Difference between revisions of "Glioblastoma"
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===References=== | ===References=== | ||
− | #Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G, Muller P, Morawetz R, Schold SC; | + | #Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G, Muller P, Morawetz R, Schold SC; Polymer-Brain Tumor Treatment Group. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet. 1995 Apr 22;345(8956):1008-12. [https://www.thelancet.com/journals/lancet/article/PIIS0140673695907556/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/7723496 PubMed] |
#Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, Whittle IR, Jääskeläinen J, Ram Z. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003 Apr;5(2):79-88. [https://academic.oup.com/neuro-oncology/article/5/2/79/1070081 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920672/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/12672279 PubMed] | #Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, Whittle IR, Jääskeläinen J, Ram Z. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003 Apr;5(2):79-88. [https://academic.oup.com/neuro-oncology/article/5/2/79/1070081 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920672/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/12672279 PubMed] | ||
#'''PRECISE:''' Kunwar S, Chang S, Westphal M, Vogelbaum M, Sampson J, Barnett G, Shaffrey M, Ram Z, Piepmeier J, Prados M, Croteau D, Pedain C, Leland P, Husain SR, Joshi BH, Puri RK; PRECISE Study Group. Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol. 2010 Aug;12(8):871-81. Epub 2010 Feb 4. [https://academic.oup.com/neuro-oncology/article/12/8/871/1073747 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940677/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20511192 PubMed] | #'''PRECISE:''' Kunwar S, Chang S, Westphal M, Vogelbaum M, Sampson J, Barnett G, Shaffrey M, Ram Z, Piepmeier J, Prados M, Croteau D, Pedain C, Leland P, Husain SR, Joshi BH, Puri RK; PRECISE Study Group. Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol. 2010 Aug;12(8):871-81. Epub 2010 Feb 4. [https://academic.oup.com/neuro-oncology/article/12/8/871/1073747 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940677/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20511192 PubMed] |
Revision as of 13:29, 15 March 2020
Section editor | |
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Seema Nagpal, MD Stanford University Palo Alto, CA |
27 regimens on this page
43 variants on this page
|
Guidelines
ASCO
- 2016: Radiation therapy for glioblastoma: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the American Society for Radiation Oncology Guideline PubMed
EANO
- 2017: European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma PubMed
- 2014: EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma PubMed
ESMO
- 2014: Stupp et al. High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Adjuvant therapy, standard patients
Bevacizumab & RT
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Bevacizumab & RT: Bevacizumab & Radiation Therapy
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Herrlinger et al. 2016 (GLARIUS) | Randomized Phase II (E-switch-ooc) | Temozolomide & RT, then Temozolomide | Superior PFS-6 |
To be completed
Preceding treatment
Chemotherapy
Radiotherapy
Subsequent treatment
References
- GLARIUS: Herrlinger U, Schäfer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tüttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: the randomized GLARIUS trial. J Clin Oncol. 2016 May 10;34(14):1611-9. Epub 2016 Mar 14. link to original article PubMed
Carmustine & RT
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BCNU & RT: BCNU (Carmustine) & Radiation Therapy
Regimen variant #1, concurrent
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Eyre et al. 1986 (SWOG S7703) | Phase III (E-switch-ic) | 1. DTIC & RT | Not reported |
2. Procarbazine & RT | Superior ORR | ||
Dinapoli et al. 1993 | Phase III (C) | PCNU & RT | Did not meet primary endpoints of TTP50%/OS50% |
Buckner et al. 2001 | Phase III (C) | BCNU, IFN alfa, RT | Did not meet endpoint of OS50% |
Grossman et al. 2003 (ECOG E2394) | Phase III (C) | BCNU & Cisplatin, then RT | Did not meet primary endpoint of OS |
Buckner et al. 2006 (NCCTG 93-72-52/SWOG S9503) | Phase III (C) | BCNU, Cisplatin, RT | Did not meet primary endpoint of OS50% |
Blumenthal et al. 2014 (SWOG S0001) | Phase III (C) | BCNU, O⁶-benzylguanine, RT | Did not meet primary endpoint of OS |
Ali et al. 2018 (RTOG 9006) | Phase III (C) | BCNU & RT; hyperfractionated | Did not meet primary endpoint of OS |
Preceding treatment
Chemotherapy
Radiotherapy
Regimen variant #2, sequential
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Shapiro et al. 1989 (BTCG 8001) | Phase III (C) | 1. Carmustine, Procarbazine, RT | Did not meet primary endpoint of OS |
2. Carmustine & Hydrea/Procarbazine & VM-26 & RT | Did not meet primary endpoint of OS |
Preceding treatment
Radiotherapy
- External beam radiotherapy starting within 3 weeks after surgical resection, with ONE of the following:
- Whole brain: 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
- Whole brain & cone down: 172 cGy (rads) fractions x 25 fractions, given over 5 weeks for a total dose of 4300 cGy (4300 rads), then coned-down boost of 172 cGy (rads) fractions x 10 fractions, given over 2 weeks for a dose of 1720 cGy (rads), and a total cumulative dose of 6020 cGy (rads)
2- to 7-week course, followed by:
Chemotherapy
- Carmustine (BCNU) 80 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 3
Supportive care
- Pulmonary function tests (PFTs) checked before start of therapy, and then when cumulative dose of Carmustine (BCNU) reaches 800 mg/m2 and 1200 mg/m2
8-week cycles, with no more than a maximum cumulative dose of 1500 mg/m2 Carmustine (BCNU) given
References
- BTSG 69-01: Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Norrell HA, Owens G, Ransohoff J, Wilson CB, Gehan EA, Strike TA. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: a cooperative clinical trial. J Neurosurg. 1978 Sep;49(3):333-43. link to original article PubMed
- BTSG 72-01: Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J 2nd, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med. 1980 Dec 4;303(23):1323-9. link to original article PubMed
- SWOG S7703: Eyre HJ, Eltringham JR, Gehan EA, Vogel FS, Al-Sarraf M, Talley RW, Costanzi JJ, Athens JW, Oishi N, Fletcher WS. Randomized comparisons of radiotherapy and carmustine versus procarbazine versus dacarbazine for the treatment of malignant gliomas following surgery: a Southwest Oncology Group Study. Cancer Treat Rep. 1986 Sep;70(9):1085-90. PubMed
- BTCG 8001: Shapiro WR, Green SB, Burger PC, Mahaley MS Jr, Selker RG, VanGilder JC, Robertson JT, Ransohoff J, Mealey J Jr, Strike TA, Pistenmaa DA. Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma: Brain Tumor Cooperative Group Trial 8001. J Neurosurg. 1989 Jul;71(1):1-9. link to original article contains verified protocol PubMed
- Dinapoli RP, Brown LD, Arusell RM, Earle JD, O'Fallon JR, Buckner JC, Scheithauer BW, Krook JE, Tschetter LK, Maier JA, Pfeifle DM, Gesme DH. Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma. J Clin Oncol. 1993 Jul;11(7):1316-21. link to original article PubMed
- Buckner JC, Schomberg PJ, McGinnis WL, Cascino TL, Scheithauer BW, O'Fallon JR, Morton RF, Kuross SA, Mailliard JA, Hatfield AK, Cole JT, Steen PD, Bernath AM. A phase III study of radiation therapy plus carmustine with or without recombinant interferon-alpha in the treatment of patients with newly diagnosed high-grade glioma. Cancer. 2001 Jul 15;92(2):420-33. link to original article PubMed
- ECOG E2394: Grossman SA, O'Neill A, Grunnet M, Mehta M, Pearlman JL, Wagner H, Gilbert M, Newton HB, Hellman R; ECOG. Phase III study comparing three cycles of infusional carmustine and cisplatin followed by radiation therapy with radiation therapy and concurrent carmustine in patients with newly diagnosed supratentorial glioblastoma multiforme: Eastern Cooperative Oncology Group Trial 2394. J Clin Oncol. 2003 Apr 15;21(8):1485-91. link to original article PubMed
- NCCTG 93-72-52/SWOG S9503: Buckner JC, Ballman KV, Michalak JC, Burton GV, Cascino TL, Schomberg PJ, Hawkins RB, Scheithauer BW, Sandler HM, Marks RS, O'Fallon JR; North Central Cancer Treatment Group; SWOG. Phase III trial of carmustine and cisplatin compared with carmustine alone and standard radiation therapy or accelerated radiation therapy in patients with glioblastoma multiforme: North Central Cancer Treatment Group 93-72-52 and Southwest Oncology Group 9503 Trials. J Clin Oncol. 2006 Aug 20;24(24):3871-9. link to original article PubMed
- SWOG S0001: Blumenthal DT, Rankin C, Stelzer KJ, Spence AM, Sloan AE, Moore DF Jr, Padula GD, Schulman SB, Wade ML, Rushing EJ. A Phase III study of radiation therapy (RT) and O⁶-benzylguanine + BCNU versus RT and BCNU alone and methylation status in newly diagnosed glioblastoma and gliosarcoma: Southwest Oncology Group (SWOG) study S0001. Int J Clin Oncol. 2015 Aug;20(4):650-8. Epub 2014 Nov 19. link to original article link to PMC article PubMed
- RTOG 9006: Ali AN, Zhang P, Yung WKA, Chen Y, Movsas B, Urtasun RC, Jones CU, Choi KN, Michalski JM, Fischbach AJ, Markoe AM, Schultz CJ, Penas-Prado M, Garg MK, Hartford AC, Kim HE, Won M, Curran WJ Jr. NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients. J Neurooncol. 2018 Mar;137(1):39-47. Epub 2018 Feb 5. link to original article PubMed
Lomustine, Temozolomide, RT
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Lomustine, Temozolomide, RT: Lomustine, Temozolomide, Radiation Therapy
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Herrlinger et al. 2019 (CeTeG/NOA-09) | Phase III (E-esc) | Temozolomide & RT | Seems to have superior OS |
Note: see paper for dose adjustments to temozolomide after cycle 1.
Preceding treatment
Chemotherapy
- Lomustine (CCNU) 100 mg/m2 PO once on day 1
- Temozolomide (Temodar) 100 mg/m2 PO once per day on days 2 to 6
42-day cycle for up to 6 cycles
Radiotherapy
- External beam radiotherapy 59 to 60 Gy in 30 to 33 fractions
6- to 7-week course
References
- CeTeG/NOA-09: Herrlinger U, Tzaridis T, Mack F, Steinbach JP, Schlegel U, Sabel M, Hau P, Kortmann RD, Krex D, Grauer O, Goldbrunner R, Schnell O, Bähr O, Uhl M, Seidel C, Tabatabai G, Kowalski T, Ringel F, Schmidt-Graf F, Suchorska B, Brehmer S, Weyerbrock A, Renovanz M, Bullinger L, Galldiks N, Vajkoczy P, Misch M, Vatter H, Stuplich M, Schäfer N, Kebir S, Weller J, Schaub C, Stummer W, Tonn JC, Simon M, Keil VC, Nelles M, Urbach H, Coenen M, Wick W, Weller M, Fimmers R, Schmid M, Hattingen E, Pietsch T, Coch C, Glas M; Neurooncology Working Group of the German Cancer Society. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet. 2019 Feb 16;393(10172):678-688. Epub 2019 Feb 14. link to original article contains verified protocol PubMed
Nimustine & RT
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Nimustine & RT: Nimustine & Radiation Therapy
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Shibui et al. 2012 (JCOG 0305) | Phase III (C) | Nimustine, Procarbazine, RT | Did not meet primary endpoint of OS |
Note: this is of historic interest; ACNU is not generally available outside of Japan.
Preceding treatment
Chemotherapy
Radiotherapy
References
- JCOG 0305: Shibui S, Narita Y, Mizusawa J, Beppu T, Ogasawara K, Sawamura Y, Kobayashi H, Nishikawa R, Mishima K, Muragaki Y, Maruyama T, Kuratsu J, Nakamura H, Kochi M, Minamida Y, Yamaki T, Kumabe T, Tominaga T, Kayama T, Sakurada K, Nagane M, Kobayashi K, Nakamura H, Ito T, Yazaki T, Sasaki H, Tanaka K, Takahashi H, Asai A, Todo T, Wakabayashi T, Takahashi J, Takano S, Fujimaki T, Sumi M, Miyakita Y, Nakazato Y, Sato A, Fukuda H, Nomura K. Randomized trial of chemoradiotherapy and adjuvant chemotherapy with nimustine (ACNU) versus nimustine plus procarbazine for newly diagnosed anaplastic astrocytoma and glioblastoma (JCOG0305). Cancer Chemother Pharmacol. 2013 Feb;71(2):511-21. Epub 2012 Dec 11. link to original article PubMed
Radiation therapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Urtasun et al. 1976 | Randomized (C) | Metronidazole & RT | Seems to have inferior OS | |
Walker et al. 1978 (BTSG 69-01) | Phase III (E-esc) | 1. Best supportive care | Seems to have superior OS | |
2. Carmustine | Might have superior OS | |||
3. Carmustine & RT | Did not meet primary endpoint of OS50% | |||
Walker et al. 1980 (BTSG 72-01) | Phase III (C) | 1. Carmustine & RT 2. Semustine & RT |
Did not meet primary endpoint of OS | |
3. Semustine | Seems to have superior OS | |||
Stupp et al. 2005 (EORTC 22981/26981; NCIC CTG CE.3) | 2000-2002 | Phase III (C) | Temozolomide & RT, then Temozolomide | Inferior OS |
Adjuvant radiotherapy alone.
Preceding treatment
Radiotherapy
References
- Urtasun R, Band P, Chapman JD, Feldstein ML, Mielke B, Fryer C. Radiation and high-dose metronidazole in supratentorial glioblastomas. N Engl J Med. 1976 Jun 17;294(25):1364-7. link to original article PubMed
- BTSG 69-01: Walker MD, Alexander E Jr, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Norrell HA, Owens G, Ransohoff J, Wilson CB, Gehan EA, Strike TA. Evaluation of BCNU and/or radiotherapy in the treatment of anaplastic gliomas: a cooperative clinical trial. J Neurosurg. 1978 Sep;49(3):333-43. link to original article PubMed
- BTSG 72-01: Walker MD, Green SB, Byar DP, Alexander E Jr, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MS Jr, Mealey J Jr, Owens G, Ransohoff J 2nd, Robertson JT, Shapiro WR, Smith KR Jr, Wilson CB, Strike TA. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med. 1980 Dec 4;303(23):1323-9. link to original article PubMed
- EORTC 22981/26981; NCIC CTG CE.3: Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; EORTC 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 Mar 10;352(10):987-96. link to original article contains verified protocol PubMed
- Biomarker analysis: Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. link to original article PubMed
- Update: Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; EORTC Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. Epub 2009 Mar 9. link to original article PubMed
Temozolomide & RT
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Temozolomide & RT: Temozolomide & Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stupp et al. 2005 (EORTC 22981/26981; NCIC CTG CE.3) | 2000-2002 | Phase III (E-RT-esc) | See link | See link |
Gilbert et al. 2013 (RTOG 0525) | Non-randomized portion of RCT | |||
Gilbert et al. 2014 (RTOG 0825) | Phase III (C) | See link | See link | |
Chinot et al. 2014 (AVAglio) | Phase III (C) | See link | See link | |
Stupp et al. 2014 (CENTRIC) | Phase III (C) | Cilengitide, Temozolomide, RT | Did not meet primary endpoint of OS | |
Westphal et al. 2015 (OSAG 101-BSA-05) | Phase III (C) | Temozolomide, Nimotuzumab, RT | Did not meet primary endpoints of PFS12/PFS50% | |
Kong et al. 2017 (IcmLCBT_301) | Phase III (C) | Temozolomide & RT with CIK cells | Seems to have inferior PFS |
Biomarker eligibility criteria
- Patients in CENTRIC were required to have methylated MGMT promoter.
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO or IV once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days
Supportive medications
- PCP prophylaxis with ONE of the following:
- Trimethoprim/Sulfamethoxazole (Bactrim)
- Pentamidine (Nebupent) 300 mg nebulized inhaled
- Metoclopramide (Reglan) or 5-HT3 antagonist recommended before the initial doses of radiation therapy & temozolomide
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 30 fractions, for a total dose of 60 Gy
6-week course
Subsequent treatment
- Most protocols: Temozolomide maintenance, 4 weeks after completion of radiation therapy
- RTOG 0525: Temozolomide versus dose-dense temozolomide maintenance
References
- EORTC 22981/26981; NCIC CTG CE.3: Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; EORTC 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 Mar 10;352(10):987-96. link to original article contains verified protocol PubMed
- Biomarker analysis: Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. link to original article PubMed
- Update: Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; EORTC Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. Epub 2009 Mar 9. link to original article PubMed
- RTOG 0525: Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, Mahajan A, Schultz CJ, Erridge S, Baumert B, Hopkins KI, Tzuk-Shina T, Brown PD, Chakravarti A, Curran WJ Jr, Mehta MP. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013 Nov 10;31(32):4085-91. Epub 2013 Oct 7. link to original article link to PMC article contains verified protocol PubMed
- RTOG 0825: Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. link to original article link to PMC article PubMed
- AVAglio: Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. link to original article contains protocol PubMed
- CENTRIC: Stupp R, Hegi ME, Gorlia T, Erridge SC, Perry J, Hong YK, Aldape KD, Lhermitte B, Pietsch T, Grujicic D, Steinbach JP, Wick W, Tarnawski R, Nam DH, Hau P, Weyerbrock A, Taphoorn MJ, Shen CC, Rao N, Thurzo L, Herrlinger U, Gupta T, Kortmann RD, Adamska K, McBain C, Brandes AA, Tonn JC, Schnell O, Wiegel T, Kim CY, Nabors LB, Reardon DA, van den Bent MJ, Hicking C, Markivskyy A, Picard M, Weller M; EORTC; Canadian Brain Tumor Consortium; CENTRIC study team. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1100-8. Epub 2014 Aug 19. link to original article PubMed
- OSAG 101-BSA-05: Westphal M, Heese O, Steinbach JP, Schnell O, Schackert G, Mehdorn M, Schulz D, Simon M, Schlegel U, Senft C, Geletneky K, Braun C, Hartung JG, Reuter D, Metz MW, Bach F, Pietsch T. A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer. 2015 Mar;51(4):522-32. Epub 2015 Jan 20. link to original article PubMed
- GLARIUS: Herrlinger U, Schäfer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tüttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: the randomized GLARIUS trial. J Clin Oncol. 2016 May 10;34(14):1611-9. Epub 2016 Mar 14. link to original article PubMed
- IcmLCBT_301: Kong DS, Nam DH, Kang SH, Lee JW, Chang JH, Kim JH, Lim YJ, Koh YC, Chung YG, Kim JM, Kim CH. Phase III randomized trial of autologous cytokine-induced killer cell immunotherapy for newly diagnosed glioblastoma in Korea. Oncotarget. 2017 Jan 24;8(4):7003-7013. link to original article link to PMC article contains verified protocol PubMed
- HERBY: Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, Le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G. Phase II, Open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol. 2018 Apr 1;36(10):951-958. Epub 2018 Feb 7. link to original article PubMed
Adjuvant therapy, elderly or poor performance status patients
Best supportive care
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Keime-Guibert et al. 2007 | Phase III (C) | RT x 50 Gy | Inferior OS |
No antineoplastic therapy after primary surgery.
Preceding treatment
References
- Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Meneï P, Loiseau H, Bernier V, Honnorat J, Barrié M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY; Association of French-Speaking Neuro-Oncologists. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35. link to original article contains protocol PubMed
Radiation therapy
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Regimen variant #1, hypofractionated (34 Gy)
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Malmström et al. 2012 | Phase III (E-switch-ic) | 1. RT; standard | Did not meet primary endpoint of OS |
2. Temozolomide | Did not meet primary endpoint of OS |
Preceding treatment
Radiotherapy
- External beam radiotherapy 10 x 3.40 Gy fractions, five days per week, for a total dose of 34 Gy
2-week course
Regimen variant #2, abbreviated course (40 Gy)
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Roa et al. 2004 | Randomized Phase II (E-switch-de-esc) | RT; standard (60 Gy) | Did not meet primary endpoint of OS |
Perry et al. 2017 (NCIC CTG CE.6) | Phase III (C) | Temozolomide & LDRT | Inferior OS |
Note: Roa et al. 2004 was closed early due to poor accrual.
Preceding treatment
Radiotherapy
- External beam radiotherapy 15 x 2.67 Gy fractions, five days per week, for a total dose of 40.05 Gy
3-week course
Regimen variant #3, standard course (50.4 Gy)
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Keime-Guibert et al. 2007 | Phase III (E-esc) | Best supportive care | Superior OS |
Preceding treatment
Radiotherapy
- External beam radiotherapy 28 x 1.80 Gy fractions, five days per week, for a total dose of 50.4 Gy
5.5-week course
Regimen variant #4, standard course (60 Gy)
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Roa et al. 2004 | Randomized Phase II (C) | RT; abbreviated (40 Gy) | Did not meet primary endpoint of OS |
Malmström et al. 2012 | Phase III (C) | 1. RT; hypofractionated | Did not meet primary endpoint of OS |
2. Temozolomide | Inferior OS |
Note: Roa et al. 2004 was closed early due to poor accrual.
Preceding treatment
Radiotherapy
- External beam radiotherapy 30 x 2.00 Gy fractions, five days per week, for a total dose of 60 Gy
6-week course
References
- Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG, Forsyth P. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol. 2004 May 1;22(9):1583-8. Epub 2004 Mar 29. link to original article contains protocol PubMed
- Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Meneï P, Loiseau H, Bernier V, Honnorat J, Barrié M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY; Association of French-Speaking Neuro-Oncologists. Radiotherapy for glioblastoma in the elderly. N Engl J Med. 2007 Apr 12;356(15):1527-35. link to original article contains protocol PubMed
- Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R; Nordic Clinical Brain Tumour Study Group. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012 Sep;13(9):916-26. link to original article contains protocol PubMed
- NCIC CTG CE.6: Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D, Rossiter JP, Sahgal A, Hirte H, Laigle-Donadey F, Franceschi E, Chinot O, Golfinopoulos V, Fariselli L, Wick A, Feuvret L, Back M, Tills M, Winch C, Baumert BG, Wick W, Ding K, Mason WP; Trial Investigators. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017 Mar 16;376(11):1027-1037. link to original article PubMed
Temozolomide monotherapy
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Malmström et al. 2012 | Phase III (E-switch-ooc) | 1. Hypofractionated RT | Did not meet primary endpoint of OS |
2. Standard RT | Superior OS |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 6 cycles
References
- Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R; Nordic Clinical Brain Tumour Study Group. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol. 2012 Sep;13(9):916-26. link to original article contains verified protocol PubMed
Temozolomide & low-dose RT
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Temozolomide & LDRT: Temozolomide & Low-Dose Radiation Therapy
Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Perry et al. 2017 (NCIC CTG CE.6) | Phase III (E-switch-esc) | Radiotherapy | Superior OS |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day, starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 21 days
Radiotherapy
- Concurrent radiation therapy, 2.67 Gy fractions x 15 fractions, for a total dose of 40.05 Gy
3-week course
Subsequent treatment
References
- NCIC CTG CE.6: Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D, Rossiter JP, Sahgal A, Hirte H, Laigle-Donadey F, Franceschi E, Chinot O, Golfinopoulos V, Fariselli L, Wick A, Feuvret L, Back M, Tills M, Winch C, Baumert BG, Wick W, Ding K, Mason WP; Trial Investigators. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017 Mar 16;376(11):1027-1037. link to original article contains verified protocol PubMed
Maintenance after first-line therapy
Irinotecan & Bevacizumab
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Regimen
Study | Evidence |
---|---|
Herrlinger et al. 2016 (GLARIUS) | Non-randomized portion of RCT |
To be completed
Preceding treatment
Chemotherapy
References
- GLARIUS: Herrlinger U, Schäfer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tüttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: the randomized GLARIUS trial. J Clin Oncol. 2016 May 10;34(14):1611-9. Epub 2016 Mar 14. link to original article PubMed
Temozolomide monotherapy
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Regimen variant #1, 6 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stupp et al. 2005 (EORTC 22981/26981; NCIC CTG CE.3) | 2000-2002 | Phase III (E-RT-esc) | See link | See link |
Gilbert et al. 2014 (RTOG 0825) | Phase III (C) | See link | See link | |
Chinot et al. 2014 (AVAglio) | Phase III (C) | See link | See link | |
Stupp et al. 2015 (EF-14) | Phase III (C) | Temozolomide & NovoTTF-100A | Inferior OS | |
Kong et al. 2017 (IcmLCBT_301) | Non-randomized portion of RCT |
Note: patients in RTOG 0825 could extend maintenance to 12 cycles if no major adverse events and evidence of ongoing benefit.
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) as follows:
- Cycle 1: 150 mg/m2 PO once per day on days 1 to 5
- If tolerated, in cycles 2 to 6: 200 mg/m2 PO once per day on days 1 to 5
Supportive medications
- Metoclopramide (Reglan) or 5-HT3 antagonist required
28-day cycle for 6 cycles
Regimen variant #2, 12 cycles
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Gilbert et al. 2013 (RTOG 0525) | Phase III (C) | Dose-dense Temozolomide | Did not meet primary endpoint of OS |
Perry et al. 2017 (NCIC CTG CE.6) | Non-randomized portion of RCT | ||
Weller et al. 2017 (ACT IV) | Phase III (C) | Rindopepimut & Temozolomide | Did not meet primary endpoint of OS |
Grill et al. 2018 (HERBY) | Randomized Phase II (C) | See link | See link |
Note: treatment in ACT IV was given for a minimum of 6 cycles.
Preceding treatment
- RTOG 0525: Surgery, then adjuvant temozolomide & RT
- NCIC CTG CE.6: Surgery, then adjuvant temozolomide & low-dose RT
- ACT IV: Resection
- HERBY: Surgery, then adjuvant temozolomide & RT
Chemotherapy
- Temozolomide (Temodar) 150 to 200 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 12 cycles
References
- EORTC 22981/26981; NCIC CTG CE.3: Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; EORTC 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 Mar 10;352(10):987-96. link to original article contains verified protocol PubMed
- Biomarker analysis: Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. link to original article PubMed
- Update: Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; EORTC Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. Epub 2009 Mar 9. link to original article PubMed
- RTOG 0525: Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, Mahajan A, Schultz CJ, Erridge S, Baumert B, Hopkins KI, Tzuk-Shina T, Brown PD, Chakravarti A, Curran WJ Jr, Mehta MP. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013 Nov 10;31(32):4085-91. Epub 2013 Oct 7. link to original article link to PMC article contains verified protocol PubMed
- RTOG 0825: Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. link to original article link to PMC article PubMed
- AVAglio: Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. link to original article contains protocol PubMed
- EF-14: Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015 Dec 15;314(23):2535-43. link to original article contains protocol PubMed
- Update: Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran DD, Brem S, Hottinger AF, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017 Dec 19;318(23):2306-2316. link to original article PubMed
- GLARIUS: Herrlinger U, Schäfer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, Friedrich F, Rohde V, Ringel F, Schlegel U, Sabel M, Ronellenfitsch MW, Uhl M, Maciaczyk J, Grau S, Schnell O, Hänel M, Krex D, Vajkoczy P, Gerlach R, Kortmann RD, Mehdorn M, Tüttenberg J, Mayer-Steinacker R, Fietkau R, Brehmer S, Mack F, Stuplich M, Kebir S, Kohnen R, Dunkl E, Leutgeb B, Proescholdt M, Pietsch T, Urbach H, Belka C, Stummer W, Glas M. Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: the randomized GLARIUS trial. J Clin Oncol. 2016 May 10;34(14):1611-9. Epub 2016 Mar 14. link to original article PubMed
- IcmLCBT_301: Kong DS, Nam DH, Kang SH, Lee JW, Chang JH, Kim JH, Lim YJ, Koh YC, Chung YG, Kim JM, Kim CH. Phase III randomized trial of autologous cytokine-induced killer cell immunotherapy for newly diagnosed glioblastoma in Korea. Oncotarget. 2017 Jan 24;8(4):7003-7013. link to original article link to PMC article contains verified protocol PubMed
- NCIC CTG CE.6: Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D, Rossiter JP, Sahgal A, Hirte H, Laigle-Donadey F, Franceschi E, Chinot O, Golfinopoulos V, Fariselli L, Wick A, Feuvret L, Back M, Tills M, Winch C, Baumert BG, Wick W, Ding K, Mason WP; Trial Investigators. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med. 2017 Mar 16;376(11):1027-1037. link to original article contains verified protocol PubMed
- ACT IV: Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J, O'Rourke DM, Wong M, Hamilton MG, Finocchiaro G, Perry J, Wick W, Green J, He Y, Turner CD, Yellin MJ, Keler T, Davis TA, Stupp R, Sampson JH; ACT IV trial investigators. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1373-1385. Epub 2017 Aug 23. link to original article contains protocol PubMed
- HERBY: Grill J, Massimino M, Bouffet E, Azizi AA, McCowage G, Cañete A, Saran F, Le Deley MC, Varlet P, Morgan PS, Jaspan T, Jones C, Giangaspero F, Smith H, Garcia J, Elze MC, Rousseau RF, Abrey L, Hargrave D, Vassal G. Phase II, open-label, randomized, multicenter trial (HERBY) of bevacizumab in pediatric patients with newly diagnosed high-grade glioma. J Clin Oncol. 2018 Apr 1;36(10):951-958. Epub 2018 Feb 7. link to original article contains protocol PubMed
Temozolomide & NovoTTF-100A
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Stupp et al. 2015 (EF-14) | Phase III (E-esc) | Temozolomide | Superior OS |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) as follows:
- Cycle 1: 150 mg/m2 PO once per day on days 1 to 5
- If tolerated, in cycles 2 to 6: 200 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 cycles
Tumor treating fields, CNS
- NovoTTF-100A system (Optune) for at least 18 hours per day
Up to to 24-month course
References
- EF-14: Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015 Dec 15;314(23):2535-43. link to original article contains protocol PubMed
- Update: Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, Di Meco F, Lieberman F, Zhu JJ, Stragliotto G, Tran DD, Brem S, Hottinger AF, Kirson ED, Lavy-Shahaf G, Weinberg U, Kim CY, Paek SH, Nicholas G, Bruna J, Hirte H, Weller M, Palti Y, Hegi ME, Ram Z. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017 Dec 19;318(23):2306-2316. link to original article PubMed
Recurrent disease, non-curative therapy, randomized data
Carmustine monotherapy
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Regimen
Study | Evidence |
---|---|
Fewer et al. 1972 | Retrospective |
Brandes et al. 2004a | Phase II |
Chemotherapy
- Carmustine (BCNU) 80 mg/m2 IV once per day on days 1 to 3
Supportive medications
- Antiemesis prophylaxis with Ondansetron (Zofran)
- Steroids at lowest dose necessary
8-week cycle for up to 6 cycles
References
- Retrospective: Fewer D, Wilson CB, Boldrey EB, Enot KJ, Powell MR. The chemotherapy of brain tumors: clinical experience with carmustine (BCNU) and vincristine. JAMA. 1972 Oct 30;222(5):549-52. link to original article PubMed
- Brandes AA, Tosoni A, Amistà P, Nicolardi L, Grosso D, Berti F, Ermani M. How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology. 2004 Oct 12;63(7):1281-4. link to original article contains verified protocol PubMed
Gliadel wafer monotherapy
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Brem et al. 1995 | Phase III (E-esc) | Placebo wafer | Superior OS |
Westphal et al. 2003 | Phase III (E-esc) | Placebo wafer | Seems to have superior OS |
Kunwar et al. 2010 (PRECISE) | Phase III (C) | Cintredekin besudotox | Did not meet primary endpoint of OS |
Chemotherapy, CNS
References
- Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G, Muller P, Morawetz R, Schold SC; Polymer-Brain Tumor Treatment Group. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. Lancet. 1995 Apr 22;345(8956):1008-12. link to original article PubMed
- Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, Whittle IR, Jääskeläinen J, Ram Z. A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol. 2003 Apr;5(2):79-88. link to original article link to PMC article PubMed
- PRECISE: Kunwar S, Chang S, Westphal M, Vogelbaum M, Sampson J, Barnett G, Shaffrey M, Ram Z, Piepmeier J, Prados M, Croteau D, Pedain C, Leland P, Husain SR, Joshi BH, Puri RK; PRECISE Study Group. Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol. 2010 Aug;12(8):871-81. Epub 2010 Feb 4. link to original article link to PMC article PubMed
Hydroxyurea monotherapy
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Dresemann et al. 2009 | Phase III (C) | Hydroxyurea & Imatinib | Did not meet primary endpoint of PFS |
Chemotherapy
References
- Dresemann G, Weller M, Rosenthal MA, Wedding U, Wagner W, Engel E, Heinrich B, Mayer-Steinacker R, Karup-Hansen A, Fluge O, Nowak A, Mehdorn M, Schleyer E, Krex D, Olver IN, Steinbach JP, Hosius C, Sieder C, Sorenson G, Parker R, Nikolova Z. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. J Neurooncol. 2010 Feb;96(3):393-402. Epub 2009 Aug 18. link to original article PubMed
Hydroxyurea & Imatinib
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Dresemann et al. 2005 | Non-randomized | ||
Dresemann et al. 2009 | Phase III (E-esc) | Hydroxyurea | Did not meet primary endpoint of PFS |
Note: this combination did not succeed in the randomized phase III trial.
Chemotherapy
- Hydroxyurea (Hydrea) 500 mg PO twice per day
- Imatinib (Gleevec) 400 mg PO once per day
Continued indefinitely
References
- Dresemann G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series. Ann Oncol. 2005 Oct;16(10):1702-8. Epub 2005 Jul 20. link to original article contains verified protocol PubMed
- Dresemann G, Weller M, Rosenthal MA, Wedding U, Wagner W, Engel E, Heinrich B, Mayer-Steinacker R, Karup-Hansen A, Fluge O, Nowak A, Mehdorn M, Schleyer E, Krex D, Olver IN, Steinbach JP, Hosius C, Sieder C, Sorenson G, Parker R, Nikolova Z. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. J Neurooncol. 2010 Feb;96(3):393-402. Epub 2009 Aug 18. link to original article PubMed
Lomustine monotherapy
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Regimen variant #1, 100 mg/m2
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Wick et al. 2010 (JCBF) | Phase III (C) | Enzastaurin | Did not meet primary endpoint of PFS |
Note: this was the lower bound of the range specified in the trial.
Chemotherapy
- Lomustine (CCNU) 100 mg/m2 PO once on day 1
Supportive medications
- Enzyme-inducing antiepileptic drugs (EIAEDs) needed to be discontinued 14 days before enrolling in the trial
42-day cycles
Regimen variant #2, 110 mg/m2, uncapped
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Batchelor et al. 2013 (REGAL) | Phase III (C) | 1. Cediranib 2. Cediranib & Lomustine |
Did not meet primary endpoint of PFS |
Chemotherapy
- Lomustine (CCNU) 110 mg/m2 PO once on day 1
42-day cycles
Regimen variant #3, 110 mg/m2, capped
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Taal et al. 2014 (BELOB) | Randomized Phase II (C) | Lomustine & Bevacizumab | Not reported | |
Wick et al. 2017 (EORTC 26101) | 2011-2014 | Phase III (C) | Lomustine & Bevacizumab | Did not meet primary endpoint of OS |
Chemotherapy
- Lomustine (CCNU) 110 mg/m2 (maximum dose of 200 mg) PO once on day 1
42-day cycles
Regimen variant #4, 130 mg/m2
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Bleehen et al. 1989 | Phase III (C) | Benznidazole & Lomustine | Did not meet endpoint |
Wick et al. 2010 (JCBF) | Phase III (C) | Enzastaurin | Did not meet primary endpoint of PFS |
Note: this was the upper bound of the range specified in JCBF.
Chemotherapy
- Lomustine (CCNU) 130 mg/m2 PO once on day 1
Supportive medications
- Enzyme-inducing antiepileptic drugs (EIAEDs) needed to be discontinued 14 days before enrolling in JCBF
42-day cycle for 6 cycles or indefinitely (JCBF)
References
- Bleehen NM, Freedman LS, Stenning SP. A randomized study of CCNU with and without benznidazole in the treatment of recurrent grades 3 and 4 astrocytoma: report to the Medical Research Council by the Brain Tumor Working Party. Int J Radiat Oncol Biol Phys. 1989 Apr;16(4):1077-81. link to original article PubMed
- JCBF: Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, Mason W, Weller M, Hong S, Musib L, Liepa AM, Thornton DE, Fine HA. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010 Mar 1;28(7):1168-74. Epub 2010 Feb 1. link to original article contains verified protocol link to PMC article PubMed
- REGAL: Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS, Degroot J, Gattamaneni R, Cher L, Rosenthal M, Payer F, Jürgensmeier JM, Jain RK, Sorensen AG, Xu J, Liu Q, van den Bent M. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013 Sep 10;31(26):3212-8. Epub 2013 Aug 12. link to original article contains verified protocol link to PMC article PubMed
- BELOB: Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014 Aug;15(9):943-53. Epub 2014 Jul 15. link to original article contains verified protocol PubMed
- HRQoL analysis: Dirven L, van den Bent MJ, Bottomley A, van der Meer N, van der Holt B, Vos MJ, Walenkamp AM, Beerepoot LV, Hanse MC, Reijneveld JC, Otten A, de Vos FY, Smits M, Bromberg JE, Taal W, Taphoorn MJ; Dutch Neuro-Oncology Group. The impact of bevacizumab on health-related quality of life in patients treated for recurrent glioblastoma: results of the randomised controlled phase 2 BELOB trial. Eur J Cancer. 2015 Jul;51(10):1321-30. Epub 2015 Apr 17. PubMed
- EORTC 26101: Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017 Nov 16;377(20):1954-1963. link to original article contains verified protocol PubMed
Lomustine & Bevacizumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Taal et al. 2014 (BELOB) | Randomized Phase II (E-esc) | Lomustine | Not reported | |
Wick et al. 2017 (EORTC 26101) | 2011-2014 | Phase III (E-RT-esc) | Lomustine | Did not meet primary endpoint of OS |
Chemotherapy
42-day cycles
References
- BELOB: Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014 Aug;15(9):943-53. Epub 2014 Jul 15. link to original article contains verified protocol PubMed
- HRQoL analysis: Dirven L, van den Bent MJ, Bottomley A, van der Meer N, van der Holt B, Vos MJ, Walenkamp AM, Beerepoot LV, Hanse MC, Reijneveld JC, Otten A, de Vos FY, Smits M, Bromberg JE, Taal W, Taphoorn MJ; Dutch Neuro-Oncology Group. The impact of bevacizumab on health-related quality of life in patients treated for recurrent glioblastoma: results of the randomised controlled phase 2 BELOB trial. Eur J Cancer. 2015 Jul;51(10):1321-30. Epub 2015 Apr 17. PubMed
- EORTC 26101: Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, Brandes AA, Taal W, Domont J, Idbaih A, Campone M, Clement PM, Stupp R, Fabbro M, Le Rhun E, Dubois F, Weller M, von Deimling A, Golfinopoulos V, Bromberg JC, Platten M, Klein M, van den Bent MJ. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017 Nov 16;377(20):1954-1963. link to original article contains verified protocol PubMed
NovoTTF-100A monotherapy
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Regimen
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Stupp et al. 2012 (EF-11) | Phase III (E-switch-ooc) | Investigator's choice | Did not meet primary endpoint of OS |
Tumor treating fields, CNS
References
- EF-11: Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbalý V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. Epub 2012 May 18. link to original article PubMed
PCV
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PCV: Procarbazine, CCNU (Lomustine), Vincristine
Regimen variant #1, 60/110/1.4
Study | Evidence |
---|---|
Levin et al. 1980 | Non-randomized |
Chemotherapy
- Procarbazine (Matulane) 60 mg/m2 PO once per day on days 8 to 21
- Lomustine (CCNU) 110 mg/m2 PO once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 8 & 29
42-day cycles
Regimen variant #2, 100/100/1.5
Study | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|
Brada et al. 2010 | Phase III (C) | Temozolomide | Did not meet primary endpoints of PFS3/OS |
Chemotherapy
- Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 10
- Lomustine (CCNU) 100 mg/m2 PO once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once on day 1
42-day cycle for up to 6 cycles
References
- Levin VA, Edwards MS, Wright DC, Seager ML, Schimberg TP, Townsend JJ, Wilson CB. Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):237-44. contains protocol PubMed
- Brada M, Stenning S, Gabe R, Thompson LC, Levy D, Rampling R, Erridge S, Saran F, Gattamaneni R, Hopkins K, Beall S, Collins VP, Lee SM. Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol. 2010 Oct 20;28(30):4601-8. Epub 2010 Sep 20. link to original article contains verified protocol PubMed
Recurrent disease, non-curative therapy, non-randomized or retrospective data
Bevacizumab monotherapy
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Regimen variant #1
Study | Years of enrollment | Evidence |
---|---|---|
Friedman et al. 2009 (AVF3708g) | 2006-2007 | Phase II (RT) |
Chemotherapy
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
14-day cycle for up to 52 cycles (2 years)
Regimen variant #2
Study | Years of enrollment | Evidence |
---|---|---|
Kreisl et al. 2008 (NCI 06-C-0064E) | 2006-2007 | Phase II (RT) |
Chemotherapy
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Subsequent treatment
- Upon progression: Irinotecan & Bevacizumab
References
- NCI 06-C-0064E: Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. Epub 2008 Dec 29. link to original article contains verified protocol link to PMC article PubMed
- AVF3708g: Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. link to original article contains verified protocol PubMed
- BELOB: Taal W, Oosterkamp HM, Walenkamp AM, Dubbink HJ, Beerepoot LV, Hanse MC, Buter J, Honkoop AH, Boerman D, de Vos FY, Dinjens WN, Enting RH, Taphoorn MJ, van den Berkmortel FW, Jansen RL, Brandsma D, Bromberg JE, van Heuvel I, Vernhout RM, van der Holt B, van den Bent MJ. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014 Aug;15(9):943-53. Epub 2014 Jul 15. link to original article PubMed
- HRQoL analysis: Dirven L, van den Bent MJ, Bottomley A, van der Meer N, van der Holt B, Vos MJ, Walenkamp AM, Beerepoot LV, Hanse MC, Reijneveld JC, Otten A, de Vos FY, Smits M, Bromberg JE, Taal W, Taphoorn MJ; Dutch Neuro-Oncology Group. The impact of bevacizumab on health-related quality of life in patients treated for recurrent glioblastoma: results of the randomised controlled phase 2 BELOB trial. Eur J Cancer. 2015 Jul;51(10):1321-30. Epub 2015 Apr 17. PubMed
Carboplatin & Bevacizumab
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Regimen variant #1, q2wk bevacizumab
Study | Evidence |
---|---|
Norden et al. 2008 | Retrospective |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 to 6 IV (reference does not list schedule of carboplatin)
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
14-day cycles
Regimen variant #2, q4wk bevacizumab
Study | Evidence |
---|---|
Thompson et al. 2010 | Retrospective |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
28-day cycles
References
- Retrospective: Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008 Mar 4;70(10):779-87. link to original article PubMed
- Retrospective: Thompson EM, Dosa E, Kraemer DF, Neuwelt EA. Treatment with bevacizumab plus carboplatin for recurrent malignant glioma. Neurosurgery. 2010 Jul;67(1):87-93. link to original article link to PMC article PubMed
CART-EGFRvIII cells
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Regimen
Study | Evidence |
---|---|
O'Rourke et al. 2017 (UPCC 35313) | Phase I |
Immunotherapy
- Autologous CART-EGFRvIII cells, see paper for details
One treatment
References
- Phase I: O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, Martinez-Lage M, Brem S, Maloney E, Shen A, Isaacs R, Mohan S, Plesa G, Lacey SF, Navenot JM, Zheng Z, Levine BL, Okada H, June CH, Brogdon JL, Maus MV. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017 Jul 19;9(399). PubMed link to original article
Cyclophosphamide monotherapy
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Regimen
Study | Evidence |
---|---|
Chamberlain & Tsao-Wei 2004 | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 30 minutes once per day on days 1 & 2
Supportive medications
- Dexamethasone (Decadron) allowed for control of neurologic symptoms
- Ondansetron (Zofran) 0.15 mg/kg IV once per day on days 1 & 2, prior to Cyclophosphamide (Cytoxan)
- Dexamethasone (Decadron) 4 mg IV once per day on days 1 & 2, prior to Cyclophosphamide (Cytoxan)
- 1 liter normal saline IV over 2 hours once per day on days 1 & 2, prior to Cyclophosphamide (Cytoxan)
- Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
28-day cycles
References
- Chamberlain MC, Tsao-Wei DD. Salvage chemotherapy with cyclophosphamide for recurrent, temozolomide-refractory glioblastoma multiforme. Cancer. 2004 Mar 15;100(6):1213-20. link to original article contains verified protocol PubMed
Irinotecan monotherapy
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Regimen
Study | Evidence |
---|---|
Friedman et al. 1999 | Phase II |
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV once per day on days 1, 8, 15, 22
- If tolerated, dose could be increased to 150 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications
- Steroids at lowest dose necessary
- Avoid laxatives and magnesium-containing antacids due to potential for diarrhea
42-day cycles
References
- Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL. Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol. 1999 May;17(5):1516-25. link to original article contains verified protocol PubMed
Irinotecan & Bevacizumab
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Regimen variant #1, q2wk bev
Study | Evidence |
---|---|
Chen et al. 2007 | Pilot, >20 pts |
Vredenburgh et al. 2007 | Phase II |
Norden et al. 2008 | Phase II |
Kreisl et al. 2008 (NCI 06-C-0064E) | Phase II |
Friedman et al. 2009 (AVF3708g) | Phase II |
Note: AVF3708g described 6-week cycles in which treatment was every 2 weeks, given up to 104 weeks, and was otherwise identical, so its entry was consolidated with the other ones here.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once on day 1, given first
- Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 340 mg/m2 or 350 mg/m2 (Chen et al. 2007) IV over 90 minutes once on day 1, given first
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1, given second, 90 minutes after the start of irinotecan
- Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later
Supportive medications
- Steroids were generally maintained at the same dose
14-day cycles
Regimen variant #2, q3wk bev
Study | Evidence |
---|---|
Vredenburgh et al. 2007 | Phase II, <20 pts |
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 22, 29, given first
- Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 350 mg/m2 IV over 90 minutes once per day on days 1, 8, 22, 29, given first
- Bevacizumab (Avastin) 15 mg/kg IV once per day on days 1 & 22, given second, 90 minutes after the start of irinotecan
- Infusion time is 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later
Supportive medications
- Steroids were generally maintained at the same dose
42-day cycles
References
- Chen W, Delaloye S, Silverman DH, Geist C, Czernin J, Sayre J, Satyamurthy N, Pope W, Lai A, Phelps ME, Cloughesy T. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol. 2007 Oct 20;25(30):4714-21. link to original article contains verified protocol PubMed
- Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Wagner M, Bigner DD, Friedman AH, Friedman HS. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9. link to original article contains verified protocol PubMed
- Update: Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007 Oct 20;25(30):4722-9. link to original article contains verified protocol PubMed
- Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008 Mar 4;70(10):779-87. link to original article contains verified protocol PubMed
- NCI 06-C-0064E: Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. Epub 2008 Dec 29. link to original article link to PMC article contains protocol PubMed
- AVF3708g: Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. link to original article contains verified protocol PubMed
Procarbazine monotherapy
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Regimen variant #1, 125 mg/m2
Study | Evidence |
---|---|
Yung et al. 2000 | Phase II |
Note: this is the starting dose for patients who previously received chemotherapy; no instructions for dose escalation are given.
Chemotherapy
- Procarbazine (Matulane) 125 mg/m2 PO once per day on days 1 to 28
Supportive medications
- Steroids at lowest dose necessary
8-week cycle for up to 13 cycles (2 years)
Regimen variant #2, 150 mg/m2
Study | Evidence |
---|---|
Yung et al. 2000 | Phase II |
Note: this dosing is intended for patients who have never previously received chemotherapy.
Chemotherapy
- Procarbazine (Matulane) 150 mg/m2 PO once per day on days 1 to 28
- Patients who previously received chemotherapy started with 125 mg/m2 PO once per day on days 1 to 28
Supportive medications
- Steroids at lowest dose necessary
8-week cycle for up to 13 cycles (2 years)
References
- Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. A phase II study of temozolomide vs procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000 Sep;83(5):588-93. link to original article contains verified protocol link to PMC article PubMed
Temozolomide monotherapy
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Regimen variant #1, continuous
Study | Evidence |
---|---|
Perry et al. 2008 (RESCUE) | Phase II |
See paper for details of when this regimen is used.
Chemotherapy
- Temozolomide (Temodar) 50 mg/m2 PO once per day
Continued indefinitely
Regimen variant #2, 11 cycles
Study | Evidence |
---|---|
Nicholson et al. 2007 | Non-randomized |
Chemotherapy
- Temozolomide (Temodar) 150 to 200 mg/m2 PO once per day on days 1 to 5
- Patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 11 cycles
Regimen variant #3, 2 years
Study | Evidence |
---|---|
Yung et al. 2000 | Phase II |
Chemotherapy
- Temozolomide (Temodar) as follows:
- Patients who had never previously received chemotherapy: 200 mg/m2 PO once per day on days 1 to 5
- Patients who previously received chemotherapy started with 150 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 26 cycles (2 years)
References
- Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. A phase II study of temozolomide vs procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000 Sep;83(5):588-93. link to original article contains verified protocol link to PMC article PubMed
- Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH; Children's Oncology Group. 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 Oct 1;110(7):1542-50. link to original article contains verified protocol PubMed
- RESCUE: Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the "rescue" approach. Cancer. 2008 Oct 15;113(8):2152-7. link to original article contains verified protocol PubMed
- Update: Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, Shields C, Kirby S, Macdonald DR, Eisenstat DD, Thiessen B, Forsyth P, Pouliot JF. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20;28(12):2051-7. Epub 2010 Mar 22. link to original article contains verified protocol PubMed