day 1: Rituximab 500mg/m2 IV

Day 2: MTX 3.5g/m2 IV plus vincristine 1.4mg/m2

Procarbazine 100mg/m2/day was administered for 7 days with odd-numbered cycles.

High dose methotrexate (MTX 8.0g/m2) + chemotherapy ± monoclonal antibody46–47

High dose methotrexate combined with the following plus radiation therapy deferred radiation therapy:

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

Day 1: Rituximab 375mg/m2 IV.

Repeat cycle every 4 weeks for 4 cycles.

OR

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.

Consider urgent glucarpidase (carboypeptidase G2) for prolonged MTX clearance due to MTX-induced renal toxicity48

Glucarpidase, one 50U/kg dose IV, 2 doses 24 hours apart, or 3 doses every 4 hours; thymidine 8 g/m2/day IV administered as continuous IV infusion for ≥48 hours after the last dose of glucarpidase; leucovorin 1g/m2 IV every 6 hours before administration of glucarpidase and at a dose of 250mg/m2 IV every 6 hours for 48 hours after administration of the last dose of glucarpidase.

Re-treat with high-dose methotrexate46

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.

Rituximab ± temozolomide49

Induction therapy

Day 1: Rituximab 375mg/m2 IV, ±

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.

Topotecan50

Days 1–5: Topotecan 1.5mg/m2 IV.

Repeat cycle every 21 days.

High-dose cytarabine51

Cytarabine 3g/m2 IV.

Dexamethasone + high-dose cytarabine + cisplatin52

Day 1: Cisplatin 100mg/m2 continuous IV infusion over 24 hours, followed by 2 pulses each of cytarabine at a dose of 2g/m2 given 12 hours apart.

Days 1–4: Dexamethasone 40mg PO or IV.

Repeat cycle every 3–4 weeks for 6–10 courses.

Pemetrexed53

Pemetrexed 900mg/m2 IV every 21 days for 6 weeks.

Interferon-alfa (Category 2B)54

α-IFN 106 units/m2 SC every other day for 4 weeks.

Repeat cycle every 4 weeks.

Somatostatin analog55

Sandostatin LAR Depot 10–30mg IM every 4 weeks.

Sunitinib (Category 2B)56

Days 1–28: Sunitinib 50mg orally daily.

Repeat cycle every 42 days.

Carmustine wafer57

8 wafers (7.7mg) for a total of 61.6mg implanted intracranially.

High-dose methotrexate (MTX; breast and lymphoma)58,59

Breast: MTX 3.5g/m2 IV.

Lymphoma: Treatment based on weekly high-dose MTX 3.5g/m2 and weekly intra-CSF cytarabine; oral procarbazine 100mg/m2 days 2–15 was added to patients whose bone marrow reserve could tolerate this drug.

Capecitabine ± lapatinib, cisplatin, etoposide60–68

Days 1–14: lapatinib 1,250mg orally plus capecitabine 1,000mg/m2 orally twice per day.

Repeat cycle every 21 days.

OR

Days 1–14: Capecitabine 2,000mg/m2/day in 2 divided doses for 14 days, followed by a 7-day rest and lapatinib 1,250mg once daily continuously.

OR

Day 1: Cisplatin 100mg/m2 IV

Days 4, 6, and 8: Etoposide 100mg/m2.

Repeat cycle every 21 days.

OR

Day 1: Cisplatin 100mg/m2 IV

Days 1, 3, and 5 OR Days 4, 6, and 8: Etoposide 100mg/m2 IV.

Repeat cycle every 21 days.

OR (breast)

Capecitabine orally starting at a dose of 1,800mg/m2/day (up to 2,000mg/m2/day) in 2 divided doses, and temozolomide given orally once daily at a starting dose of 75mg/m2/day. Concomitant daily doses given on days 1–5 and days 8–12, with cycles repeated every 21 days until disease progression.

OR (breast)

Days 1–14: Capecitabine 2,000mg/m2/day orally once daily.

Repeat cycle every 21 days.

OR (breast)

Days 1–21: Capecitabine 2,400mg/m2/day orally once daily.

Repeat cycle every 28 days.

Ipilimumab (melanoma)69

Day 1: Ipilimumab 10mg/kg IV.

Repeat cycle every 21 days for a maximum 4 cycles.

Individuals who were clinically stable at week 24 were eligible to receive ipilimumab 10mg/kg every 12 weeks.

BRAF inhibitors (melanoma): Dabrafenib70

Dabrafenib 150mg orally twice daily.

BRAF inhibitors (melanoma): Vemurafenib71

Vemurafenib 960mg orally twice daily.

Topotecan (small cell lung)50

Days 1–5: Topotecan 1.5mg/m2 IV over 30 minutes.

Repeat cycle every 21 days.

Intra-CSF chemotherapy: Liposomal (slow-release) cytarabine (lymphoma/leukemias)72,73

Induction

Liposomal cytarabine 50mg intrathecally once every 14 days for 2 doses.

Maintenance

Liposomal cytarabine 50mg every 14 days for 2 doses, followed by 50mg every 28 days for 2 doses.

OR

Induction

Liposomal cytarabine 50mg intraventricularly every 14 days for 3 doses plus rituximab 25mg intraventricularly twice per week for 8 doses.

Maintenance

Liposomal cytarabine 50mg intraventricularly once weekly plus rituximab 25mg intraventricularly twice weekly for 4 weeks.

Repeat cycle every 4 weeks until disease progression

Intra-CSF chemotherapy: topotecan74

Topotecan 400 μg intraventrically twice weekly for 6 weeks.

Intra-CSF chemotherapy: etoposide75

Induction

Days 1–5: Etoposide 0.5mg/day intra-CSF every other week for 8 weeks.

Maintenance

Days 1–5: Etoposide 0.5mg/day every 4 weeks.

Intra-CSF chemotherapy: trastuzumab76

Cumulative dose of intrathecal trastuzumab given in clinical studies was 1,040mg (SD 697.9, median 1,215, range 55–1,675)

Intra-CSF chemotherapy: Interferon-alfa (category 2B)77

IFN-α 1 × 106 IU subcutaneously every other day 3 times per week for 4 weeks by induction.

High-dose methotrexate for lymphoma and breast58

Breast: MTX 3.5g/m2 IV.

Erlotinib (Category 2B)78

Weekly pulse erlotinib for EGFR exon 19 or exon 21 L858R mutation non-small cell lung cancer; trial demonstrates that a new schedule of erlotnib administration may overcome acquired resistance to erlotinib. Pulsatile high-dose erlotinib was found to be effective against brain metastases in patients who had progressed while on treatment with standard-dose erlotinib.

Pulsatile high-dose erlotinib 1,500mg (median dose with range of 900–1,500mg) once weekly.

a For patients not previously treated

b Patients who have good performance status but evidence of radiographic progression may benefit from continuation of bevacizumab to prevent rapid neurologic deterioration

c Bevacizumab + chemotherapy can be considered for patients who have failed monotherapy with bevacizumab

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