Low-grade glioma
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| Section editor | |
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Seema Nagpal, MD Stanford University Palo Alto, CA, USA |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: pediatric regimens have been moved to a dedicated page:
7 regimens on this page
10 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
EANO
- European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas (2017) PubMed
- European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma (2017) PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Central Nervous System Cancers.
Adjuvant therapy
PCV
PCV: Procarbazine, CCNU (Lomustine), Vincristine
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Shaw et al. 2012 (RTOG 9802) | 1998-2002 | Phase 3 (E-esc) | Observation | Superior OS1 (primary endpoint) Median OS: 13.3 vs 7.8 y (HR 0.59) |
1Reported efficacy is based on the 2016 update.
Preceding treatment
- Definitive RT x 5400 cGy
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
8-week cycle for 6 cycles
References
- RTOG 9802: Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol. 2012 Sep 1;30(25):3065-70. Epub 2012 Jul 30. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00003375
- Update: Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary JP, Fisher BJ, Kim H, Murtha AD, Bell EH, Won M, Mehta MP, Curran WJ Jr. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 2016 Apr 7;374(14):1344-55. link to original article link to PMC article PubMed
Radiation therapy
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Shaw et al. 2012 (RTOG 9802) | 1998-2002 | Non-randomized part of phase 3 RCT | ||
| Baumert et al. 2016 (EORTC 22033-26033) | 2005-2010 | Phase 3 (C) | Temozolomide | Did not meet primary endpoint of PFS |
Note: Details here are from RTOG 9802.
Radiotherapy
- External beam radiotherapy with 180 cGy fractions given in 30 fractions, for a total dose of 5400 cGy
6-week course
Subsequent treatment
- RTOG 9802: Observation versus adjuvant PCV x 6
References
- RTOG 9802: Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta MP. Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol. 2012 Sep 1;30(25):3065-70. Epub 2012 Jul 30. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00003375
- Update: Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary JP, Fisher BJ, Kim H, Murtha AD, Bell EH, Won M, Mehta MP, Curran WJ Jr. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 2016 Apr 7;374(14):1344-55. link to original article link to PMC article PubMed
- EORTC 22033-26033: Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, Brandes AA, Kantor G, Taphoorn MJ, Hassel MB, Hartmann C, Ryan G, Capper D, Kros JM, Kurscheid S, Wick W, Enting R, Reni M, Thiessen B, Dhermain F, Bromberg JE, Feuvret L, Reijneveld JC, Chinot O, Gijtenbeek JM, Rossiter JP, Dif N, Balana C, Bravo-Marques J, Clement PM, Marosi C, Tzuk-Shina T, Nordal RA, Rees J, Lacombe D, Mason WP, Stupp R. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016 Nov;17(11):1521-1532. Epub 2016 Sep 27. link to original article contains dosing details in abstract link to PMC article PubMed NCT00182819
- ECOG E3F05: NCT00978458
Temozolomide monotherapy
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Baumert et al. 2016 (EORTC 22033-26033) | 2005-2010 | Phase 3 (E-switch-ooc) | Radiotherapy | Did not meet primary endpoint of PFS |
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 21
28-day cycle for up to 12 cycles
References
- EORTC 22033-26033: Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, Brandes AA, Kantor G, Taphoorn MJ, Hassel MB, Hartmann C, Ryan G, Capper D, Kros JM, Kurscheid S, Wick W, Enting R, Reni M, Thiessen B, Dhermain F, Bromberg JE, Feuvret L, Reijneveld JC, Chinot O, Gijtenbeek JM, Rossiter JP, Dif N, Balana C, Bravo-Marques J, Clement PM, Marosi C, Tzuk-Shina T, Nordal RA, Rees J, Lacombe D, Mason WP, Stupp R. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016 Nov;17(11):1521-1532. Epub 2016 Sep 27. link to original article contains dosing details in abstract link to PMC article PubMed NCT00182819
Recurrent or progressive, non-curative therapy
Carboplatin monotherapy
Regimen
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Moghrabi et al. 1998 | NR | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) 560 mg/m2 IV over 60 minutes once on day 1
- Mixed in D5 1/2 NS
Supportive therapy
- Hydration for 1 hour before chemotherapy, and for 1 hour after chemotherapy; total volume including carboplatin is 900 mL/m2
28-day cycle for up to 12 cycles beyond the maximum response
References
- Moghrabi A, Friedman HS, Ashley DM, Bottom KS, Kerby T, Stewart E, Bruggers C, Provenzale JM, Champagne M, Hershon L, Watral M, Ryan J, Rasheed K, Lovell S, Korones D, Fuchs H, George T, McLendon RE, Friedman AH, Buckley E, Longee DC. Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas. Neurosurg Focus. 1998 Apr 15;4(4):e3. link to original article contains dosing details in manuscript PubMed
Carboplatin & Teniposide
Regimen
| Study | Evidence |
|---|---|
| Brandes et al. 2003 | Phase 2 |
Chemotherapy
- Carboplatin (Paraplatin) 350 mg/m2 IV once on day 1
- Teniposide (Vumon) 50 mg/m2 IV once per day on days 1 to 3
Supportive therapy
- Prophylactic 5-HT3 antagonists routinely used
- Lowest dose of corticosteroids necessary to maintain neurologic stability
- Antiepileptic medications for all patients
28-day cycle for up to 10 cycles
References
- Brandes AA, Basso U, Vastola F, Tosoni A, Pasetto LM, Jirillo A, Lonardi S, Paris MK, Koussis H, Monfardini S, Ermani M. Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol. 2003 Dec;14(12):1727-31. link to original article contains dosing details in manuscript PubMed
PCV
PCV: Procarbazine, CCNU (Lomustine), Vincristine
Regimen
| Study | Evidence |
|---|---|
| Brandes et al. 2004 | Phase 2 |
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
Supportive therapy
- Routine use of prophylactic 5-HT3 antagonists
- Steroids given at the lowest dose required by patient's neurologic status
42-day cycle for up to 6 cycles
References
- Brandes AA, Tosoni A, Vastola F, Pasetto LM, Coria B, Danieli D, Iuzzolino P, Gardiman M, Talacchi A, Ermani M. Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy: a phase II study. Cancer. 2004 Nov 1;101(9):2079-85. link to original article contains dosing details in manuscript PubMed
- Retrospective: Triebels VH, Taphoorn MJ, Brandes AA, Menten J, Frenay M, Tosoni A, Kros JM, Stege EB, Enting RH, Allgeier A, van Heuvel I, van den Bent MJ. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas. Neurology. 2004 Sep 14;63(5):904-6. link to original article PubMed
Temozolomide monotherapy
Regimen variant #1, low dose
| Study | Evidence |
|---|---|
| Pouratian et al. 2006 | Retrospective |
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 21
Supportive therapy
- PCP prophylaxis with Trimethoprim/Sulfamethoxazole (Bactrim)
- Antiemetics and stool softeners used as needed
28-day cycle for 12 to 15 cycles
Regimen variant #2, low dose, longer cycles
| Study | Evidence |
|---|---|
| Kesari et al. 2009 | Phase 2 |
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 49
Supportive therapy
- PCP prophylaxis with Trimethoprim/Sulfamethoxazole (Bactrim)
77-day cycle for up to 6 cycles
Regimen variant #3, continuous therapy
| Study | Evidence |
|---|---|
| Perry et al. 2008 (RESCUE) | Phase 2 |
Preceding treatment
- Conventional adjuvant temozolomide, with progression
Regimen variant #4, traditional dosing
| Study | Evidence |
|---|---|
| Chinot et al. 2001 | Phase 2 |
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
28-day cycle for up to 26 cycles (2 years)
References
- Chinot OL, Honore S, Dufour H, Barrie M, Figarella-Branger D, Muracciole X, Braguer D, Martin PM, Grisoli F. Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. J Clin Oncol. 2001 May 1;19(9):2449-55. link to original article contains dosing details in manuscript PubMed
- Retrospective: Pouratian N, Gasco J, Sherman JH, Shaffrey ME, Schiff D. Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas. J Neurooncol. 2007 May;82(3):281-8. Epub 2006 Nov 3. link to original article contains dosing details in manuscript 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 dosing details in manuscript PubMed NCT00392171
- 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 dosing details in manuscript PubMed
- Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, Muzikansky A, Santagata S, Ligon KL, Norden AD, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black PM, Wen PY. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res. 2009 Jan 1;15(1):330-7. link to original article contains dosing details in manuscript PubMed