Low-grade glioma

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Seema Nagpal, MD
Stanford University
Palo Alto, CA

Note: pediatric regimens have been moved to a dedicated page:

7 regimens on this page
10 variants on this page


Guidelines

EANO

NCCN

Adjuvant therapy

PCV

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PCV: Procarbazine, CCNU (Lomustine), Vincristine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Shaw et al. 2012 (RTOG 9802) 1998-2002 Phase III (E-esc) Observation Superior OS1

1Reported efficacy is based on the 2016 update.

Preceding treatment

  • RT x 54 Gy

Chemotherapy

8-week cycle for 6 cycles

References

  1. 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. link to original article contains verified protocol link to PMC article PubMed NCT00003375
    1. 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

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Shaw et al. 2012 (RTOG 9802) 1998-2002 Non-randomized portion of RCT
Baumert et al. 2016 (EORTC 22033-26033) 2005-2010 Phase III (C) Temozolomide Did not meet primary endpoint of PFS

Details here are from RTOG 9802.

Radiotherapy

6-week course

Subsequent treatment

References

  1. 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. link to original article contains verified protocol link to PMC article PubMed NCT00003375
    1. 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
  2. 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. link to original article contains protocol link to PMC article PubMed NCT00182819
  3. ECOG E3F05: NCT00978458

Temozolomide monotherapy

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Baumert et al. 2016 (EORTC 22033-26033) 2005-2010 Phase III (E-switch-ooc) Radiotherapy Did not meet primary endpoint of PFS

Chemotherapy

28-day cycle for up to 12 cycles

References

  1. 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. link to original article contains protocol link to PMC article PubMed NCT00182819

Recurrent or progressive, non-curative therapy

Carboplatin monotherapy

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Regimen

Study Evidence
Moghrabi et al. 1998 Phase II

Chemotherapy

Supportive medications

  • 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

  1. 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 verified protocol PubMed

Carboplatin & Teniposide

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Regimen

Study Evidence
Brandes et al. 2003 Phase II

Chemotherapy

Supportive medications

  • 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

  1. 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 verified protocol PubMed

PCV

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PCV: Procarbazine, CCNU (Lomustine), Vincristine

Regimen

Study Evidence
Brandes et al. 2004 Phase II

Chemotherapy

Supportive medications

42-day cycle for up to 6 cycles

References

  1. 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 verified protocol PubMed
  2. 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

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Regimen variant #1, low dose

Study Evidence
Pouratian et al. 2006 Retrospective

Chemotherapy

Supportive medications

28-day cycle for 12 to 15 cycles

Regimen variant #2, low dose, longer cycles

Study Evidence
Kesari et al. 2009 Phase II

Chemotherapy

Supportive medications

77-day cycle for up to 6 cycles

Regimen variant #3, continuous therapy

Study Evidence
Perry et al. 2008 (RESCUE) Phase II

Preceding treatment

  • Conventional temozolomide, with progression

Chemotherapy

Continued indefinitely

Regimen variant #4, traditional dosing

Study Evidence
Chinot et al. 2001 Phase II

Chemotherapy

28-day cycle for up to 26 cycles (2 years)

References

  1. 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 verified protocol PubMed
  2. 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 verified protocol PubMed
  3. 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
    1. Update: Perry JR, BĂ©langer 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
  4. 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 verified protocol PubMed