Difference between revisions of "Anaplastic glioma"
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− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|neuro}} | |
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''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Anaplastic glioma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br> | ''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Anaplastic glioma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br> | ||
If you are looking for other subtypes of brain cancer, please go to the [[:Category:CNS cancers|'''CNS cancers''']] category page. | If you are looking for other subtypes of brain cancer, please go to the [[:Category:CNS cancers|'''CNS cancers''']] category page. | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
− | |||
=Guidelines= | =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.''' | |
==ASCO/SNO== | ==ASCO/SNO== | ||
− | *'''2022:''' Mohile et al. [https://doi.org/10.1200/jco.21.02036 Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline] | + | *'''2022:''' Mohile et al. [https://doi.org/10.1200/jco.21.02036 Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline] [https://pubmed.ncbi.nlm.nih.gov/34898238/ PubMed] |
==EANO== | ==EANO== | ||
+ | *'''2017:''' [https://doi.org/10.1016/S1470-2045(17)30345-5 European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma (2017)] [https://pubmed.ncbi.nlm.nih.gov/28593859/ PubMed] | ||
− | *''' | + | *'''2014:''' [https://doi.org/10.1016/S1470-2045(14)70011-7 EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma (2014)] [https://pubmed.ncbi.nlm.nih.gov/25079102/ PubMed] |
− | + | ==[https://www.esmo.org/ ESMO]== | |
− | + | *[https://doi.org/10.1093/annonc/mdu050 High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2014)] [https://pubmed.ncbi.nlm.nih.gov/24782454/ PubMed] | |
− | + | ==NCCN== | |
− | ==[ | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425 NCCN Guidelines - Central Nervous System Cancers] and related JNCCN publications below.'' |
− | |||
− | *[ | ||
− | |||
− | == | ||
− | |||
− | *[https://www.nccn.org/ | ||
=Adjuvant therapy= | =Adjuvant therapy= | ||
==Carmustine monotherapy {{#subobject:3918d9|Regimen=1}}== | ==Carmustine monotherapy {{#subobject:3918d9|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:fe64f6|Variant=1}}=== | ===Regimen {{#subobject:fe64f6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/1097-0142(19830915)52:6%3C997::aid-cncr2820520612%3E3.0.co;2-2 Chang et al. 1983] |
|1974-1979 | |1974-1979 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 51: | Line 42: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3171/jns.1985.63.2.0218 Levin et al. 1985 (NCOG 6G61)] |
|1977-1983 | |1977-1983 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 58: | Line 49: | ||
|- | |- | ||
|[https://doi.org/10.1016/0360-3016(95)02025-x Halperin et al. 1996] | |[https://doi.org/10.1016/0360-3016(95)02025-x Halperin et al. 1996] | ||
− | | | + | |1988-11 to 1991-12 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Carmustine_. | + | |[[#Carmustine_.26_Mercaptopurine_999|Carmustine & Mercaptopurine]] |
| style="background-color:#ffffbf" |Did not meet endpoint of OS | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
|- | |- | ||
Line 66: | Line 57: | ||
''<sup>1</sup>Reported efficacy for NCOG 6G61 is based on the 1990 update.''<br> | ''<sup>1</sup>Reported efficacy for NCOG 6G61 is based on the 1990 update.''<br> | ||
''Note: Chang et al. 1983 was technically a negative study, although the subgroup of patients aged 40 to 60 had superior survival in this arm.'' | ''Note: Chang et al. 1983 was technically a negative study, although the subgroup of patients aged 40 to 60 had superior survival in this arm.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *Chang et al. 1983: [[Surgery#CNS_cancer_surgery|Surgery]], then adjuvant [[Regimen_classes#Radiotherapy-based_regimen|RT]] | |
− | *Chang et al. 1983: [[Surgery#CNS_cancer_surgery|Surgery]], then RT | + | *NCOG 6G61: [[Surgery#CNS_cancer_surgery|Surgery]], then adjuvant [[#Hydroxyurea_26_RT_888|Hydrea & WBRT]] |
− | *NCOG 6G61: [[Surgery#CNS_cancer_surgery|Surgery]], then Hydrea & WBRT | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carmustine (BCNU)]] 200 mg/m<sup>2</sup> IV once on day 1 | *[[Carmustine (BCNU)]] 200 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''6-week cycles''' | '''6-week cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Chang CH, Horton J, Schoenfeld D, Salazer O, Perez-Tamayo R, Kramer S, Weinstein A, Nelson JS, Tsukada Y; RTOG; ECOG. Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas: a joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study. Cancer. 1983 Sep 15;52(6):997-1007. [https://doi.org/10.1002/1097-0142(19830915)52:6%3C997::aid-cncr2820520612%3E3.0.co;2-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6349785/ PubMed] | |
− | #Chang CH, Horton J, Schoenfeld D, Salazer O, Perez-Tamayo R, Kramer S, Weinstein A, Nelson JS, Tsukada Y; RTOG; ECOG. Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas: a joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study. Cancer. 1983 Sep 15;52(6):997-1007. [https:// | + | #'''NCOG 6G61:''' Levin VA, Wara WM, Davis RL, Vestnys P, Resser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB. Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas. J Neurosurg. 1985 Aug;63(2):218-23. [https://doi.org/10.3171/jns.1985.63.2.0218 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2991486/ PubMed] |
− | #'''NCOG 6G61:''' Levin VA, Wara WM, Davis RL, Vestnys P, Resser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB. Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas. J Neurosurg. 1985 Aug;63(2):218-23. [ | + | ##'''Update:''' Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4. [https://doi.org/10.1016/0360-3016(90)90096-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2154418/ PubMed] |
− | ##'''Update:''' Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4. [ | + | #Halperin EC, Herndon J, Schold SC, Brown M, Vick N, Cairncross JG, Macdonald DR, Gaspar L, Fischer B, Dropcho E, Rosenfeld S, Morowitz R, Piepmeier J, Hait W, Byrne T, Salter M, Imperato J, Khandekar J, Paleologos N, Burger P, Bentel GC, Friedman A; CNS Cancer Consortium. A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. Int J Radiat Oncol Biol Phys. 1996 Mar 1;34(4):793-802. [https://doi.org/10.1016/0360-3016(95)02025-x link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8598355/ PubMed] |
− | #Halperin EC, Herndon J, Schold SC, Brown M, Vick N, Cairncross JG, Macdonald DR, Gaspar L, Fischer B, Dropcho E, Rosenfeld S, Morowitz R, Piepmeier J, Hait W, Byrne T, Salter M, Imperato J, Khandekar J, Paleologos N, Burger P, Bentel GC, Friedman A; CNS Cancer Consortium. A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. Int J Radiat Oncol Biol Phys. 1996 Mar 1;34(4):793-802. [https://doi.org/10.1016/0360-3016(95)02025-x link to original article] ''' | ||
==PCV {{#subobject:8f71ae|Regimen=1}}== | ==PCV {{#subobject:8f71ae|Regimen=1}}== | ||
− | |||
PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU, '''<u>V</u>'''incristine | PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU, '''<u>V</u>'''incristine | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 60/110/1.4 (capped) {{#subobject:2c6a7b|Variant=1}}=== | ===Regimen variant #1, 60/110/1.4 (capped) {{#subobject:2c6a7b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://aacrjournals.org/clincancerres/article/9/3/981/289131/Phase-III-Randomized-Study-of-Postradiotherapy Levin et al. 2003] |
|1992-1999 | |1992-1999 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#PCV_. | + | |[[#PCV_.26_DMFO_999|PCV & DMFO]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup> | ||
|- | |- | ||
Line 105: | Line 94: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[Anaplastic_glioma_-_null_regimens#Observation|No further treatment]] | |[[Anaplastic_glioma_-_null_regimens#Observation|No further treatment]] | ||
− | | style="background-color:# | + | | style="background-color:#91cf60" |Seems to have superior OS<sup>2</sup> (primary endpoint)<br>Median OS: 3.5 vs 2.6 y<br>(HR 0.78, 95% CI 0.63-0.98) |
|- | |- | ||
|} | |} | ||
''<sup>1</sup>Levin et al. 2003 had a complex hazard function; see paper for details.''<br> | ''<sup>1</sup>Levin et al. 2003 had a complex hazard function; see paper for details.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for EORTC 26951 is based on the 2022 update.''<br> | ||
''Chemotherapy begins within 4 weeks after completion of radiation therapy:'' | ''Chemotherapy begins within 4 weeks after completion of radiation therapy:'' | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*[[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deletion:]] As of WHO 2016 IDH mutated, [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors are classified as oligodendroglioma | *[[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deletion:]] As of WHO 2016 IDH mutated, [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors are classified as oligodendroglioma | ||
− | |||
* [https://pubmed.ncbi.nlm.nih.gov/23071237 EORTC 26951]: van den Bent et al. 2013 noted that [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors received the more benefit from adjuvant PCV as compared to tumors without 1p/19q co-deletion. | * [https://pubmed.ncbi.nlm.nih.gov/23071237 EORTC 26951]: van den Bent et al. 2013 noted that [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors received the more benefit from adjuvant PCV as compared to tumors without 1p/19q co-deletion. | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[Surgery#CNS_cancer_surgery|Surgery]], then adjuvant [[#Radiation_therapy|RT]] x 4500 cGy with 1440 cGy boost | |
− | *[[Surgery#CNS_cancer_surgery|Surgery]], then [[#Radiation_therapy|RT]] x | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8 & 29 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *Antiemetics for lomustine: "[[Domperidone (Motilium)]] or [[Metoclopramide (Reglan)]], and if necessary, [[Ondansetron (Zofran)]] or a similar agent" |
− | |||
− | *Antiemetics for | ||
*[[:Category:Steroids|Corticosteroids]] kept at lowest possible dose | *[[:Category:Steroids|Corticosteroids]] kept at lowest possible dose | ||
− | |||
'''42-day cycle for 6 cycles (EORTC 26951) or 7 cycles (Levin et al. 2003)''' | '''42-day cycle for 6 cycles (EORTC 26951) or 7 cycles (Levin et al. 2003)''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 60/110/1.4 (no cap) {{#subobject:f52744|Variant=1}}=== | ===Regimen variant #2, 60/110/1.4 (no cap) {{#subobject:f52744|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.3171/jns.1985.63.2.0218 Levin et al. 1985 (NCOG 6G61)] |
|1977-1983 | |1977-1983 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 150: | Line 137: | ||
''<sup>1</sup>Reported efficacy is based on the 1990 update.''<br> | ''<sup>1</sup>Reported efficacy is based on the 1990 update.''<br> | ||
''Note: the total number of cycles is not specified in this protocol.'' | ''Note: the total number of cycles is not specified in this protocol.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[Surgery#CNS_cancer_surgery|Surgery]], then adjuvant [[#Hydroxyurea_26_RT_888|Hydrea & WBRT]] | |
− | *[[Surgery#CNS_cancer_surgery|Surgery]], then Hydrea & WBRT | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 8 & 29 | ||
− | |||
'''6- to 8-week cycles''' | '''6- to 8-week cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 60/110/2 x 4 {{#subobject:300971|Variant=1}}=== | ===Regimen variant #3, 60/110/2 x 4 {{#subobject:300971|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 180: | Line 167: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 2 mg IV once per day on days 8 & 29 | ||
− | |||
'''8-week cycle for 4 cycles''' | '''8-week cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *NOA-04, patients with stable disease or better: [[#PCV|PCV]] continuation x 2 (6 total) | |
− | * | + | *NOA-04, at time of disease progression: Salvage [[#Radiation_therapy_2|RT]] |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #4, 75/130/1.4 (no cap) x 4 {{#subobject:42a14f|Variant=1}}=== | ===Regimen variant #4, 75/130/1.4 (no cap) x 4 {{#subobject:42a14f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0360-3016(99)00265-5 Prados et al. 1999 (RTOG 9404)] |
|1991-1997 | |1991-1997 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#PCV_. | + | |[[#PCV_.26_BUdR_999|PCV & BUdR]] |
− | | style="background-color:#ffffbf" |Did not meet primary endpoints of TTP/OS | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of TTP/OS |
|- | |- | ||
|[https://doi.org/10.1200/JCO.2005.04.3414 Cairncross et al. 2006 (RTOG 9402)] | |[https://doi.org/10.1200/JCO.2005.04.3414 Cairncross et al. 2006 (RTOG 9402)] | ||
Line 214: | Line 202: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[Anaplastic_glioma_-_null_regimens#Observation|No chemotherapy]] | |[[Anaplastic_glioma_-_null_regimens#Observation|No chemotherapy]] | ||
− | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> | + | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 4.8 vs 4.8 y<br>(HR 0.79, 95% CI 0.61-1.03) |
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup>Reported efficacy for RTOG 9402 is based on the | + | ''<sup>1</sup>Reported efficacy for RTOG 9402 is based on the 2022 update.''<br> |
''Note: the abstract of Prados et al. 2004 does not have dosing details.'' | ''Note: the abstract of Prados et al. 2004 does not have dosing details.'' | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*[[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deletion:]] As of WHO 2016 IDH mutated, [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors are classified as oligodendroglioma | *[[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deletion:]] As of WHO 2016 IDH mutated, [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors are classified as oligodendroglioma | ||
− | |||
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732012/ RTOG 9402]: a survival benefit was noted in the population with [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors | * [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732012/ RTOG 9402]: a survival benefit was noted in the population with [[Biomarkers#Chromosomal regions#1p19q|1p/19q co-deleted]] tumors | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 75 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 75 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 130 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 130 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 8 & 29 | ||
− | |||
'''6-week cycle for 4 cycles''' | '''6-week cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *Adjuvant [[#Radiation_therapy|RT]] x 5040 cGy + 900 cGy boost | |
− | *[[#Radiation_therapy|RT]] x | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #5, 100/100/1.5 (capped) x 12 {{#subobject:3dc3c8|Variant=1}}=== | ===Regimen variant #5, 100/100/1.5 (capped) x 12 {{#subobject:3dc3c8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 256: | Line 245: | ||
|} | |} | ||
''Chemotherapy begins 3 to 4 weeks after completion of radiation therapy.'' | ''Chemotherapy begins 3 to 4 weeks after completion of radiation therapy.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[Surgery#CNS_cancer_surgery|Surgery]], then adjuvant [[#Radiation_therapy|RT]] x 4500 cGy or [[#Radiation_therapy|RT]] x 6000 cGy | |
− | *[[Surgery#CNS_cancer_surgery|Surgery]], then [[#Radiation_therapy|RT]] x | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 10 | *[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 10 | ||
*[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*[[:Category:Steroids|Corticosteroid]] use was left up to physician discretion. It was recommended to not discontinue steroids until at least 6 weeks after radiation therapy. If it was to be discontinued, it should be tapered down gradually over several weeks, or could be titrated down to the lowest tolerated dose. | *[[:Category:Steroids|Corticosteroid]] use was left up to physician discretion. It was recommended to not discontinue steroids until at least 6 weeks after radiation therapy. If it was to be discontinued, it should be tapered down gradually over several weeks, or could be titrated down to the lowest tolerated dose. | ||
− | |||
'''42-day cycle for up to 12 cycles''' | '''42-day cycle for up to 12 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''NCOG 6G61:''' Levin VA, Wara WM, Davis RL, Vestnys P, Resser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB. Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas. J Neurosurg. 1985 Aug;63(2):218-23. [https://doi.org/10.3171/jns.1985.63.2.0218 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2991486/ PubMed] | |
− | #'''NCOG 6G61:''' Levin VA, Wara WM, Davis RL, Vestnys P, Resser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB. Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas. J Neurosurg. 1985 Aug;63(2):218-23. [ | + | ##'''Update:''' Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4. [https://doi.org/10.1016/0360-3016(90)90096-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2154418/ PubMed] |
− | ##'''Update:''' Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4. [ | + | #'''MRC BR05:''' Thomas D, Brada M, Stenning S; Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001 Jan 15;19(2):509-18. [https://doi.org/10.1200/jco.2001.19.2.509 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11208845/ PubMed] |
− | #'''MRC BR05:''' Thomas D, Brada M, Stenning S; Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001 Jan 15;19(2):509-18. [https://doi.org/10.1200/jco.2001.19.2.509 link to original article] ''' | + | #Levin VA, Hess KR, Choucair A, Flynn PJ, Jaeckle KA, Kyritsis AP, Yung WK, Prados MD, Bruner JM, Ictech S, Gleason MJ, Kim HW. Phase III randomized study of postradiotherapy chemotherapy with combination alpha-difluoromethylornithine-PCV versus PCV for anaplastic gliomas. Clin Cancer Res. 2003 Mar;9(3):981-90. [https://aacrjournals.org/clincancerres/article/9/3/981/289131/Phase-III-Randomized-Study-of-Postradiotherapy link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12631596/ PubMed] |
− | #Levin VA, Hess KR, Choucair A, Flynn PJ, Jaeckle KA, Kyritsis AP, Yung WK, Prados MD, Bruner JM, Ictech S, Gleason MJ, Kim HW. Phase III randomized study of postradiotherapy chemotherapy with combination alpha-difluoromethylornithine-PCV versus PCV for anaplastic gliomas. Clin Cancer Res. 2003 Mar;9(3):981-90. [ | + | #'''RTOG 9404:''' Prados MD, Scott C, Sandler H, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404. Int J Radiat Oncol Biol Phys. 1999 Dec 1;45(5):1109-15. [https://doi.org/10.1016/S0360-3016(99)00265-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10613302/ PubMed] |
− | #'''RTOG 9404:''' Prados MD, Scott C, Sandler H, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404. Int J Radiat Oncol Biol Phys. 1999 Dec 1;45(5):1109-15. [https:// | + | ##'''Update:''' Prados MD, Seiferheld W, Sandler HM, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. Int J Radiat Oncol Biol Phys. 2004 Mar 15;58(4):1147-52. [https://doi.org/10.1016/j.ijrobp.2003.08.024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15001257/ PubMed] |
− | ##'''Update:''' Prados MD, Seiferheld W, Sandler HM, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. Int J Radiat Oncol Biol Phys. 2004 Mar 15;58(4):1147-52. [https:// | + | #'''RTOG 9402:''' Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. [https://doi.org/10.1200/JCO.2005.04.3414 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782910/ PubMed] [https://clinicaltrials.gov/study/NCT00002569 NCT00002569] |
− | #'''RTOG 9402:''' Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. [https://doi.org/10.1200/JCO.2005.04.3414 link to original article] ''' | + | ##'''Update:''' Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. Epub 2012 Oct 15. [https://doi.org/10.1200/JCO.2012.43.2674 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23071247/ PubMed] |
− | ##'''Update:''' Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. Epub 2012 Oct 15. [https://doi.org/10.1200/JCO.2012.43.2674 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23071247 PubMed] | + | ##'''Pooled update:''' Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. [https://doi.org/10.1200/jco.21.02543 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362869/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35731991/ PubMed] |
− | #''' | + | #'''EORTC 26951:''' van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006 Jun 20;24(18):2715-22. [https://doi.org/10.1200/jco.2005.04.6078 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782911/ PubMed] [https://clinicaltrials.gov/study/NCT00002840 NCT00002840] |
− | + | ##'''Update:''' van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013 Jan 20;31(3):344-50. Epub 2012 Oct 15. [https://doi.org/10.1200/jco.2012.43.2229 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23071237/ PubMed] | |
− | + | ##'''Pooled update:''' Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. [https://doi.org/10.1200/jco.21.02543 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362869/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35731991/ PubMed] | |
− | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https:// | + | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19901110/ PubMed] [https://clinicaltrials.gov/study/NCT00717210 NCT00717210] |
+ | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https://doi.org/10.1093/neuonc/now133 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27370396/ PubMed] | ||
==Radiation therapy {{#subobject:d181ec|Regimen=1}}== | ==Radiation therapy {{#subobject:d181ec|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 4500 cGy {{#subobject:47e004|Variant=1}}=== | |
− | ===Regimen variant #1, | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 301: | Line 287: | ||
|1983-1988 | |1983-1988 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Radiation_therapy|RT]] x | + | |[[#Radiation_therapy|RT]] x 6000 cGy |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2001.19.2.509 Thomas et al. 2001 (MRC BR05)] | |[https://doi.org/10.1200/jco.2001.19.2.509 Thomas et al. 2001 (MRC BR05)] | ||
|1988-1997 | |1988-1997 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
Line 312: | Line 298: | ||
|} | |} | ||
''Radiation therapy starts preferably within 3, but no more than 6, weeks after neurosurgery.'' | ''Radiation therapy starts preferably within 3, but no more than 6, weeks after neurosurgery.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy]] 225 cGy fractions x 20 fractions (total dose of 4500 cGy) | |
− | *[[External beam radiotherapy]] | ||
− | |||
'''4-week course''' | '''4-week course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
+ | *MRC BR05: Adjuvant [[#PCV|PCV]] versus [[Anaplastic_glioma_-_null_regimens#Observation|no further treatment]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | + | ===Regimen variant #2, 4500 cGy with 1440 cGy boost {{#subobject:75fc7d|Variant=1}}=== | |
− | |||
− | ===Regimen variant #2, | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2005.04.6078 van den Bent et al. 2006 (EORTC 26951)] | |[https://doi.org/10.1200/jco.2005.04.6078 van den Bent et al. 2006 (EORTC 26951)] | ||
|1996-2002 | |1996-2002 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
|- | |- | ||
|} | |} | ||
''Radiation therapy starts within 6 weeks after surgery.'' | ''Radiation therapy starts within 6 weeks after surgery.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy]], 180 cGy fractions x 25 fractions, total dose of 4500 cGy to the planning target volume (PTV-1); then a boost of 180 cGy fractions x 8 fractions, total boost dose of 1440 cGy to the PTV-2, for a total cumulative dose of 5940 cGy | |
− | *[[External beam radiotherapy]], | ||
− | |||
'''6.5-week course''' | '''6.5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *Adjuvant [[#PCV|PCV]] versus [[Anaplastic_glioma_-_null_regimens#Observation|no further treatment]] | |
− | *[[#PCV|PCV]] versus [[Anaplastic_glioma_-_null_regimens#Observation|no further treatment]] | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen variant #3, | + | ===Regimen variant #3, 5040 cGy with 900 cGy boost {{#subobject:4637d3|Variant=1}}=== |
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/JCO.2005.04.3414 Cairncross et al. 2006 (RTOG 9402)] | |[https://doi.org/10.1200/JCO.2005.04.3414 Cairncross et al. 2006 (RTOG 9402)] | ||
|1994-2002 | |1994-2002 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
|- | |- | ||
|} | |} | ||
''Radiation therapy starts within 6 weeks after surgery or chemotherapy.'' | ''Radiation therapy starts within 6 weeks after surgery or chemotherapy.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[Surgery#CNS_cancer_surgery|Surgery]] versus [[#PCV|PCV]] induction x 6 | |
− | *[[Surgery#CNS_cancer_surgery|Surgery]] versus [[#PCV|PCV]] x 6 | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy]], 180 cGy fractions x 28 fractions, total dose of 5040 cGy to the planning target volume (PTV-1); then a boost of 180 cGy fractions x 5 fractions, total boost dose of 900 cGy to the PTV-2, for a total cumulative dose of 5940 cGy | |
− | *[[External beam radiotherapy]], | ||
− | |||
'''6.5-week course''' | '''6.5-week course''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant #4, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #4, 6000 cGy {{#subobject:327fcb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 384: | Line 372: | ||
|1983-1988 | |1983-1988 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[#Radiation_therapy|RT]] x | + | |[[#Radiation_therapy|RT]] x 4500 cGy |
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
Line 393: | Line 381: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS24 | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS24 | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.ejca.2007.12.005 Hildebrand et al. 2008 (EORTC 26882)] |
|1988-2000 | |1988-2000 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Carmustine.2C_DBD. | + | |[[#Carmustine.2C_DBD.2C_RT_999|BCNU, DBD, RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2005.04.6078 van den Bent et al. 2006 (EORTC 26951)] | |[https://doi.org/10.1200/jco.2005.04.6078 van den Bent et al. 2006 (EORTC 26951)] | ||
|1996-2002 | |1996-2002 | ||
− | | style="background-color:# | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
− | | | + | | style="background-color:#d3d3d3" | |
− | | style="background-color:# | + | | style="background-color:#d3d3d3" | |
|- | |- | ||
| rowspan="2" |[https://doi.org/10.1200/jco.2009.23.6497 Wick et al. 2009 (NOA-04)] | | rowspan="2" |[https://doi.org/10.1200/jco.2009.23.6497 Wick et al. 2009 (NOA-04)] | ||
Line 416: | Line 404: | ||
|} | |} | ||
''Note: dosing details are not described in the abstract of Hildebrand et al. 2008.'' | ''Note: dosing details are not described in the abstract of Hildebrand et al. 2008.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy]] with 180 to 200 cGy fractions for a total dose of 6000 cGy | |
− | *[[External beam radiotherapy]] with | ||
− | |||
'''6-week course''' | '''6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *MRC BR05 & EORTC 26951: Adjuvant [[#PCV|PCV]] versus [[Anaplastic_glioma_-_null_regimens#Observation|no further treatment]] | |
− | *MRC BR05: [[#PCV|PCV]] versus [[Anaplastic_glioma_-_null_regimens#Observation|no further treatment]] | + | *NOA-04, upon progression: Salvage [[#PCV_2|PCV]] versus [[#Temozolomide_monotherapy_2|temozolomide]] |
− | *NOA-04, upon progression: [[#PCV_2|PCV]] versus [[#Temozolomide_monotherapy_2|temozolomide]] | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''MRC BR02:''' Bleehen NM, Stenning SP; Medical Research Council Brain Tumour Working Party. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer. 1991 Oct;64(4):769-74. [https://doi.org/10.1038/bjc.1991.396 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977696/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/1654987/ PubMed] | |
− | #'''MRC BR02:''' Bleehen NM, Stenning SP; Medical Research Council Brain Tumour Working Party. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer. 1991 Oct;64(4):769-74. [https://doi.org/10.1038/bjc.1991.396 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977696/ link to PMC article] ''' | + | #'''MRC BR05:''' Thomas D, Brada M, Stenning S; Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001 Jan 15;19(2):509-18. [https://doi.org/10.1200/jco.2001.19.2.509 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11208845/ PubMed] |
− | #'''MRC BR05:''' Thomas D, Brada M, Stenning S; Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001 Jan 15;19(2):509-18. [https://doi.org/10.1200/jco.2001.19.2.509 link to original article] ''' | + | #'''RTOG 9402:''' Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. [https://doi.org/10.1200/JCO.2005.04.3414 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782910/ PubMed] [https://clinicaltrials.gov/study/NCT00002569 NCT00002569] |
− | #'''RTOG 9402:''' Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. [https://doi.org/10.1200/JCO.2005.04.3414 link to original article] ''' | + | ##'''Update:''' Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. Epub 2012 Oct 15. [https://doi.org/10.1200/JCO.2012.43.2674 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23071247/ PubMed] |
− | ##'''Update:''' Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. Epub 2012 Oct 15. [https://doi.org/10.1200/JCO.2012.43.2674 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732012/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23071247 PubMed] | + | ##'''Pooled update:''' Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. [https://doi.org/10.1200/jco.21.02543 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362869/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35731991/ PubMed] |
− | #''' | + | #'''EORTC 26951:''' van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006 Jun 20;24(18):2715-22. [https://doi.org/10.1200/jco.2005.04.6078 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16782911/ PubMed] [https://clinicaltrials.gov/study/NCT00002840 NCT00002840] |
− | + | ##'''Update:''' van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013 Jan 20;31(3):344-50. Epub 2012 Oct 15. [https://doi.org/10.1200/jco.2012.43.2229 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23071237/ PubMed] | |
− | #''' | + | ##'''Pooled update:''' Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. [https://doi.org/10.1200/jco.21.02543 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362869/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35731991/ PubMed] |
− | #''' | + | #'''EORTC 26882:''' Hildebrand J, Gorlia T, Kros JM, Afra D, Frenay M, Omuro A, Stupp R, Lacombe D, Allgeier A, van den Bent MJ; [[Study_Groups#EORTC|EORTC]] Brain Tumour Group. Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882). Eur J Cancer. 2008 Jun;44(9):1210-6. Epub 2008 Jan 14. [https://doi.org/10.1016/j.ejca.2007.12.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18248979/ PubMed] [https://clinicaltrials.gov/study/NCT00002620 NCT00002620] |
− | + | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19901110/ PubMed] [https://clinicaltrials.gov/study/NCT00717210 NCT00717210] | |
− | #'''NOA- | + | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https://doi.org/10.1093/neuonc/now133 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27370396/ PubMed] |
− | + | #'''NOA-08:''' Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; Neuro-oncology Working Group of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. Epub 2012 May 10. [https://doi.org/10.1016/S1470-2045(12)70164-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22578793/ PubMed] [https://clinicaltrials.gov/study/NCT01502241 NCT01502241] | |
==RT, then Carmustine {{#subobject:507405|Regimen=1}}== | ==RT, then Carmustine {{#subobject:507405|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen {{#subobject:31c739|Variant=1}}=== | + | ===Regimen variant #1, WBRT {{#subobject:31c739|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | | rowspan="2" |[https://doi.org/10.3171/jns.1989.71.1.0001 Shapiro et al. 1989 (BTCG 8001)] | ||
+ | |rowspan=2|1980-1983 | ||
+ | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1. [[#Carmustine.2FProcarbazine_.26_RT_999|Carmustine/Procarbazine & RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |2. [[#Carmustine_.26_Hydrea.2FProcarbazine.2C_VM-26.2C_RT_999|Carmustine & Hydrea/Procarbazine, VM-26, RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Pulmonary function tests (PFTs) were checked before start of therapy, and then when cumulative dose of [[Carmustine (BCNU)]] reaches 800 mg/m<sup>2</sup> and 1200 mg/m<sup>2</sup>.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#CNS_cancer_surgery|Surgery]], within 3 weeks | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Radiotherapy==== | ||
+ | *Whole-brain [[External beam radiotherapy]], 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets) | ||
+ | '''7-week course, followed by:''' | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carmustine (BCNU)]] 80 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 3 | ||
+ | '''8-week cycle for up to 18 cycles (a maximum cumulative carmustine dose of 1500 mg/m<sup>2</sup>)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, WBRT with cone-down {{#subobject:31c739|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | | rowspan="2" |[ | + | | rowspan="2" |[https://doi.org/10.3171/jns.1989.71.1.0001 Shapiro et al. 1989 (BTCG 8001)] |
|rowspan=2|1980-1983 | |rowspan=2|1980-1983 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | ||
− | |1. [[#Carmustine.2FProcarbazine_. | + | |1. [[#Carmustine.2FProcarbazine_.26_RT_999|Carmustine/Procarbazine & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |2. [[#Carmustine_.26_Hydrea.2FProcarbazine.2C_VM-26. | + | |2. [[#Carmustine_.26_Hydrea.2FProcarbazine.2C_VM-26.2C_RT_999|Carmustine & Hydrea/Procarbazine, VM-26, RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: Pulmonary function tests (PFTs) were checked before start of therapy, and then when cumulative dose of [[Carmustine (BCNU)]] reaches 800 mg/m<sup>2</sup> and 1200 mg/m<sup>2</sup>.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[Surgery#CNS_cancer_surgery|Surgery]], within 3 weeks | |
− | *[[Surgery#CNS_cancer_surgery|Surgery]] | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Whole-brain [[External beam radiotherapy]], 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) | |
− | *[[External beam radiotherapy]] | + | '''7-week course, followed by:''' |
− | |||
− | |||
− | |||
− | ''' | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carmustine (BCNU)]] 80 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 3 | *[[Carmustine (BCNU)]] 80 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 3 | ||
− | + | '''8-week cycle for up to 18 cycles (a maximum cumulative carmustine dose of 1500 mg/m<sup>2</sup>)''' | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | '''8-week cycles | ||
− | |||
===References=== | ===References=== | ||
− | + | #'''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. [https://doi.org/10.3171/jns.1989.71.1.0001 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/2661738/ 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. [ | ||
==RT, then Temozolomide {{#subobject:48949a|Regimen=1}}== | ==RT, then Temozolomide {{#subobject:48949a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:a96d3d|Variant=1}}=== | ===Regimen {{#subobject:a96d3d|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 501: | Line 511: | ||
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ van den Bent et al. 2017 (CATNON)] | | rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ van den Bent et al. 2017 (CATNON)] | ||
|rowspan=2|2007-2015 | |rowspan=2|2007-2015 | ||
− | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
− | |1. [[#Radiation_therapy|RT]]<br> 2. [[#Temozolomide_.26_RT|Temozolomide & RT]] | + | |1. [[#Radiation_therapy|RT]]<br>2. [[#Temozolomide_.26_RT|Temozolomide & RT]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>OS60: 55.9% vs 44.1%<br>(HR 0.65, 99.145% CI 0.45-0.93) |
|- | |- | ||
|3. [[#Temozolomide_.26_RT.2C_then_Temozolomide|Temozolomide & RT, then Temozolomide]] | |3. [[#Temozolomide_.26_RT.2C_then_Temozolomide|Temozolomide & RT, then Temozolomide]] | ||
Line 509: | Line 519: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
This study excluded patients with [[Biomarkers#Chromosomal regions#1p19q|1p19q codeletions]]. As of WHO 2016 [[Biomarkers#genes|IDH mutated]], [[Biomarkers#Chromosomal regions#1p19q|1p19q co-deleted]] tumors are classified as oligodendroglioma . This study is of Anaplastic Astrocytoma and included patients with both [[Biomarkers#genes|IDH mutant]] and IDH wild-type astrocytomas. | This study excluded patients with [[Biomarkers#Chromosomal regions#1p19q|1p19q codeletions]]. As of WHO 2016 [[Biomarkers#genes|IDH mutated]], [[Biomarkers#Chromosomal regions#1p19q|1p19q co-deleted]] tumors are classified as oligodendroglioma . This study is of Anaplastic Astrocytoma and included patients with both [[Biomarkers#genes|IDH mutant]] and IDH wild-type astrocytomas. | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy]] as follows: | |
− | *[[External beam radiotherapy]] 1 | + | **Cycle 1: 180 cGy x 33 fractions (total dose of 5940 cGy) |
− | |||
− | |||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] as follows: | *[[Temozolomide (Temodar)]] as follows: | ||
− | **Cycle | + | **Cycle 2: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | **Cycles | + | **Cycles 3 to 13: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | + | '''11-week course, then 28-day cycle for 12 cycles''' | |
− | '''28-day cycle for 12 cycles''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''CATNON:''' van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; [[Study_Groups#EORTC|EORTC]]. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. [https://doi.org/10.1016/S0140-6736(17)31442-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28801186/ PubMed] [https://clinicaltrials.gov/study/NCT00626990 NCT00626990] | |
− | #'''CATNON:''' van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; [[Study_Groups#EORTC|EORTC]]. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. [https:// | ||
==Temozolomide monotherapy {{#subobject:3d22d3|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:3d22d3|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 100 mg/m<sup>2</sup>, 7 out of 14 days {{#subobject:762df5|Variant=1}}=== | ===Regimen variant #1, 100 mg/m<sup>2</sup>, 7 out of 14 days {{#subobject:762df5|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70164-X Wick et al. 2012 (NOA-08)] |
− | |2005-2009 | + | |2005-05-15 to 2009-11-02 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Radiation_therapy|Radiation therapy]] | |[[#Radiation_therapy|Radiation therapy]] | ||
− | | style="background-color:#eeee01" |Seems to have non-inferior OS | + | | style="background-color:#eeee01" |Seems to have non-inferior OS (primary endpoint)<br>Median OS: 8.6 vs 9.6 mo<br>(HR 1.09, 95% CI 0.84-1.42) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 7 | *[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 7 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 200 mg/m<sup>2</sup>, 5 out of 28 days x 8 cycles {{#subobject:5bc6bc|Variant=1}}=== | ===Regimen variant #2, 200 mg/m<sup>2</sup>, 5 out of 28 days x 8 cycles {{#subobject:5bc6bc|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 580: | Line 585: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | |||
'''28-day cycle for 8 cycles''' | '''28-day cycle for 8 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *NOA-04, SD or better: [[#Temozolomide_monotherapy|Temozolomide]] continuation x 4 (12 total) | |
− | *SD or better: [[#Temozolomide_monotherapy|Temozolomide]] x 4 (12 total) | + | *NOA-04, upon progression: Salvage [[#Radiation_therapy_2|RT]] |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #3, 200 mg/m<sup>2</sup>, 5 out of 28 days x 2y {{#subobject:f096ab|Variant=1}}=== | ===Regimen variant #3, 200 mg/m<sup>2</sup>, 5 out of 28 days x 2y {{#subobject:f096ab|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1007/s11060-005-9020-1 Taliansky-Aronov et al. 2006] | |[https://doi.org/10.1007/s11060-005-9020-1 Taliansky-Aronov et al. 2006] | ||
+ | |Not reported | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*[[:Category:Steroids|Corticosteroids]] could be continued at same dose or reduced, but not increased while on study | *[[:Category:Steroids|Corticosteroids]] could be continued at same dose or reduced, but not increased while on study | ||
− | |||
'''28-day cycle for up to 26 cycles (2 years)''' | '''28-day cycle for up to 26 cycles (2 years)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 5 out of 28 days, with dose-escalation, indefinite {{#subobject:f5f4a1|Variant=1}}=== | ===Regimen variant #4, 5 out of 28 days, with dose-escalation, indefinite {{#subobject:f5f4a1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1007/s11060-008-9735-x Mikkelsen et al. 2009] | |[https://doi.org/10.1007/s11060-008-9735-x Mikkelsen et al. 2009] | ||
+ | |Not reported | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*[[Biomarkers|1p/19q]] loss of heterozygosity (LOH) | *[[Biomarkers|1p/19q]] loss of heterozygosity (LOH) | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] as follows: | *[[Temozolomide (Temodar)]] as follows: | ||
− | **Cycles 1 & 2: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, on empty stomach | + | **Cycles 1 & 2: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | **Cycle 3 onwards (if no myelosuppression): 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, on empty stomach | + | **Cycle 3 onwards (if no myelosuppression): 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol. 2006 Sep;79(2):153-7. Epub 2006 Jul 20. [https://doi.org/10.1007/s11060-005-9020-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16855865/ PubMed] | |
− | #Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol. 2006 Sep;79(2):153-7. Epub 2006 Jul 20. [https://doi.org/10.1007/s11060-005-9020-1 link to original article] ''' | + | #Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol. 2009 Mar;92(1):57-63. Epub 2008 Nov 15. [https://doi.org/10.1007/s11060-008-9735-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19011763/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | #Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol. 2009 Mar;92(1):57-63. Epub 2008 Nov 15. [https://doi.org/10.1007/s11060-008-9735-x link to original article] ''' | + | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19901110/ PubMed] [https://clinicaltrials.gov/study/NCT00717210 NCT00717210] |
− | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] ''' | + | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https://doi.org/10.1093/neuonc/now133 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27370396/ PubMed] |
− | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https:// | + | #'''NOA-08:''' Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; Neuro-oncology Working Group of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. Epub 2012 May 10. [https://doi.org/10.1016/S1470-2045(12)70164-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22578793/ PubMed] [https://clinicaltrials.gov/study/NCT01502241 NCT01502241] |
− | #'''NOA-08:''' Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; Neuro-oncology Working Group of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. [https:// | ||
==Temozolomide, then Temozolomide & RT, then Temozolomide {{#subobject:086841|Regimen=1}}== | ==Temozolomide, then Temozolomide & RT, then Temozolomide {{#subobject:086841|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Protocol {{#subobject:eb5d94|Variant=1}}=== | ===Protocol {{#subobject:eb5d94|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1007/s11060-008-9735-x Mikkelsen et al. 2009] | |[https://doi.org/10.1007/s11060-008-9735-x Mikkelsen et al. 2009] | ||
+ | |Not reported | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*This protocol is meant for patients without [[Biomarkers|1p/19q]] loss of heterozygosity (LOH). | *This protocol is meant for patients without [[Biomarkers|1p/19q]] loss of heterozygosity (LOH). | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
− | ====Chemotherapy, | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy, pre-radiation portion==== | |
*[[Temozolomide (Temodar)]] as follows: | *[[Temozolomide (Temodar)]] as follows: | ||
− | **Cycles 1 & 2: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, on empty stomach | + | **Cycles 1 & 2: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | ** | + | **Cycles 3 & 4 (if no myelosuppression): 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | |||
'''28-day cycle for 2 to 4 cycles, followed by:''' | '''28-day cycle for 2 to 4 cycles, followed by:''' | ||
− | + | ====Chemotherapy, concurrent radiation portion==== | |
− | ====Chemotherapy, | ||
− | |||
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day during radiation therapy | *[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day during radiation therapy | ||
− | + | ====Radiotherapy, concurrent radiation portion==== | |
− | ====Radiotherapy==== | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: a total dose of 6000 cGy |
− | |||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | ||
− | |||
'''One course, followed by:''' | '''One course, followed by:''' | ||
− | + | ====Chemotherapy, maintenance portion==== | |
− | ====Chemotherapy, | + | *[[Temozolomide (Temodar)]] 150 to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach |
− | |||
− | *[[Temozolomide (Temodar)]] 150 to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, on empty stomach | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol. 2009 Mar;92(1):57-63. Epub 2008 Nov 15. [https://doi.org/10.1007/s11060-008-9735-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19011763/ PubMed] content property of [https://hemonc.org HemOnc.org] | |
− | #Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol. 2009 Mar;92(1):57-63. Epub 2008 Nov 15. [https://doi.org/10.1007/s11060-008-9735-x link to original article] ''' | ||
==Temozolomide & RT {{#subobject:bca8f6|Regimen=1}}== | ==Temozolomide & RT {{#subobject:bca8f6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:57a301|Variant=1}}=== | ===Regimen {{#subobject:57a301|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 706: | Line 709: | ||
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ van den Bent et al. 2017 (CATNON)] | | rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ van den Bent et al. 2017 (CATNON)] | ||
|rowspan=2|2007-2015 | |rowspan=2|2007-2015 | ||
− | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
|1. [[#Radiation_therapy|RT]] | |1. [[#Radiation_therapy|RT]] | ||
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
|2. [[#Temozolomide_.26_RT.2C_then_Temozolomide|Temozolomide & RT, then Temozolomide]]<br> 3. [[#RT.2C_then_Temozolomide|RT, then Temozolomide]] | |2. [[#Temozolomide_.26_RT.2C_then_Temozolomide|Temozolomide & RT, then Temozolomide]]<br> 3. [[#RT.2C_then_Temozolomide|RT, then Temozolomide]] | ||
− | | style="background-color:#d73027" |Inferior OS | + | | style="background-color:#d73027" |Inferior OS (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
This study excluded patients with [[Biomarkers#Chromosomal regions#1p19q|1p19q codeletions]]. As of WHO 2016 [[Biomarkers#genes|IDH mutated]], [[Biomarkers#Chromosomal regions#1p19q|1p19q co-deleted]] tumors are classified as oligodendroglioma. This study is of Anaplastic Astrocytoma and included patients with both [[Biomarkers#genes|IDH mutant]] and IDH wild-type astrocytomas. | This study excluded patients with [[Biomarkers#Chromosomal regions#1p19q|1p19q codeletions]]. As of WHO 2016 [[Biomarkers#genes|IDH mutated]], [[Biomarkers#Chromosomal regions#1p19q|1p19q co-deleted]] tumors are classified as oligodendroglioma. This study is of Anaplastic Astrocytoma and included patients with both [[Biomarkers#genes|IDH mutant]] and IDH wild-type astrocytomas. | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 45 | |
− | *[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day | ||
− | |||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45 (33 fractions; total dose of 5940 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 1 | + | '''45-day course''' |
− | + | </div></div> | |
− | ''' | ||
− | |||
===References=== | ===References=== | ||
− | + | #'''CATNON:''' van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; [[Study_Groups#EORTC|EORTC]]. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. [https://doi.org/10.1016/S0140-6736(17)31442-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28801186/ PubMed] [https://clinicaltrials.gov/study/NCT00626990 NCT00626990] | |
− | #'''CATNON:''' van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; [[Study_Groups#EORTC|EORTC]]. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. [https:// | ||
==Temozolomide & RT, then Temozolomide {{#subobject:06b849|Regimen=1}}== | ==Temozolomide & RT, then Temozolomide {{#subobject:06b849|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:0994f6|Variant=1}}=== | ===Regimen variant #1 {{#subobject:0994f6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 748: | Line 746: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463834/ Chang et al. 2017 (RTOG 9813)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463834/ Chang et al. 2017 (RTOG 9813)] | ||
− | |2002-2007 | + | |2002-2007 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | | | + | |1a. [[#Carmustine_.26_RT_888|Carmustine & RT]]<br>1b. [[#Lomustine_.26_RT_888|Lomustine & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 3.9 vs 3.8 yrs<br>(HR 0.94, 95% CI 0.67-1.32) | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 3.9 vs 3.8 yrs<br>(HR 0.94, 95% CI 0.67-1.32) | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Temozolomide (Temodar)]] as follows: | |
− | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | + | **Cycle 1 (chemoradiation): 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, 29 to 33 |
− | + | **Cycles 2 to 11: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 1 | + | **Cycle 1 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45 (33 fractions; total dose of 5940 cGy) |
− | + | '''8-week course, then 28-day cycle for 10 cycles''' | |
− | ''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | === | + | ===Regimen variant #2 {{#subobject:9b51b7|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 780: | Line 778: | ||
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ van den Bent et al. 2017 (CATNON)] | | rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ van den Bent et al. 2017 (CATNON)] | ||
|rowspan=2|2007-2015 | |rowspan=2|2007-2015 | ||
− | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
− | |1. [[#Radiation_therapy|RT]]<br> 2. [[#Temozolomide_.26_RT|Temozolomide & RT]] | + | |1. [[#Radiation_therapy|RT]]<br>2. [[#Temozolomide_.26_RT|Temozolomide & RT]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint) |
|- | |- | ||
|3. [[#RT.2C_then_Temozolomide|RT, then Temozolomide]] | |3. [[#RT.2C_then_Temozolomide|RT, then Temozolomide]] | ||
Line 788: | Line 786: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
''This study excluded patients with [[Biomarkers#Chromosomal regions#1p19q|1p19q codeletions]]. As of WHO 2016 [[Biomarkers#genes|IDH mutated]], [[Biomarkers#Chromosomal regions#1p19q|1p19q co-deleted]] tumors are classified as oligodendroglioma . This study is of Anaplastic Astrocytoma and included patients with both [[Biomarkers#genes|IDH mutant]] and IDH wild-type astrocytomas.'' | ''This study excluded patients with [[Biomarkers#Chromosomal regions#1p19q|1p19q codeletions]]. As of WHO 2016 [[Biomarkers#genes|IDH mutated]], [[Biomarkers#Chromosomal regions#1p19q|1p19q co-deleted]] tumors are classified as oligodendroglioma . This study is of Anaplastic Astrocytoma and included patients with both [[Biomarkers#genes|IDH mutant]] and IDH wild-type astrocytomas.'' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#CNS_cancer_surgery|Surgery]] | *[[Surgery#CNS_cancer_surgery|Surgery]] | ||
− | + | </div> | |
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | *[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day | + | *[[Temozolomide (Temodar)]] as follows: |
− | + | **Cycle 1 (chemoradiation): 75 mg/m<sup>2</sup> PO once per day on days 1 to 45, given during radiation therapy, including non-treatment weekend days | |
− | + | **Cycle 2: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach | |
+ | **Cycles 3 to 13: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5, taken on an empty stomach | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45 (33 fractions; total dose of 5940 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 1 | + | '''11-week course, then 28-day cycle for 12 cycles''' |
− | + | </div></div> | |
− | ''' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | #'''RTOG 9813:''' Chang S, Zhang P, Cairncross JG, Gilbert MR, Bahary JP, Dolinskas CA, Chakravarti A, Aldape KD, Bell EH, Schiff D, Jaeckle K, Brown PD, Barger GR, Werner-Wasik M, Shih H, Brachman D, Penas-Prado M, Robins HI, Belanger K, Schultz C, Hunter G, Mehta M. Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813. Neuro Oncol. 2017 Feb 1;19(2):252-258. [https://doi.org/10.1093/neuonc/now236 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463834/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27994066/ PubMed] [https://clinicaltrials.gov/study/NCT00004259 NCT00004259] | |
− | #'''RTOG 9813:''' Chang S, Zhang P, Cairncross JG, Gilbert MR, Bahary JP, Dolinskas CA, Chakravarti A, Aldape KD, Bell EH, Schiff D, Jaeckle K, Brown PD, Barger GR, Werner-Wasik M, Shih H, Brachman D, Penas-Prado M, Robins HI, Belanger K, Schultz C, Hunter G, Mehta M. Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813. Neuro Oncol. 2017 Feb 1;19(2):252-258. [https:// | + | #'''CATNON:''' van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; [[Study_Groups#EORTC|EORTC]]. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. [https://doi.org/10.1016/S0140-6736(17)31442-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806535/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28801186/ PubMed] [https://clinicaltrials.gov/study/NCT00626990 NCT00626990] |
− | #'''CATNON:''' van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; [[Study_Groups#EORTC|EORTC]]. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. [https:// | ||
=Recurrent disease, salvage therapy= | =Recurrent disease, salvage therapy= | ||
==Bevacizumab monotherapy {{#subobject:e5af45|Regimen=1}}== | ==Bevacizumab monotherapy {{#subobject:e5af45|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:a83fc7|Variant=1}}=== | ===Regimen {{#subobject:a83fc7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1007/s11060-008-9722-2 Chamberlain et al. 2008a] | |[https://doi.org/10.1007/s11060-008-9722-2 Chamberlain et al. 2008a] | ||
+ | |2005-01 to 2008-03 | ||
| style="background-color:#ffffbe" |Retrospective | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV over 30 minutes once on day 1 | *[[Bevacizumab (Avastin)]] 10 mg/kg IV over 30 minutes once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*Use of [[:Category:Steroids|steroids]] allowed for control of neurologic signs and symptoms | *Use of [[:Category:Steroids|steroids]] allowed for control of neurologic signs and symptoms | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''Retrospective:''' Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol. 2009 Feb;91(3):359-67. Epub 2008 Oct 25. J Neurooncol. 2009 Feb;91(3):359-67. Epub 2008 Oct 25. [https://doi.org/10.1007/s11060-008-9722-2 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18953491/ PubMed] | |
− | #'''Retrospective:''' Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol. 2009 Feb;91(3):359-67. Epub 2008 Oct 25. J Neurooncol. 2009 Feb;91(3):359-67. Epub 2008 Oct 25. [https://doi.org/10.1007/s11060-008-9722-2 link to original article] ''' | + | #'''Retrospective:''' Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009 Apr 15;115(8):1734-43. [https://doi.org/10.1002/cncr.24179 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19197992/ PubMed] |
− | #'''Retrospective:''' Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009 Apr 15;115(8):1734-43. [https:// | ||
− | |||
==Carboplatin & Bevacizumab {{#subobject:35870a|Regimen=1}}== | ==Carboplatin & Bevacizumab {{#subobject:35870a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, q2wk bevacizumab {{#subobject:fe380b|Variant=1}}=== | ===Regimen variant #1, q2wk bevacizumab {{#subobject:fe380b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1212/01.wnl.0000304121.57857.38 Norden et al. 2008] |
+ | |2005-06 to 2007-03 | ||
| style="background-color:#ffffbe" |Retrospective | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV (reference does not list schedule of carboplatin) once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV (reference does not list schedule of carboplatin) once on day 1 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, q4wk bevacizumab {{#subobject:419b2e|Variant=1}}=== | ===Regimen variant #2, q4wk bevacizumab {{#subobject:419b2e|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1227%2F01.NEU.0000370918.51053.BC Thompson et al. 2010] |
+ | |2006-2008 | ||
| style="background-color:#ffffbe" |Retrospective | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1 | ||
− | + | '''28-day cycles''' | |
− | '''28-day cycles''' | + | |
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1212/01.wnl.0000304121.57857.38 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18316689/ PubMed] | |
− | #'''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. [ | + | #'''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. [https://doi.org/10.1227%2F01.NEU.0000370918.51053.BC link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905718/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20559095/ 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. [ | ||
==Cyclophosphamide monotherapy {{#subobject:270740|Regimen=1}}== | ==Cyclophosphamide monotherapy {{#subobject:270740|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:cd7eda|Variant=1}}=== | ===Regimen {{#subobject:cd7eda|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.21582 Chamberlain et al. 2006] |
+ | |1999-2004 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Temozolomide exposure | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2 | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms | *[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms | ||
− | *[[Ondansetron (Zofran)]] 0.15 mg/kg IV once per day on days 1 & 2, prior to | + | *[[Ondansetron (Zofran)]] 0.15 mg/kg IV once per day on days 1 & 2, prior to cyclophosphamide |
− | *[[Dexamethasone (Decadron)]] 4 mg IV once per day on days 1 & 2, prior to | + | *[[Dexamethasone (Decadron)]] 4 mg IV once per day on days 1 & 2, prior to cyclophosphamide |
− | *1 liter normal saline IV over 2 hours once per day on days 1 & 2, prior to | + | *1 liter normal saline IV over 2 hours once per day on days 1 & 2, prior to cyclophosphamide |
*[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting | *[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Chamberlain MC, Tsao-Wei DD, Groshen S. Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma. Cancer. 2006 Jan 1;106(1):172-9. [https://doi.org/10.1002/cncr.21582 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16323194/ PubMed] | |
− | #Chamberlain MC, Tsao-Wei DD, Groshen S. Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma. Cancer. 2006 Jan 1;106(1):172-9. [https:// | ||
==Etoposide monotherapy {{#subobject:f2f865|Regimen=1}}== | ==Etoposide monotherapy {{#subobject:f2f865|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:9960a7|Variant=1}}=== | ===Regimen {{#subobject:9960a7|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1007/bf00177478 Fulton et al. 1996] |
+ | |1991-1994 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Etoposide (Vepesid)]] 50 mg PO once per day | *[[Etoposide (Vepesid)]] 50 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Fulton D, Urtasun R, Forsyth P. Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol. 1996 Feb;27(2):149-55. [https://doi.org/10.1007/bf00177478 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8699237/ PubMed] | |
− | #Fulton D, Urtasun R, Forsyth P. Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol. 1996 Feb;27(2):149-55. [ | ||
==Irinotecan monotherapy {{#subobject:44d48a|Regimen=1}}== | ==Irinotecan monotherapy {{#subobject:44d48a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, 125 mg/m<sup>2</sup>, 4 out of 6 weeks {{#subobject:2512a2|Variant=1}}=== | ===Regimen variant #1, 125 mg/m<sup>2</sup>, 4 out of 6 weeks {{#subobject:2512a2|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1999.17.5.1516 Friedman et al. 1999] | |[https://doi.org/10.1200/jco.1999.17.5.1516 Friedman et al. 1999] | ||
+ | |1996-1997 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
− | + | ====Supportive therapy==== | |
− | |||
− | ====Supportive | ||
− | |||
*[[:Category:Steroids|Steroids]] at lowest dose necessary | *[[:Category:Steroids|Steroids]] at lowest dose necessary | ||
*Avoid laxatives and magnesium-containing antacids due to potential for diarrhea | *Avoid laxatives and magnesium-containing antacids due to potential for diarrhea | ||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *If tolerated, irinotecan dose could be increased to 150 mg/m<sup>2</sup> | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 350 mg/m<sup>2</sup> q3wk {{#subobject:31e6bc|Variant=1}}=== | ===Regimen variant #2, 350 mg/m<sup>2</sup> q3wk {{#subobject:31e6bc|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.23404 Chamberlain et al. 2008b] |
+ | |2000-2007 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV over 2 hours once on day 1 | *[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV over 2 hours once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*As described by Chamberlain et al. 2008b: | *As described by Chamberlain et al. 2008b: | ||
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms | *[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms | ||
− | *500 mL normal saline IV over 60 minutes once on day 1, prior to | + | *500 mL normal saline IV over 60 minutes once on day 1, prior to irinotecan |
*One of the following serotonin 5-HT3 antagonists: | *One of the following serotonin 5-HT3 antagonists: | ||
− | **[[Ondansetron (Zofran)]] IV (dose not specified) once on day 1, prior to | + | **[[Ondansetron (Zofran)]] IV (dose not specified) once on day 1, prior to irinotecan |
− | **[[Granisetron]] IV (dose not specified) once on day 1, prior to | + | **[[Granisetron]] IV (dose not specified) once on day 1, prior to irinotecan |
− | **[[Dolasetron (Anzemet)]] IV (dose not specified) once on day 1, prior to | + | **[[Dolasetron (Anzemet)]] IV (dose not specified) once on day 1, prior to irinotecan |
− | *[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, prior to | + | *[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, prior to irinotecan |
− | *[[Atropine (Atropen)]] 0.5 mg IV once on day 1, prior to | + | *[[Atropine (Atropen)]] 0.5 mg IV once on day 1, prior to irinotecan |
*[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting | *[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting | ||
*[[Loperamide (Imodium)]] (dose/schedule not specified) prn diarrhea | *[[Loperamide (Imodium)]] (dose/schedule not specified) prn diarrhea | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 600 mg/m<sup>2</sup> q3wk {{#subobject:370eb3|Variant=1}}=== | ===Regimen variant #3, 600 mg/m<sup>2</sup> q3wk {{#subobject:370eb3|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1023/a:1019608404378 Chamberlain 2002] |
+ | |Not reported | ||
| style="background-color:#ffffbe" |Phase 1 | | style="background-color:#ffffbe" |Phase 1 | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.23404 Chamberlain et al. 2008b] |
+ | |2000-2007 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: this is the dose recommended for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs).'' | ''Note: this is the dose recommended for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs).'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Chamberlain et al. 2008b: Temozolomide exposure | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 600 mg/m<sup>2</sup> IV over 2 hours once on day 1 | *[[Irinotecan (Camptosar)]] 600 mg/m<sup>2</sup> IV over 2 hours once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*As described by Chamberlain et al. 2008b: | *As described by Chamberlain et al. 2008b: | ||
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms | *[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms | ||
− | *500 mL normal saline IV over 60 minutes, prior to | + | *500 mL normal saline IV over 60 minutes, prior to irinotecan |
*One of the following serotonin 5-HT3 antagonists: | *One of the following serotonin 5-HT3 antagonists: | ||
− | **[[Ondansetron (Zofran)]] IV (dose not specified) once on day 1, prior to | + | **[[Ondansetron (Zofran)]] IV (dose not specified) once on day 1, prior to irinotecan |
− | **[[Granisetron]] IV (dose not specified) once on day 1, prior to | + | **[[Granisetron]] IV (dose not specified) once on day 1, prior to irinotecan |
− | **[[Dolasetron (Anzemet)]] IV (dose not specified) once on day 1, prior to | + | **[[Dolasetron (Anzemet)]] IV (dose not specified) once on day 1, prior to irinotecan |
− | *[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, prior to | + | *[[Dexamethasone (Decadron)]] 20 mg IV once on day 1, prior to irinotecan |
− | *[[Atropine (Atropen)]] 0.5 mg IV once on day 1, prior to | + | *[[Atropine (Atropen)]] 0.5 mg IV once on day 1, prior to irinotecan |
*[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting | *[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting | ||
*[[Loperamide (Imodium)]] (dose/schedule not specified) prn diarrhea | *[[Loperamide (Imodium)]] (dose/schedule not specified) prn diarrhea | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===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. [https://doi.org/10.1200/jco.1999.17.5.1516 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10334539/ PubMed] | |
− | #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. [https://doi.org/10.1200/jco.1999.17.5.1516 link to original article] ''' | + | #'''Phase 1:''' Chamberlain MC. Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol. 2002 Sep;59(2):157-63. [https://doi.org/10.1023/a:1019608404378 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12241109/ PubMed] |
− | #'''Phase | + | #Chamberlain MC, Wei-Tsao DD, Blumenthal DT, Glantz MJ. Salvage chemotherapy with CPT-11 for recurrent temozolomide-refractory anaplastic astrocytoma. Cancer. 2008 May 1;112(9):2038-45. [https://doi.org/10.1002/cncr.23404 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18361434/ PubMed] |
− | #Chamberlain MC, Wei-Tsao DD, Blumenthal DT, Glantz MJ. Salvage chemotherapy with CPT-11 for recurrent temozolomide-refractory anaplastic astrocytoma. Cancer. 2008 May 1;112(9):2038-45. [https:// | ||
− | |||
==Irinotecan & Bevacizumab {{#subobject:6cc49b|Regimen=1}}== | ==Irinotecan & Bevacizumab {{#subobject:6cc49b|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:b04dbd|Variant=1}}=== | ===Regimen {{#subobject:b04dbd|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1158/1078-0432.CCR-06-2309 Vredenburgh et al. 2007] |
+ | |Not reported | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
''Note: Vredenburgh et al. 2007 described 6-week cycles in which treatment was every 2 weeks and was otherwise identical, so its entry was consolidated with Taillibert et al. 2009.'' | ''Note: Vredenburgh et al. 2007 described 6-week cycles in which treatment was every 2 weeks and was otherwise identical, so its entry was consolidated with Taillibert et al. 2009.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first''' | *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first''' | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1, '''given second''' | *[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1, '''given second''' | ||
**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 | **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 therapy==== | |
− | ====Supportive | ||
− | |||
*"Appropriate antiemetics" | *"Appropriate antiemetics" | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose of irinotecan: 340 mg/m<sup>2</sup> | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #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. [https://doi.org/10.1158/1078-0432.CCR-06-2309 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17317837/ 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. [ | + | ##'''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. [https://doi.org/10.1200/jco.2007.12.2440 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17947719/ 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. [https://doi.org/10.1200/jco.2007.12.2440 link to original article] ''' | + | #'''Retrospective:''' Taillibert S, Vincent LA, Granger B, Marie Y, Carpentier C, Guillevin R, Bellanger A, Mokhtari K, Rousseau A, Psimaras D, Dehais C, Sierra del Rio M, Meng Y, Laigle-Donadey F, Hoang-Xuan K, Sanson M, Delattre JY. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009 May 5;72(18):1601-6. [https://doi.org/10.1212/wnl.0b013e3181a413be link to original article] [https://pubmed.ncbi.nlm.nih.gov/19414728/ PubMed] |
− | #'''Retrospective:''' Taillibert S, Vincent LA, Granger B, Marie Y, Carpentier C, Guillevin R, Bellanger A, Mokhtari K, Rousseau A, Psimaras D, Dehais C, Sierra del Rio M, Meng Y, Laigle-Donadey F, Hoang-Xuan K, Sanson M, Delattre JY. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009 May 5;72(18):1601-6. [ | ||
==PCV {{#subobject:1d08ed|Regimen=1}}== | ==PCV {{#subobject:1d08ed|Regimen=1}}== | ||
− | |||
PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''incristine | PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''incristine | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1 {{#subobject:ee0c51|Variant=1}}=== | ===Regimen variant #1 {{#subobject:ee0c51|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,079: | Line 1,080: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[#Radiation_therapy|RT]] or salvage [[#Temozolomide_monotherapy_2|temozolomide]] or salvage [[#Radiation_therapy_2|RT]], with progression | |
− | *[[#Radiation_therapy|RT]] or [[#Temozolomide_monotherapy_2| | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 2 mg IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 2 mg IV once per day on days 8 & 29 | ||
− | |||
'''8-week cycles''' | '''8-week cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *NOA-04, upon progression, patients who had not previously received temozolomide: Salvage [[#Temozolomide_monotherapy_2|temozolomide]] | |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #2 {{#subobject:d8f8c2|Variant=1}}=== | ===Regimen variant #2 {{#subobject:d8f8c2|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://pubmed.ncbi.nlm.nih.gov/7407756 Levin et al. 1980] | |[https://pubmed.ncbi.nlm.nih.gov/7407756 Levin et al. 1980] | ||
+ | |Not reported in abstract | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 110 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8 & 29 | ||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, higher doses {{#subobject:eacf9b|Variant=1}}=== | ===Regimen variant #3, higher doses {{#subobject:eacf9b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.1994.12.10.2013 Cairncross et al. 1994] | |[https://doi.org/10.1200/jco.1994.12.10.2013 Cairncross et al. 1994] | ||
+ | |1989-1992 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Procarbazine (Matulane)]] 75 mg/m<sup>2</sup> PO once per day on days 8 to 21 | *[[Procarbazine (Matulane)]] 75 mg/m<sup>2</sup> PO once per day on days 8 to 21 | ||
*[[Lomustine (CCNU)]] 130 mg/m<sup>2</sup> PO once on day 1 | *[[Lomustine (CCNU)]] 130 mg/m<sup>2</sup> PO once on day 1 | ||
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 8 & 29 | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 8 & 29 | ||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7407756/ PubMed] | |
− | #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. ''' | + | #Cairncross G, Macdonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr, Wainman N, Eisenhauer E; National Cancer Institute of Canada Clinical Trials Group. Chemotherapy for anaplastic oligodendroglioma. J Clin Oncol. 1994 Oct;12(10):2013-21. [https://doi.org/10.1200/jco.1994.12.10.2013 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7931469/ PubMed] |
− | #Cairncross G, Macdonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr, Wainman N, Eisenhauer E; National Cancer Institute of Canada Clinical Trials Group. Chemotherapy for anaplastic oligodendroglioma. J Clin Oncol. 1994 Oct;12(10):2013-21. [https://doi.org/10.1200/jco.1994.12.10.2013 link to original article] ''' | + | #'''Retrospective:''' Kappelle AC, Postma TJ, Taphoorn MJ, Groeneveld GJ, van den Bent MJ, van Groeningen CJ, Zonnenberg BA, Sneeuw KC, Heimans JJ. PCV chemotherapy for recurrent glioblastoma multiforme. Neurology. 2001 Jan 9;56(1):118-20. [https://doi.org/10.1212/wnl.56.1.118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11148250/ PubMed] |
− | #'''Retrospective:''' Kappelle AC, Postma TJ, Taphoorn MJ, Groeneveld GJ, van den Bent MJ, van Groeningen CJ, Zonnenberg BA, Sneeuw KC, Heimans JJ. PCV chemotherapy for recurrent glioblastoma multiforme. Neurology. 2001 Jan 9;56(1):118-20. [ | + | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19901110/ PubMed] [https://clinicaltrials.gov/study/NCT00717210 NCT00717210] |
− | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] ''' | + | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https://doi.org/10.1093/neuonc/now133 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27370396/ PubMed] |
− | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https:// | ||
==Radiation therapy {{#subobject:1bc97f|Regimen=1}}== | ==Radiation therapy {{#subobject:1bc97f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:474304|Variant=1}}=== | ===Regimen {{#subobject:474304|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,157: | Line 1,160: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *Adjuvant [[#PCV|PCV]] versus [[#Temozolomide_monotherapy|temozolomide]], with progression | |
− | *[[#PCV|PCV]] versus [[#Temozolomide_monotherapy|temozolomide]], with progression | + | </div> |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *[[External beam radiotherapy]] with 1.8 to 200 cGy fractions for a total dose of 6000 cGy | |
− | *[[External beam radiotherapy]] with 1.8 to | ||
− | |||
'''6-week course''' | '''6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *NOA-04, at progression: Salvage [[#PCV_2|PCV]] if they had previously received temozolomide or [[#Temozolomide_monotherapy_2|temozolomide]] if they had previously received PCV | |
− | * | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19901110/ PubMed] [https://clinicaltrials.gov/study/NCT00717210 NCT00717210] | |
− | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] ''' | + | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https://doi.org/10.1093/neuonc/now133 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27370396/ PubMed] |
− | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https:// | ||
− | |||
==Temozolomide monotherapy {{#subobject:75970a|Regimen=1}}== | ==Temozolomide monotherapy {{#subobject:75970a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen variant #1 {{#subobject:f83563|Variant=1}}=== | ===Regimen variant #1 {{#subobject:f83563|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,193: | Line 1,194: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[#Radiation_therapy|RT]] or salvage [[#PCV_2|PCV]] or salvage [[#Radiation_therapy_2|RT]], with progression | |
− | *[[#Radiation_therapy|RT]] or [[#PCV_2| | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *NOA-04, upon progression, patients who had not previously received PCV: Salvage [[#PCV_2|PCV]] | |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #2, continuous therapy {{#subobject:276de1|Variant=1}}=== | ===Regimen variant #2, continuous therapy {{#subobject:276de1|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.23813 Perry et al. 2008 (RESCUE)] |
− | | style="background-color:# | + | |2001-01 to 2005-07 |
+ | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
− | ''Patients who undergo conventional temozolomide therapy, have surgery and radiation therapy, and then relapse receive:'' | + | ''Note: Patients who undergo conventional temozolomide therapy, have surgery and radiation therapy, and then relapse receive:'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Temozolomide (Temodar)]] 150 to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | *[[Temozolomide (Temodar)]] 150 to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | |||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Subsequent treatment==== | ||
+ | *RESCUE, upon progression: Salvage [[#Temozolomide_monotherapy|temozolomide]]; 50 mg/m<sup>2</sup> PO once per day | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3 {{#subobject:52f20c|Variant=1}}=== | ===Regimen variant #3 {{#subobject:52f20c|Variant=1}}=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/jco.1999.17.9.2762 Yung et al. 1999] | + | |[https://doi.org/10.1200/jco.1999.17.9.2762 Yung et al. 1999 (MK-7365-006)] |
− | | | + | |Not reported |
| style="background-color:#91cf61" |Phase 2 (RT) | | style="background-color:#91cf61" |Phase 2 (RT) | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Temozolomide (Temodar)]] by the following exposure-based criteria: | |
− | *[[Temozolomide (Temodar)]] by the following criteria: | ||
**Patients who had never previously received chemotherapy: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | **Patients who had never previously received chemotherapy: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | **Patients who previously received chemotherapy: 150 | + | **Patients who previously received chemotherapy: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*Prophylactic [[:Category:Emesis_prevention|antiemetics]] as needed | *Prophylactic [[:Category:Emesis_prevention|antiemetics]] as needed | ||
*Lowest dose of [[:Category:Steroids|corticosteroids]] necessary to maintain neurologic stability | *Lowest dose of [[:Category:Steroids|corticosteroids]] necessary to maintain neurologic stability | ||
− | |||
'''28-day cycle for up to 26 cycles (2 years)''' | '''28-day cycle for up to 26 cycles (2 years)''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *If tolerated in patients who previously received chemotherapy, temozolomide dose could be increased to 200 mg/m<sup>2</sup> | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''MK-7365-006:''' Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O'Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA; Temodal Brain Tumor Group. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol. 1999 Sep;17(9):2762-71. [https://doi.org/10.1200/jco.1999.17.9.2762 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10561351/ PubMed] | |
− | #Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O'Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA; Temodal Brain Tumor Group. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol. 1999 Sep;17(9):2762-71. [https://doi.org/10.1200/jco.1999.17.9.2762 link to original article] ''' | + | #'''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. [https://doi.org/10.1002/cncr.23813 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18756530/ PubMed] [https://clinicaltrials.gov/study/NCT00392171 NCT00392171] |
− | #'''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. [https:// | + | ##'''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. [https://doi.org/10.1200/jco.2009.26.5520 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20308655/ 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. [https://doi.org/10.1200/jco.2009.26.5520 link to original article] ''' | + | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19901110/ PubMed] [https://clinicaltrials.gov/study/NCT00717210 NCT00717210] |
− | #'''NOA-04:''' Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. [https://doi.org/10.1200/jco.2009.23.6497 link to original article] ''' | + | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https://doi.org/10.1093/neuonc/now133 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063521/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27370396/ PubMed] |
− | ##'''Update:''' Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. [https:// | ||
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[[Category:Anaplastic glioma regimens]] | [[Category:Anaplastic glioma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:High-grade gliomas]] | [[Category:High-grade gliomas]] |
Latest revision as of 01:12, 21 July 2024
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.
If you are looking for other subtypes of brain cancer, please go to the CNS cancers category page.
18 regimens on this page
36 variants on this page
|
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.
ASCO/SNO
- 2022: Mohile et al. Therapy for Diffuse Astrocytic and Oligodendroglial Tumors in Adults: ASCO-SNO Guideline PubMed
EANO
- 2017: European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma (2017) PubMed
- 2014: EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma (2014) PubMed
ESMO
- High-grade glioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2014) PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Central Nervous System Cancers and related JNCCN publications below.
Adjuvant therapy
Carmustine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chang et al. 1983 | 1974-1979 | Phase 3 (E-esc) | RT alone | Did not meet primary endpoint of OS |
Levin et al. 1985 (NCOG 6G61) | 1977-1983 | Phase 3 (C) | PCV | Seems to have inferior OS1 |
Halperin et al. 1996 | 1988-11 to 1991-12 | Phase 3 (C) | Carmustine & Mercaptopurine | Did not meet endpoint of OS |
1Reported efficacy for NCOG 6G61 is based on the 1990 update.
Note: Chang et al. 1983 was technically a negative study, although the subgroup of patients aged 40 to 60 had superior survival in this arm.
Preceding treatment
- Chang et al. 1983: Surgery, then adjuvant RT
- NCOG 6G61: Surgery, then adjuvant Hydrea & WBRT
References
- Chang CH, Horton J, Schoenfeld D, Salazer O, Perez-Tamayo R, Kramer S, Weinstein A, Nelson JS, Tsukada Y; RTOG; ECOG. Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas: a joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study. Cancer. 1983 Sep 15;52(6):997-1007. link to original article PubMed
- NCOG 6G61: Levin VA, Wara WM, Davis RL, Vestnys P, Resser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB. Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas. J Neurosurg. 1985 Aug;63(2):218-23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4. link to original article PubMed
- Halperin EC, Herndon J, Schold SC, Brown M, Vick N, Cairncross JG, Macdonald DR, Gaspar L, Fischer B, Dropcho E, Rosenfeld S, Morowitz R, Piepmeier J, Hait W, Byrne T, Salter M, Imperato J, Khandekar J, Paleologos N, Burger P, Bentel GC, Friedman A; CNS Cancer Consortium. A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. Int J Radiat Oncol Biol Phys. 1996 Mar 1;34(4):793-802. link to original article dosing details in abstract have been reviewed by our editors PubMed
PCV
PCV: Procarbazine, CCNU, Vincristine
Regimen variant #1, 60/110/1.4 (capped)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Levin et al. 2003 | 1992-1999 | Phase 3 (C) | PCV & DMFO | Did not meet primary endpoint of OS1 |
van den Bent et al. 2006 (EORTC 26951) | 1996-2002 | Phase 3 (E-esc) | No further treatment | Seems to have superior OS2 (primary endpoint) Median OS: 3.5 vs 2.6 y (HR 0.78, 95% CI 0.63-0.98) |
1Levin et al. 2003 had a complex hazard function; see paper for details.
2Reported efficacy for EORTC 26951 is based on the 2022 update.
Chemotherapy begins within 4 weeks after completion of radiation therapy:
Biomarker eligibility criteria
- 1p/19q co-deletion: As of WHO 2016 IDH mutated, 1p/19q co-deleted tumors are classified as oligodendroglioma
- EORTC 26951: van den Bent et al. 2013 noted that 1p/19q co-deleted tumors received the more benefit from adjuvant PCV as compared to tumors without 1p/19q co-deletion.
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
- Antiemetics for lomustine: "Domperidone (Motilium) or Metoclopramide (Reglan), and if necessary, Ondansetron (Zofran) or a similar agent"
- Corticosteroids kept at lowest possible dose
42-day cycle for 6 cycles (EORTC 26951) or 7 cycles (Levin et al. 2003)
Regimen variant #2, 60/110/1.4 (no cap)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Levin et al. 1985 (NCOG 6G61) | 1977-1983 | Phase 3 (E-esc) | BCNU | Seems to have superior OS1 |
1Reported efficacy is based on the 1990 update.
Note: the total number of cycles is not specified in this protocol.
Preceding treatment
- Surgery, then adjuvant Hydrea & WBRT
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 IV once per day on days 8 & 29
6- to 8-week cycles
Regimen variant #3, 60/110/2 x 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wick et al. 2009 (NOA-04) | 1999-2005 | Phase 3 (E-esc) | 1. RT | Did not meet primary endpoint of TTF |
2. Temozolomide | Did not meet primary endpoint of TTF |
Preceding treatment
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) 2 mg IV once per day on days 8 & 29
8-week cycle for 4 cycles
Regimen variant #4, 75/130/1.4 (no cap) x 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Prados et al. 1999 (RTOG 9404) | 1991-1997 | Phase 3 (C) | PCV & BUdR | Did not meet co-primary endpoints of TTP/OS |
Cairncross et al. 2006 (RTOG 9402) | 1994-2002 | Phase 3 (E-esc) | No chemotherapy | Might have superior OS1 (primary endpoint) Median OS: 4.8 vs 4.8 y (HR 0.79, 95% CI 0.61-1.03) |
1Reported efficacy for RTOG 9402 is based on the 2022 update.
Note: the abstract of Prados et al. 2004 does not have dosing details.
Biomarker eligibility criteria
- 1p/19q co-deletion: As of WHO 2016 IDH mutated, 1p/19q co-deleted tumors are classified as oligodendroglioma
- RTOG 9402: a survival benefit was noted in the population with 1p/19q co-deleted tumors
Preceding treatment
Chemotherapy
- Procarbazine (Matulane) 75 mg/m2 PO once per day on days 8 to 21
- Lomustine (CCNU) 130 mg/m2 PO once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once per day on days 8 & 29
6-week cycle for 4 cycles
Subsequent treatment
- Adjuvant RT x 5040 cGy + 900 cGy boost
Regimen variant #5, 100/100/1.5 (capped) x 12
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thomas et al. 2001 (MRC BR05) | 1988-1997 | Phase 3 (E-esc) | No further treatment | Did not meet primary endpoint of OS24 |
Chemotherapy begins 3 to 4 weeks after completion of radiation therapy.
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
Supportive therapy
- Corticosteroid use was left up to physician discretion. It was recommended to not discontinue steroids until at least 6 weeks after radiation therapy. If it was to be discontinued, it should be tapered down gradually over several weeks, or could be titrated down to the lowest tolerated dose.
42-day cycle for up to 12 cycles
References
- NCOG 6G61: Levin VA, Wara WM, Davis RL, Vestnys P, Resser KJ, Yatsko K, Nutik S, Gutin PH, Wilson CB. Phase III comparison of BCNU and the combination of procarbazine, CCNU, and vincristine administered after radiotherapy with hydroxyurea for malignant gliomas. J Neurosurg. 1985 Aug;63(2):218-23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Levin VA, Silver P, Hannigan J, Wara WM, Gutin PH, Davis RL, Wilson CB. Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. Int J Radiat Oncol Biol Phys. 1990 Feb;18(2):321-4. link to original article PubMed
- MRC BR05: Thomas D, Brada M, Stenning S; Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001 Jan 15;19(2):509-18. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Levin VA, Hess KR, Choucair A, Flynn PJ, Jaeckle KA, Kyritsis AP, Yung WK, Prados MD, Bruner JM, Ictech S, Gleason MJ, Kim HW. Phase III randomized study of postradiotherapy chemotherapy with combination alpha-difluoromethylornithine-PCV versus PCV for anaplastic gliomas. Clin Cancer Res. 2003 Mar;9(3):981-90. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- RTOG 9404: Prados MD, Scott C, Sandler H, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404. Int J Radiat Oncol Biol Phys. 1999 Dec 1;45(5):1109-15. link to original article PubMed
- Update: Prados MD, Seiferheld W, Sandler HM, Buckner JC, Phillips T, Schultz C, Urtasun R, Davis R, Gutin P, Cascino TL, Greenberg HS, Curran WJ Jr. Phase III randomized study of radiotherapy plus procarbazine, lomustine, and vincristine with or without BUdR for treatment of anaplastic astrocytoma: final report of RTOG 9404. Int J Radiat Oncol Biol Phys. 2004 Mar 15;58(4):1147-52. link to original article PubMed
- RTOG 9402: Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002569
- Update: Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. Epub 2012 Oct 15. link to original article link to PMC article PubMed
- Pooled update: Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. link to original article link to PMC article PubMed
- EORTC 26951: van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006 Jun 20;24(18):2715-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002840
- Update: van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013 Jan 20;31(3):344-50. Epub 2012 Oct 15. link to original article PubMed
- Pooled update: Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. link to original article link to PMC article PubMed
- NOA-04: Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00717210
- Update: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. link to original article link to PMC article PubMed
Radiation therapy
Regimen variant #1, 4500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bleehen et al. 1991 (MRC BR02) | 1983-1988 | Phase 3 (C) | RT x 6000 cGy | Inferior OS |
Thomas et al. 2001 (MRC BR05) | 1988-1997 | Non-randomized part of phase 3 RCT |
Radiation therapy starts preferably within 3, but no more than 6, weeks after neurosurgery.
Preceding treatment
Radiotherapy
- External beam radiotherapy 225 cGy fractions x 20 fractions (total dose of 4500 cGy)
4-week course
Subsequent treatment
- MRC BR05: Adjuvant PCV versus no further treatment
Regimen variant #2, 4500 cGy with 1440 cGy boost
Study | Dates of enrollment | Evidence |
---|---|---|
van den Bent et al. 2006 (EORTC 26951) | 1996-2002 | Non-randomized part of phase 3 RCT |
Radiation therapy starts within 6 weeks after surgery.
Preceding treatment
Radiotherapy
- External beam radiotherapy, 180 cGy fractions x 25 fractions, total dose of 4500 cGy to the planning target volume (PTV-1); then a boost of 180 cGy fractions x 8 fractions, total boost dose of 1440 cGy to the PTV-2, for a total cumulative dose of 5940 cGy
6.5-week course
Subsequent treatment
- Adjuvant PCV versus no further treatment
Regimen variant #3, 5040 cGy with 900 cGy boost
Study | Dates of enrollment | Evidence |
---|---|---|
Cairncross et al. 2006 (RTOG 9402) | 1994-2002 | Non-randomized part of phase 3 RCT |
Radiation therapy starts within 6 weeks after surgery or chemotherapy.
Radiotherapy
- External beam radiotherapy, 180 cGy fractions x 28 fractions, total dose of 5040 cGy to the planning target volume (PTV-1); then a boost of 180 cGy fractions x 5 fractions, total boost dose of 900 cGy to the PTV-2, for a total cumulative dose of 5940 cGy
6.5-week course
Regimen variant #4, 6000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bleehen et al. 1991 (MRC BR02) | 1983-1988 | Phase 3 (E-esc) | RT x 4500 cGy | Superior OS |
Thomas et al. 2001 (MRC BR05) | 1988-1997 | Phase 3 (C) | RT, then PCV | Did not meet primary endpoint of OS24 |
Hildebrand et al. 2008 (EORTC 26882) | 1988-2000 | Phase 3 (C) | BCNU, DBD, RT | Did not meet primary endpoint of OS |
van den Bent et al. 2006 (EORTC 26951) | 1996-2002 | Non-randomized part of phase 3 RCT | ||
Wick et al. 2009 (NOA-04) | 1999-2005 | Phase 3 (C) | 1. PCV | Did not meet primary endpoint of TTF |
2. Temozolomide | Did not meet primary endpoint of TTF |
Note: dosing details are not described in the abstract of Hildebrand et al. 2008.
Preceding treatment
Radiotherapy
- External beam radiotherapy with 180 to 200 cGy fractions for a total dose of 6000 cGy
6-week course
Subsequent treatment
- MRC BR05 & EORTC 26951: Adjuvant PCV versus no further treatment
- NOA-04, upon progression: Salvage PCV versus temozolomide
References
- MRC BR02: Bleehen NM, Stenning SP; Medical Research Council Brain Tumour Working Party. A Medical Research Council trial of two radiotherapy doses in the treatment of grades 3 and 4 astrocytoma. Br J Cancer. 1991 Oct;64(4):769-74. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
- MRC BR05: Thomas D, Brada M, Stenning S; Medical Research Council Brain Tumor Working Party. Randomized trial of procarbazine, lomustine, and vincristine in the adjuvant treatment of high-grade astrocytoma: a Medical Research Council trial. J Clin Oncol. 2001 Jan 15;19(2):509-18. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- RTOG 9402: Cairncross G, Berkey B, Shaw E, Jenkins R, Scheithauer B, Brachman D, Buckner J, Fink K, Souhami L, Laperierre N, Mehta M, Curran W. Phase III trial of chemotherapy plus radiotherapy compared with radiotherapy alone for pure and mixed anaplastic oligodendroglioma: Intergroup Radiation Therapy Oncology Group Trial 9402. J Clin Oncol. 2006 Jun 20;24(18):2707-14. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002569
- Update: Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013 Jan 20;31(3):337-43. Epub 2012 Oct 15. link to original article link to PMC article PubMed
- Pooled update: Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. link to original article link to PMC article PubMed
- EORTC 26951: van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006 Jun 20;24(18):2715-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002840
- Update: van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013 Jan 20;31(3):344-50. Epub 2012 Oct 15. link to original article PubMed
- Pooled update: Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. Epub 2022 Jun 22. link to original article link to PMC article PubMed
- EORTC 26882: Hildebrand J, Gorlia T, Kros JM, Afra D, Frenay M, Omuro A, Stupp R, Lacombe D, Allgeier A, van den Bent MJ; EORTC Brain Tumour Group. Adjuvant dibromodulcitol and BCNU chemotherapy in anaplastic astrocytoma: results of a randomised European Organisation for Research and Treatment of Cancer phase III study (EORTC study 26882). Eur J Cancer. 2008 Jun;44(9):1210-6. Epub 2008 Jan 14. link to original article PubMed NCT00002620
- NOA-04: Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00717210
- Update: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. link to original article link to PMC article PubMed
- NOA-08: Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; Neuro-oncology Working Group of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. Epub 2012 May 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01502241
RT, then Carmustine
Regimen variant #1, WBRT
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shapiro et al. 1989 (BTCG 8001) | 1980-1983 | Phase 3 (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 |
Note: Pulmonary function tests (PFTs) were checked before start of therapy, and then when cumulative dose of Carmustine (BCNU) reaches 800 mg/m2 and 1200 mg/m2.
Preceding treatment
- Surgery, within 3 weeks
Radiotherapy
- Whole-brain External beam radiotherapy, 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
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
8-week cycle for up to 18 cycles (a maximum cumulative carmustine dose of 1500 mg/m2)
Regimen variant #2, WBRT with cone-down
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shapiro et al. 1989 (BTCG 8001) | 1980-1983 | Phase 3 (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 |
Note: Pulmonary function tests (PFTs) were checked before start of therapy, and then when cumulative dose of Carmustine (BCNU) reaches 800 mg/m2 and 1200 mg/m2.
Preceding treatment
- Surgery, within 3 weeks
Radiotherapy
- Whole-brain External beam radiotherapy, 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)
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
8-week cycle for up to 18 cycles (a maximum cumulative carmustine dose of 1500 mg/m2)
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed
RT, then Temozolomide
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van den Bent et al. 2017 (CATNON) | 2007-2015 | Phase 3 (E-RT-esc) | 1. RT 2. Temozolomide & RT |
Superior OS (primary endpoint) OS60: 55.9% vs 44.1% (HR 0.65, 99.145% CI 0.45-0.93) |
3. Temozolomide & RT, then Temozolomide | Not reported |
Biomarker eligibility criteria
This study excluded patients with 1p19q codeletions. As of WHO 2016 IDH mutated, 1p19q co-deleted tumors are classified as oligodendroglioma . This study is of Anaplastic Astrocytoma and included patients with both IDH mutant and IDH wild-type astrocytomas.
Preceding treatment
Radiotherapy
- External beam radiotherapy as follows:
- Cycle 1: 180 cGy x 33 fractions (total dose of 5940 cGy)
Chemotherapy
- Temozolomide (Temodar) as follows:
- Cycle 2: 150 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
- Cycles 3 to 13: 200 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
11-week course, then 28-day cycle for 12 cycles
References
- CATNON: van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; EORTC. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00626990
Temozolomide monotherapy
Regimen variant #1, 100 mg/m2, 7 out of 14 days
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wick et al. 2012 (NOA-08) | 2005-05-15 to 2009-11-02 | Phase 3 (E-switch-ooc) | Radiation therapy | Seems to have non-inferior OS (primary endpoint) Median OS: 8.6 vs 9.6 mo (HR 1.09, 95% CI 0.84-1.42) |
Preceding treatment
Regimen variant #2, 200 mg/m2, 5 out of 28 days x 8 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wick et al. 2009 (NOA-04) | 1999-2005 | Phase 3 (E-esc) | 1. PCV | Did not meet primary endpoint of TTF |
2. Radiation therapy | Did not meet primary endpoint of TTF |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
28-day cycle for 8 cycles
Subsequent treatment
- NOA-04, SD or better: Temozolomide continuation x 4 (12 total)
- NOA-04, upon progression: Salvage RT
Regimen variant #3, 200 mg/m2, 5 out of 28 days x 2y
Study | Dates of enrollment | Evidence |
---|---|---|
Taliansky-Aronov et al. 2006 | Not reported | Non-randomized |
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Corticosteroids could be continued at same dose or reduced, but not increased while on study
28-day cycle for up to 26 cycles (2 years)
Regimen variant #4, 5 out of 28 days, with dose-escalation, indefinite
Study | Dates of enrollment | Evidence |
---|---|---|
Mikkelsen et al. 2009 | Not reported | Non-randomized |
Biomarker eligibility criteria
- 1p/19q loss of heterozygosity (LOH)
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) as follows:
- Cycles 1 & 2: 150 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
- Cycle 3 onwards (if no myelosuppression): 200 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
28-day cycles
References
- Taliansky-Aronov A, Bokstein F, Lavon I, Siegal T. Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial. J Neurooncol. 2006 Sep;79(2):153-7. Epub 2006 Jul 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol. 2009 Mar;92(1):57-63. Epub 2008 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
- NOA-04: Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00717210
- Update: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. link to original article link to PMC article PubMed
- NOA-08: Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M; Neuro-oncology Working Group of German Cancer Society. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol. 2012 Jul;13(7):707-15. Epub 2012 May 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01502241
Temozolomide, then Temozolomide & RT, then Temozolomide
Protocol
Study | Dates of enrollment | Evidence |
---|---|---|
Mikkelsen et al. 2009 | Not reported | Non-randomized |
Biomarker eligibility criteria
- This protocol is meant for patients without 1p/19q loss of heterozygosity (LOH).
Preceding treatment
Chemotherapy, pre-radiation portion
- Temozolomide (Temodar) as follows:
- Cycles 1 & 2: 150 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
- Cycles 3 & 4 (if no myelosuppression): 200 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
28-day cycle for 2 to 4 cycles, followed by:
Chemotherapy, concurrent radiation portion
- Temozolomide (Temodar) 75 mg/m2 PO once per day during radiation therapy
Radiotherapy, concurrent radiation portion
- Concurrent radiation therapy: a total dose of 6000 cGy
One course, followed by:
Chemotherapy, maintenance portion
- Temozolomide (Temodar) 150 to 200 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
28-day cycles
References
- Mikkelsen T, Doyle T, Anderson J, Margolis J, Paleologos N, Gutierrez J, Croteau D, Hasselbach L, Avedissian R, Schultz L. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma. J Neurooncol. 2009 Mar;92(1):57-63. Epub 2008 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
Temozolomide & RT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van den Bent et al. 2017 (CATNON) | 2007-2015 | Phase 3 (E-RT-esc) | 1. RT | Not reported |
2. Temozolomide & RT, then Temozolomide 3. RT, then Temozolomide |
Inferior OS (primary endpoint) |
Biomarker eligibility criteria
This study excluded patients with 1p19q codeletions. As of WHO 2016 IDH mutated, 1p19q co-deleted tumors are classified as oligodendroglioma. This study is of Anaplastic Astrocytoma and included patients with both IDH mutant and IDH wild-type astrocytomas.
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) 75 mg/m2 PO once per day on days 1 to 45
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45 (33 fractions; total dose of 5940 cGy)
45-day course
References
- CATNON: van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; EORTC. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00626990
Temozolomide & RT, then Temozolomide
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chang et al. 2017 (RTOG 9813) | 2002-2007 | Phase 3 (E-switch-ic) | 1a. Carmustine & RT 1b. Lomustine & RT |
Did not meet primary endpoint of OS Median OS: 3.9 vs 3.8 yrs (HR 0.94, 95% CI 0.67-1.32) |
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) as follows:
- Cycle 1 (chemoradiation): 200 mg/m2 PO once per day on days 1 to 5, 29 to 33
- Cycles 2 to 11: 200 mg/m2 PO once per day on days 1 to 5
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 1 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45 (33 fractions; total dose of 5940 cGy)
8-week course, then 28-day cycle for 10 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van den Bent et al. 2017 (CATNON) | 2007-2015 | Phase 3 (E-RT-esc) | 1. RT 2. Temozolomide & RT |
Superior OS (primary endpoint) |
3. RT, then Temozolomide | Not reported |
Biomarker eligibility criteria
This study excluded patients with 1p19q codeletions. As of WHO 2016 IDH mutated, 1p19q co-deleted tumors are classified as oligodendroglioma . This study is of Anaplastic Astrocytoma and included patients with both IDH mutant and IDH wild-type astrocytomas.
Preceding treatment
Chemotherapy
- Temozolomide (Temodar) as follows:
- Cycle 1 (chemoradiation): 75 mg/m2 PO once per day on days 1 to 45, given during radiation therapy, including non-treatment weekend days
- Cycle 2: 150 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
- Cycles 3 to 13: 200 mg/m2 PO once per day on days 1 to 5, taken on an empty stomach
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45 (33 fractions; total dose of 5940 cGy)
11-week course, then 28-day cycle for 12 cycles
References
- RTOG 9813: Chang S, Zhang P, Cairncross JG, Gilbert MR, Bahary JP, Dolinskas CA, Chakravarti A, Aldape KD, Bell EH, Schiff D, Jaeckle K, Brown PD, Barger GR, Werner-Wasik M, Shih H, Brachman D, Penas-Prado M, Robins HI, Belanger K, Schultz C, Hunter G, Mehta M. Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813. Neuro Oncol. 2017 Feb 1;19(2):252-258. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00004259
- CATNON: van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, Brandes AA, Clement PM, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Brachman DG, Taal W, Rudà R, Weller M, McBain C, Reijneveld J, Enting RH, Weber DC, Lesimple T, Clenton S, Gijtenbeek A, Pascoe S, Herrlinger U, Hau P, Dhermain F, van Heuvel I, Stupp R, Aldape K, Jenkins RB, Dubbink HJ, Dinjens WNM, Wesseling P, Nuyens S, Golfinopoulos V, Gorlia T, Wick W, Kros JM; EORTC. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study. Lancet. 2017 Oct 7;390(10103):1645-1653. Epub 2017 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00626990
Recurrent disease, salvage therapy
Bevacizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Chamberlain et al. 2008a | 2005-01 to 2008-03 | Retrospective |
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV over 30 minutes once on day 1
Supportive therapy
- Use of steroids allowed for control of neurologic signs and symptoms
14-day cycles
References
- Retrospective: Chamberlain MC, Johnston S. Salvage chemotherapy with bevacizumab for recurrent alkylator-refractory anaplastic astrocytoma. J Neurooncol. 2009 Feb;91(3):359-67. Epub 2008 Oct 25. J Neurooncol. 2009 Feb;91(3):359-67. Epub 2008 Oct 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009 Apr 15;115(8):1734-43. link to original article PubMed
Carboplatin & Bevacizumab
Regimen variant #1, q2wk bevacizumab
Study | Dates of enrollment | Evidence |
---|---|---|
Norden et al. 2008 | 2005-06 to 2007-03 | Retrospective |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 to 6 IV (reference does not list schedule of carboplatin) once on day 1
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1
14-day cycles
Regimen variant #2, q4wk bevacizumab
Study | Dates of enrollment | Evidence |
---|---|---|
Thompson et al. 2010 | 2006-2008 | Retrospective |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
Targeted therapy
- 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 dosing details in abstract have been reviewed by our editors PubMed
Cyclophosphamide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Chamberlain et al. 2006 | 1999-2004 | Phase 2 |
Prior treatment criteria
- Temozolomide exposure
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 30 minutes once per day on days 1 & 2
Supportive therapy
- 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
- Dexamethasone (Decadron) 4 mg IV once per day on days 1 & 2, prior to cyclophosphamide
- 1 liter normal saline IV over 2 hours once per day on days 1 & 2, prior to cyclophosphamide
- Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
28-day cycles
References
- Chamberlain MC, Tsao-Wei DD, Groshen S. Salvage chemotherapy with cyclophosphamide for recurrent temozolomide-refractory anaplastic astrocytoma. Cancer. 2006 Jan 1;106(1):172-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Etoposide monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Fulton et al. 1996 | 1991-1994 | Phase 2 |
References
- Fulton D, Urtasun R, Forsyth P. Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol. 1996 Feb;27(2):149-55. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Irinotecan monotherapy
Regimen variant #1, 125 mg/m2, 4 out of 6 weeks
Study | Dates of enrollment | Evidence |
---|---|---|
Friedman et al. 1999 | 1996-1997 | Phase 2 |
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive therapy
- Steroids at lowest dose necessary
- Avoid laxatives and magnesium-containing antacids due to potential for diarrhea
42-day cycles
Dose and schedule modifications
- If tolerated, irinotecan dose could be increased to 150 mg/m2
Regimen variant #2, 350 mg/m2 q3wk
Study | Dates of enrollment | Evidence |
---|---|---|
Chamberlain et al. 2008b | 2000-2007 | Phase 2 |
Chemotherapy
- Irinotecan (Camptosar) 350 mg/m2 IV over 2 hours once on day 1
Supportive therapy
- As described by Chamberlain et al. 2008b:
- Dexamethasone (Decadron) allowed for control of neurologic symptoms
- 500 mL normal saline IV over 60 minutes once on day 1, prior to irinotecan
- One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) IV (dose not specified) once on day 1, prior to irinotecan
- Granisetron IV (dose not specified) once on day 1, prior to irinotecan
- Dolasetron (Anzemet) IV (dose not specified) once on day 1, prior to irinotecan
- Dexamethasone (Decadron) 20 mg IV once on day 1, prior to irinotecan
- Atropine (Atropen) 0.5 mg IV once on day 1, prior to irinotecan
- Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
- Loperamide (Imodium) (dose/schedule not specified) prn diarrhea
21-day cycles
Regimen variant #3, 600 mg/m2 q3wk
Study | Dates of enrollment | Evidence |
---|---|---|
Chamberlain 2002 | Not reported | Phase 1 |
Chamberlain et al. 2008b | 2000-2007 | Phase 2 |
Note: this is the dose recommended for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs).
Prior treatment criteria
- Chamberlain et al. 2008b: Temozolomide exposure
Chemotherapy
- Irinotecan (Camptosar) 600 mg/m2 IV over 2 hours once on day 1
Supportive therapy
- As described by Chamberlain et al. 2008b:
- Dexamethasone (Decadron) allowed for control of neurologic symptoms
- 500 mL normal saline IV over 60 minutes, prior to irinotecan
- One of the following serotonin 5-HT3 antagonists:
- Ondansetron (Zofran) IV (dose not specified) once on day 1, prior to irinotecan
- Granisetron IV (dose not specified) once on day 1, prior to irinotecan
- Dolasetron (Anzemet) IV (dose not specified) once on day 1, prior to irinotecan
- Dexamethasone (Decadron) 20 mg IV once on day 1, prior to irinotecan
- Atropine (Atropen) 0.5 mg IV once on day 1, prior to irinotecan
- Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
- Loperamide (Imodium) (dose/schedule not specified) prn diarrhea
21-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 dosing details in manuscript have been reviewed by our editors PubMed
- Phase 1: Chamberlain MC. Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol. 2002 Sep;59(2):157-63. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Chamberlain MC, Wei-Tsao DD, Blumenthal DT, Glantz MJ. Salvage chemotherapy with CPT-11 for recurrent temozolomide-refractory anaplastic astrocytoma. Cancer. 2008 May 1;112(9):2038-45. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Irinotecan & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Vredenburgh et al. 2007 | Not reported | Phase 2 |
Note: Vredenburgh et al. 2007 described 6-week cycles in which treatment was every 2 weeks and was otherwise identical, so its entry was consolidated with Taillibert et al. 2009.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once on day 1, given first
Targeted therapy
- Bevacizumab (Avastin) 10 mg/kg IV once on day 1, given second
- 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 therapy
- "Appropriate antiemetics"
14-day cycles
Dose and schedule modifications
- Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose of irinotecan: 340 mg/m2
References
- 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Taillibert S, Vincent LA, Granger B, Marie Y, Carpentier C, Guillevin R, Bellanger A, Mokhtari K, Rousseau A, Psimaras D, Dehais C, Sierra del Rio M, Meng Y, Laigle-Donadey F, Hoang-Xuan K, Sanson M, Delattre JY. Bevacizumab and irinotecan for recurrent oligodendroglial tumors. Neurology. 2009 May 5;72(18):1601-6. link to original article PubMed
PCV
PCV: Procarbazine, CCNU (Lomustine), Vincristine
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wick et al. 2009 (NOA-04) | 1999-2005 | Phase 3 (E-esc) | Temozolomide | Did not meet primary endpoint of TTF |
Preceding treatment
- RT or salvage temozolomide or salvage RT, with progression
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) 2 mg IV once per day on days 8 & 29
8-week cycles
Subsequent treatment
- NOA-04, upon progression, patients who had not previously received temozolomide: Salvage temozolomide
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Levin et al. 1980 | Not reported in abstract | 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 #3, higher doses
Study | Dates of enrollment | Evidence |
---|---|---|
Cairncross et al. 1994 | 1989-1992 | Phase 2 |
Chemotherapy
- Procarbazine (Matulane) 75 mg/m2 PO once per day on days 8 to 21
- Lomustine (CCNU) 130 mg/m2 PO once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once per day on days 8 & 29
42-day 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. dosing details in abstract have been reviewed by our editors PubMed
- Cairncross G, Macdonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr, Wainman N, Eisenhauer E; National Cancer Institute of Canada Clinical Trials Group. Chemotherapy for anaplastic oligodendroglioma. J Clin Oncol. 1994 Oct;12(10):2013-21. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Retrospective: Kappelle AC, Postma TJ, Taphoorn MJ, Groeneveld GJ, van den Bent MJ, van Groeningen CJ, Zonnenberg BA, Sneeuw KC, Heimans JJ. PCV chemotherapy for recurrent glioblastoma multiforme. Neurology. 2001 Jan 9;56(1):118-20. link to original article PubMed
- NOA-04: Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00717210
- Update: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. link to original article link to PMC article PubMed
Radiation therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wick et al. 2009 (NOA-04) | 1999-2005 | Phase 3 (C) | 1. PCV | Did not meet primary endpoint of TTF |
2. Temozolomide | Did not meet primary endpoint of TTF |
Preceding treatment
- Adjuvant PCV versus temozolomide, with progression
Radiotherapy
- External beam radiotherapy with 1.8 to 200 cGy fractions for a total dose of 6000 cGy
6-week course
Subsequent treatment
- NOA-04, at progression: Salvage PCV if they had previously received temozolomide or temozolomide if they had previously received PCV
References
- NOA-04: Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00717210
- Update: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. link to original article link to PMC article PubMed
Temozolomide monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wick et al. 2009 (NOA-04) | 1999-2005 | Phase 3 (E-de-esc) | PCV | Did not meet primary endpoint of TTF |
Subsequent treatment
- NOA-04, upon progression, patients who had not previously received PCV: Salvage PCV
Regimen variant #2, continuous therapy
Study | Dates of enrollment | Evidence |
---|---|---|
Perry et al. 2008 (RESCUE) | 2001-01 to 2005-07 | Retrospective |
Note: Patients who undergo conventional temozolomide therapy, have surgery and radiation therapy, and then relapse receive:
Subsequent treatment
- RESCUE, upon progression: Salvage temozolomide; 50 mg/m2 PO once per day
Regimen variant #3
Study | Dates of enrollment | Evidence |
---|---|---|
Yung et al. 1999 (MK-7365-006) | Not reported | Phase 2 (RT) |
Chemotherapy
- Temozolomide (Temodar) by the following exposure-based criteria:
- Patients who had never previously received chemotherapy: 200 mg/m2 PO once per day on days 1 to 5
- Patients who previously received chemotherapy: 150 mg/m2 PO once per day on days 1 to 5
Supportive therapy
- Prophylactic antiemetics as needed
- Lowest dose of corticosteroids necessary to maintain neurologic stability
28-day cycle for up to 26 cycles (2 years)
Dose and schedule modifications
- If tolerated in patients who previously received chemotherapy, temozolomide dose could be increased to 200 mg/m2
References
- MK-7365-006: Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman HS, Albright R, Olson J, Chang SM, O'Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA; Temodal Brain Tumor Group. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J Clin Oncol. 1999 Sep;17(9):2762-71. link to original article dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors 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 dosing details in manuscript have been reviewed by our editors PubMed
- NOA-04: Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M. NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol. 2009 Dec 10;27(35):5874-80. Epub 2009 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00717210
- Update: Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M; Neuro-oncology Working Group of the German Cancer Society. Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol. 2016 Nov;18(11):1529-1537. Epub 2016 Jul 1. Erratum in: Neuro Oncol. 2016 Nov;18(11):e1. link to original article link to PMC article PubMed