Difference between revisions of "Anaplastic glioma"

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'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
 
'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
  
−
Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].
+
Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].
  
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
−
|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
+
|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
−
<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
+
<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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|-
 
|-
 
|}
 
|}
−
 
+
====Chemotherapy====
−
*[[Procarbazine (Matulane)]] 60 mg/m2 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 (Ceenu)]] 110 mg/m2 PO once on day 1
+
*[[Lomustine (Ceenu)]] 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 x 4 cycles'''
+
'''8-week cycle for 4 cycles'''
  
 
''Patients with stable disease or better received '''2 more cycles of PCV'''. At time of disease progression patients proceeded to receive [[#Radiation_therapy_2|radiation therapy]].''
 
''Patients with stable disease or better received '''2 more cycles of PCV'''. At time of disease progression patients proceeded to receive [[#Radiation_therapy_2|radiation therapy]].''
Line 88: Line 88:
  
 
''Adjuvant radiation alone; used as a comparator arm in the referenced trials.''
 
''Adjuvant radiation alone; used as a comparator arm in the referenced trials.''
−
 
+
====Radiotherapy====
 
*Radiation therapy with 1.8 to 2 Gy fractions given over 6 weeks for a total dose of 60 Gy
 
*Radiation therapy with 1.8 to 2 Gy fractions given over 6 weeks for a total dose of 60 Gy
  
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|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
*Regimen is the same as [[#Radiation_.26_Carmustine_.28BiCNU.29_2|Radiation & Carmustine (BiCNU) adjuvant regimen in Glioblastoma multiforme, Shapiro et al. 1989]]
+
===Regimen {{#subobject:31c739|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://thejns.org/doi/abs/10.3171/jns.1989.71.1.0001 Shapiro et al. 1989 (BTCG 8001)]
 +
|<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
|Carmustine/Procarbazine & RT<br> Carmustine & Hydrea/Procarbazine & VM-26 & RT
 +
|-
 +
|}
 +
 
 +
====Radiotherapy====
 +
*Radiation therapy starting within 3 weeks after surgical resection, with one of the following:
 +
**Whole brain: 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
 +
**Whole brain & cone down: 172 cGy (rads) fractions x 25 fractions, given over 5 weeks for a total dose of 4300 cGy (4300 rads), then coned-down boost of 172 cGy (rads) fractions x 10 fractions, given over 2 weeks for a dose of 1720 cGy (rads), and a total cumulative dose of 6020 cGy (rads)
 +
 
 +
''One course, followed by:''
 +
====Chemotherapy====
 +
*[[Carmustine (BiCNU)]] 80 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 3
 +
 
 +
'''8-week cycles, with no more than a maximum total dose of 1500 mg/m<sup>2</sup> [[Carmustine (BiCNU)]] given'''
 +
 
 +
Supportive care:
 +
*Pulmonary function tests (PFTs) checked before start of therapy, and then when cumulative dose of [[Carmustine (BiCNU)]] reaches 800 mg/m<sup>2</sup> and 1200 mg/m<sup>2</sup>
 +
 
 +
===References===
 +
# Shapiro WR, Green SB, Burger PC, Mahaley MS Jr, Selker RG, VanGilder JC, Robertson JT, Ransohoff J, Mealey J Jr, Strike TA et al. 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. [http://thejns.org/doi/abs/10.3171/jns.1989.71.1.0001 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/2661738 PubMed]
  
 
==RT -> PCV {{#subobject:1097a5|Regimen=1}}==
 
==RT -> PCV {{#subobject:1097a5|Regimen=1}}==
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|}
 
|}
  
−
''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:''
−
*Radiation therapy with either:
+
====Radiotherapy====
 +
*Either:
 
**2.25 Gy fractions x 20 fractions, given 5 days per week over 4 weeks, total dose of 45 Gy
 
**2.25 Gy fractions x 20 fractions, given 5 days per week over 4 weeks, total dose of 45 Gy
 
**or 2 Gy fractions x 30 fractions, given 5 days per week over 6 weeks, total dose of 60 Gy
 
**or 2 Gy fractions x 30 fractions, given 5 days per week over 6 weeks, total dose of 60 Gy
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''Chemotherapy begins 3 to 4 weeks after completion of radiation therapy:''
 
''Chemotherapy begins 3 to 4 weeks after completion of radiation therapy:''
  
−
*[[Procarbazine (Matulane)]] 100 mg/m2 PO once per day on days 1 to 10
+
====Chemotherapy====
−
*[[Lomustine (Ceenu)]] 100 mg/m2 PO once on day 1
+
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 10
−
*[[Vincristine (Oncovin)]] 1.5 mg/m2 (maximum dose of 2 mg) IV fast infusion once on day 1
+
*[[Lomustine (Ceenu)]] 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 fast infusion once on day 1
  
−
'''6-week cycle x up to 12 cycles'''
+
====Supportive medications====
 +
*[[: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.
  
−
Supportive medications:
+
'''6-week cycle for up to 12 cycles'''
−
*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.
 
  
 
===Regimen #2 {{#subobject:75fc7d|Variant=1}}===
 
===Regimen #2 {{#subobject:75fc7d|Variant=1}}===
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''Radiation therapy starts within 6 weeks after surgery.''
 
''Radiation therapy starts within 6 weeks after surgery.''
 +
====Radiotherapy====
 
*Radiation therapy, 1.8 Gy fractions x 25 fractions, given 5 days per week, total dose of 45 Gy to the planning target volume (PTV-1); then a boost of 1.8 Gy fractions x 8 fractions, given 5 days per week, total boost dose of 14.4 Gy to the PTV-2, for a total cumulative dose of 59.4 Gy
 
*Radiation therapy, 1.8 Gy fractions x 25 fractions, given 5 days per week, total dose of 45 Gy to the planning target volume (PTV-1); then a boost of 1.8 Gy fractions x 8 fractions, given 5 days per week, total boost dose of 14.4 Gy to the PTV-2, for a total cumulative dose of 59.4 Gy
  
 
''Chemotherapy begins within 4 weeks after completion of radiation therapy:''
 
''Chemotherapy begins within 4 weeks after completion of radiation therapy:''
  
−
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day on days 8 to 21
+
====Chemotherapy====
−
*[[Lomustine (Ceenu)]] 110 mg/m2 PO once on day 1
+
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 8 & 29
+
*[[Lomustine (Ceenu)]] 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
  
−
'''6-week cycle x 6 cycles'''
+
====Supportive medications====
 +
*Antiemetics for [[Lomustine (Ceenu)]]: "[[Domperidone (Motilium)]] or [[Metoclopramide (Reglan)]], and if necessary, [[Ondansetron (Zofran)]] or a similar agent"
 +
*[[:Category:Steroids|Corticosteroids]] kept at lowest possible dose
  
−
Supportive medications:
+
'''6-week cycle for 6 cycles'''
−
*Antiemetics for lomustine: "domperidone or metoclopramide, and if necessary, ondansetron or a similar agent"
 
−
*[[Steroid conversions|Corticosteroids]] kept at lowest possible dose
 
  
 
===References===
 
===References===
Line 207: Line 243:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
'''28-day cycle for 8 cycles'''
−
 
 
−
'''28-day cycle x 8 cycles'''
 
  
 
''Patients with stable disease or better received '''4 more cycles of temozolomide'''. At time of disease progression patients proceeded to receive [[#Radiation_therapy_2|radiation therapy]].''
 
''Patients with stable disease or better received '''4 more cycles of temozolomide'''. At time of disease progression patients proceeded to receive [[#Radiation_therapy_2|radiation therapy]].''
Line 230: Line 266:
  
 
''This regimen is meant for patients with 1p/19q loss of heterozygosity (LOH).''
 
''This regimen is meant for patients with 1p/19q loss of heterozygosity (LOH).''
−
 
+
====Chemotherapy====
 
*[[Temozolomide (Temodar)]] as follows:
 
*[[Temozolomide (Temodar)]] as follows:
−
**Cycles 1 & 2: 150 mg/m2 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, on empty stomach
−
**Cycle 3 onwards (if no myelosuppression): 200 mg/m2 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, on empty stomach
  
 
'''28-day cycles'''
 
'''28-day cycles'''
  
−
===Regimen #3, Taliansky-Aronov et al. 2006 {{#subobject:f096ab|Variant=1}}===
+
===Regimen #3 {{#subobject:f096ab|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.springerlink.com/content/jnn8w15613880103 Taliansky-Aronov et al. 2006]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
====Supportive medications====
 +
*[[:Category:Steroids|Corticosteroids]] could be continued at same dose or reduced, but not increased while on study
  
 
'''28-day cycles, given until progression of disease or, in patients with stable disease, up to 24 months'''
 
'''28-day cycles, given until progression of disease or, in patients with stable disease, up to 24 months'''
−
 
−
Supportive medications:
 
−
*Corticosteroids could be continued at same dose or reduced, but not increased while on study
 
  
 
===References===
 
===References===
Line 280: Line 322:
  
 
''This regimen is meant for patients without 1p/19q loss of heterozygosity (LOH).''
 
''This regimen is meant for patients without 1p/19q loss of heterozygosity (LOH).''
−
 
+
====Chemotherapy====
 
*[[Temozolomide (Temodar)]] as follows:
 
*[[Temozolomide (Temodar)]] as follows:
−
**Cycles 1 & 2: 150 mg/m2 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, on empty stomach
−
**Cycle 3 onwards (if no myelosuppression): 200 mg/m2 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, on empty stomach
  
−
'''28-day cycle x 2 to 4 cycles, followed by:'''
+
'''28-day cycle for 2 to 4 cycles, followed by:'''
  
 +
====Chemoradiotherapy====
 +
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day during radiation therapy
 
*Concurrent radiation therapy with a total dose of 60 Gy
 
*Concurrent radiation therapy with a total dose of 60 Gy
−
*[[Temozolomide (Temodar)]] 75 mg/m2 PO once per day during radiation therapy
 
  
−
'''Radiation therapy followed by:'''
+
'''One course, followed by:'''
−
*[[Temozolomide (Temodar)]] 150 to 200 mg/m2 PO once per day on days 1 to 5, on empty stomach
+
 
 +
====Chemotherapy====
 +
*[[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'''
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|}
 
|}
 
===Regimen {{#subobject:a83fc7|Variant=1}}===
 
===Regimen {{#subobject:a83fc7|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.springerlink.com/content/7081r46v63261jm4 Chamberlain et al. 2008]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 312: Line 361:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[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 medications====
 +
*Use of [[:Category:Steroids|steroids]] allowed for control of neurologic signs and symptoms
  
 
'''14-day cycles'''
 
'''14-day cycles'''
−
 
−
Supportive medications:
 
−
*Use of [[Steroid conversions|steroids]] allowed for control of neurologic signs and symptoms
 
  
 
===References===
 
===References===
 
# 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. [http://www.springerlink.com/content/7081r46v63261jm4 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18953491 PubMed]  
 
# 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. [http://www.springerlink.com/content/7081r46v63261jm4 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18953491 PubMed]  
−
# Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009 Apr 15;115(8):1734-43. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24179/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19197992 PubMed]
+
# '''Retrospective:''' Chamberlain MC, Johnston S. Bevacizumab for recurrent alkylator-refractory anaplastic oligodendroglioma. Cancer. 2009 Apr 15;115(8):1734-43. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.24179/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19197992 PubMed]
  
 
==Bevacizumab & Carboplatin {{#subobject:35870a|Regimen=1}}==
 
==Bevacizumab & Carboplatin {{#subobject:35870a|Regimen=1}}==
Line 329: Line 380:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
*Regimen is the same as [[#Carboplatin_.28Paraplatin.29_.26_Bevacizumab_.28Avastin.29_2|Carboplatin (Paraplatin) & Bevacizumab (Avastin) salvage therapy in glioblastoma multiforme, Regimen #1, Thompson et al. 2010 and Regimen #2, Norden et al. 2008]]
+
===Regimen #1 {{#subobject:419b2e|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://journals.lww.com/neurosurgery/pages/articleviewer.aspx?year=2010&issue=07000&article=00013&type=abstract Thompson et al. 2010]
 +
|<span
 +
style="background:#ff0000;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Retrospective</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
 
 +
'''28-day cycles'''
 +
 
 +
===Regimen #2 {{#subobject:fe380b|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.neurology.org/content/70/10/779.long Norden et al. 2008]
 +
|<span
 +
style="background:#ff0000;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Retrospective</span>
 +
|-
 +
|}
 +
 
 +
====Chemotherapy====
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 +
*[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV (reference does not list schedule of carboplatin)
 +
 
 +
===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. [http://www.neurology.org/content/70/10/779.long link to original article]  [http://www.ncbi.nlm.nih.gov/pubmed/18316689 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. [http://journals.lww.com/neurosurgery/pages/articleviewer.aspx?year=2010&issue=07000&article=00013&type=abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20559095 PubMed]
  
 
==Bevacizumab & Irinotecan {{#subobject:6cc49b|Regimen=1}}==
 
==Bevacizumab & Irinotecan {{#subobject:6cc49b|Regimen=1}}==
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|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
''These regimens are essentially the same as [[#Irinotecan_.28Camptosar.29_.26_Bevacizumab_.28Avastin.29_2|Irinotecan (Camptosar) & Bevacizumab (Avastin) salvage therapy in glioblastoma multiforme, Regimen #1, Chen et al. 2007, Vredenburgh et al. 2007, Norden et al. 2008 - every 2 week schedule]].''
 
−
 
 
===Regimen {{#subobject:b04dbd|Variant=1}}===
 
===Regimen {{#subobject:b04dbd|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/13/4/1253.long Vredenburgh et al. 2007]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 346: Line 440:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
 
+
|-
−
*[[Irinotecan (Camptosar)]] 125 mg/m2 IV once on day 1, given first, over 90 minutes before the start of bevacizumab
+
|}
−
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: [[Irinotecan (Camptosar)]] 340 mg/m2 IV once on day 1, given first, over 90 minutes before the start of bevacizumab
+
''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.''
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1, given second, after irinotecan
+
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
 +
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 340 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1, '''given second'''
 
**Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later  
 
**Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later  
  
−
'''14-day cycles'''; 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
+
====Supportive medications====
 +
*"Appropriate antiemetics"
  
−
Supportive medications:
+
'''14-day cycles'''
−
*"Appropriate antiemetics"
 
  
 
===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. [http://clincancerres.aacrjournals.org/content/13/4/1253.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://clincancerres.aacrjournals.org/content/13/4/1253.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17317837 PubMed]
−
# 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. [http://www.neurology.org/content/72/18/1601.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.neurology.org/content/72/18/1601.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19414728 PubMed]
  
 
==Cyclophosphamide (Cytoxan) {{#subobject:270740|Regimen=1}}==
 
==Cyclophosphamide (Cytoxan) {{#subobject:270740|Regimen=1}}==
Line 367: Line 464:
 
|}
 
|}
 
===Regimen {{#subobject:cd7eda|Variant=1}}===
 
===Regimen {{#subobject:cd7eda|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.21582/full Chamberlain et al. 2006]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 374: Line 475:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2
  
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 30 minutes once per day on days 1 & 2
+
====Supportive medications====
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
Supportive medications:
 
 
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms
 
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms
−
*Ondansetron (Zofran) 0.15 mg/kg IV once prior to cyclophosphamide
+
*[[Ondansetron (Zofran)]] 0.15 mg/kg IV once prior to cyclophosphamide
 
*[[Dexamethasone (Decadron)]] 4 mg IV once prior to cyclophosphamide
 
*[[Dexamethasone (Decadron)]] 4 mg IV once prior to cyclophosphamide
 
*1 liter normal saline IV over 2 hours prior to cyclophosphamide
 
*1 liter normal saline IV over 2 hours prior to cyclophosphamide
−
*Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
+
*[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting
 +
 
 +
'''28-day cycles'''
  
 
===References===
 
===References===
Line 395: Line 498:
 
|}
 
|}
 
===Regimen {{#subobject:9960a7|Variant=1}}===
 
===Regimen {{#subobject:9960a7|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://link.springer.com/article/10.1007/BF00177478 Fulton et al. 1996]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 402: Line 509:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
 
+
|-
 +
|}
 +
====Chemotherapy====
 
*[[Etoposide (Vepesid)]] 50 mg PO once per day
 
*[[Etoposide (Vepesid)]] 50 mg PO once per day
  
−
'''given until progression of disease or unacceptable toxicity'''
+
'''Given until progression of disease or unacceptable toxicity'''
  
 
===References===
 
===References===
Line 415: Line 524:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
''Another regimen can be found under [[#Irinotecan_.28Camptosar.29_2|Irinotecan (Camptosar) salvage therapy in glioblastoma multiforme, Friedman et al. 1999]].''
 
  
−
===Regimen {{#subobject:31e6bc|Variant=1}}===
+
===Regimen #1 {{#subobject:31e6bc|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23404/full Chamberlain et al. 2008]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 425: Line 537:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV over 120 minutes once on day 1
 +
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 600 mg/m<sup>2</sup> IV over 120 minutes once on day 1
  
−
*[[Irinotecan (Camptosar)]] 350 mg/m2 IV over 120 minutes once on day 1
+
====Supportive medications====
−
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: [[Irinotecan (Camptosar)]] 600 mg/m2 IV over 120 minutes once on day 1
+
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms
 +
*500 mL normal saline IV over 1 hour prior to irinotecan
 +
*Intravenous [[Ondansetron (Zofran)]], [[Granisetron (Kytril)]], or [[Dolasetron (Anzemet)]] as [[Antiemesis|antiemetic]] prior to irinotecan
 +
*[[Dexamethasone (Decadron)]] 20 mg IV once prior to irinotecan
 +
*[[Atropine (Atropen)]] 0.5 mg IV once prior to irinotecan
 +
*[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting
 +
*[[Loperamide (Imodium)]] (dose/schedule not specified) prn diarrhea
  
 
'''21-day cycles'''
 
'''21-day cycles'''
  
−
Supportive medications:
+
===Regimen #2 {{#subobject:2512a2|Variant=1}}===
−
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms
+
{| border="1" style="text-align:center;" !align="left"
−
*500 mL normal saline IV over 1 hour prior to irinotecan
+
|'''Study'''
−
*Intravenous ondansetron (Zofran), granisetron (Kytril), or dolasetron (Anzemet) as [[Antiemesis|antiemetic]] prior to irinotecan
+
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
−
*[[Dexamethasone (Decadron)]] 20 mg IV once prior to irinotecan
+
|-
−
*Atropine 0.5 mg IV once prior to irinotecan
+
|[http://jco.ascopubs.org/content/17/5/1516.long Friedman et al. 1999]
−
*Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
+
|<span
−
*Loperamide (Imodium) (dose/schedule not specified) prn diarrhea
+
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
**If tolerated, dose could be increased to 150 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
 
 +
====Supportive medications====
 +
*[[Steroid conversions|Steroids]] at lowest dose necessary
 +
*Avoid laxatives and magnesium-containing antacids due to potential for diarrhea
 +
 
 +
'''42-day (6-week) cycles, given until progression of disease or unacceptable toxicity'''
  
 
===References===
 
===References===
−
# Chamberlain MC. Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol. 2002 Sep;59(2):157-63. [http://link.springer.com/article/10.1023/A%3A1019608404378 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12241109 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. [http://jco.ascopubs.org/content/17/5/1516.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10334539 PubMed]
 +
# '''Phase I:''' Chamberlain MC. Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol. 2002 Sep;59(2):157-63. [http://link.springer.com/article/10.1023/A%3A1019608404378 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12241109 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23404/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23404/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18361434 PubMed]
  
Line 449: Line 588:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
*Note: The NCCN, Central Nervous System Cancers version 1.2013 lists this regimen (Wick et al. 2010) with [[#Lomustine_.28Ceenu.29_2|Lomustine (Ceenu) salvage therapy in glioblastoma multiforme]] as an option for treatment of anaplastic gliomas. This study only included patients who had histologically confirmed WHO grade 4 glioblastoma. The NCCN also listed the following phase II trial as a reference for use of Carmustine (BiCNU)/Lomustine (Ceenu) in recurrent malignant glioma, but the nitrosourea used was fotemustine (FTM): R. Soffietti, R. Rudà, E. Trevisan, E. Picco, D. Guarneri, M. Caroli, M. Fabrini, V. Scotti. Phase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: A multicenter Italian study. CNS Tumors 2012 J Clin Oncol 27:15s, 2009 (suppl; abstr 2012). 2009 ASCO Annual Meeting abstract 2012. [https://meetinglibrary.asco.org/content/32821-65 link to abstract]
+
*Note: The NCCN, Central Nervous System Cancers version 1.2013 lists this regimen (Wick et al. 2010) with [[#Lomustine_.28Ceenu.29_2|Lomustine (Ceenu) salvage therapy in glioblastoma multiforme]] as an option for treatment of anaplastic gliomas. This study only included patients who had histologically confirmed WHO grade 4 glioblastoma. The NCCN also listed the following phase II trial as a reference for use of Carmustine (BiCNU)/Lomustine (Ceenu) in recurrent malignant glioma, but the nitrosourea used was fotemustine (FTM): R. Soffietti, R. Rudà, E. Trevisan, E. Picco, D. Guarneri, M. Caroli, M. Fabrini, V. Scotti. Phase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: A multicenter Italian study. CNS Tumors 2012 J Clin Oncol 27:15s, 2009 (suppl; abstr 2012). 2009 ASCO Annual Meeting abstract 2012. [https://meetinglibrary.asco.org/content/32821-65 link to abstract]
  
 
==PCV {{#subobject:1d08ed|Regimen=1}}==
 
==PCV {{#subobject:1d08ed|Regimen=1}}==
Line 475: Line 614:
 
|}
 
|}
 
''All patients had progressed after previously receiving [[#Radiation_therapy|radiation therapy]], [[#Temozolomide_.28Temodar.29_2|salvage temozolomide]], or [[#Radiation_therapy_2|salvage radiation therapy]].''
 
''All patients had progressed after previously receiving [[#Radiation_therapy|radiation therapy]], [[#Temozolomide_.28Temodar.29_2|salvage temozolomide]], or [[#Radiation_therapy_2|salvage radiation therapy]].''
−
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day on days 8 to 21
+
====Chemotherapy====
−
*[[Lomustine (Ceenu)]] 110 mg/m2 PO once on day 1
+
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21
 +
*[[Lomustine (Ceenu)]] 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
  
Line 483: Line 623:
 
''At progression, patients who had not previously received temozolomide proceeded to receive [[#Temozolomide_.28Temodar.29_2|salvage temozolomide]].''
 
''At progression, patients who had not previously received temozolomide proceeded to receive [[#Temozolomide_.28Temodar.29_2|salvage temozolomide]].''
  
−
===Regimen #1, Levin et al. 1980 {{#subobject:d8f8c2|Variant=1}}===
+
===Regimen #2 {{#subobject:d8f8c2|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.ncbi.nlm.nih.gov/pubmed/7407756 Levin et al. 1980]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 491: Line 635:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
−
 
+
|-
−
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day on days 8 to 21
+
|}
−
*[[Lomustine (Ceenu)]] 110 mg/m2 PO once on day 1
+
====Chemotherapy====
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 8 & 29
+
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21
 +
*[[Lomustine (Ceenu)]] 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
  
 
'''6-week cycles, given until progression of disease or unacceptable toxicity'''
 
'''6-week cycles, given until progression of disease or unacceptable toxicity'''
  
−
===Regimen #2, Cairncross et al. 1994 - higher doses {{#subobject:eacf9b|Variant=1}}===
+
===Regimen #3, higher doses {{#subobject:eacf9b|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/12/10/2013.long Cairncross et al. 1994]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 506: Line 656:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
 
+
|-
−
*[[Procarbazine (Matulane)]] 75 mg/m2 PO once per day on days 8 to 21
+
|}
−
*[[Lomustine (Ceenu)]] 130 mg/m2 PO once on day 1
+
====Chemotherapy====
−
*[[Vincristine (Oncovin)]] 1.4 mg/m2 (dose not capped) IV once per day on days 8 & 29
+
*[[Procarbazine (Matulane)]] 75 mg/m<sup>2</sup> PO once per day on days 8 to 21
 +
*[[Lomustine (Ceenu)]] 130 mg/m<sup>2</sup> PO once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (dose not capped) IV once per day on days 8 & 29
  
 
'''6-week cycles, given until progression of disease or unacceptable toxicity'''
 
'''6-week cycles, given until progression of disease or unacceptable toxicity'''
Line 543: Line 695:
  
 
''Patients had previously received [[#PCV|PCV]] versus [[#Temozolomide_.28Temodar.29|temozolomide]] prior to progression.''
 
''Patients had previously received [[#PCV|PCV]] versus [[#Temozolomide_.28Temodar.29|temozolomide]] prior to progression.''
−
 
+
====Radiotherapy====
 
*Radiation therapy with 1.8 to 2 Gy fractions given over 6 weeks for a total dose of 60 Gy
 
*Radiation therapy with 1.8 to 2 Gy fractions given over 6 weeks for a total dose of 60 Gy
  
Line 574: Line 726:
 
|}
 
|}
 
''All patients had progressed after previously receiving [[#Radiation_therapy|radiation therapy]], [[#PCV_2|salvage PCV]], or [[#Radiation_therapy_2|salvage radiation therapy]].''
 
''All patients had progressed after previously receiving [[#Radiation_therapy|radiation therapy]], [[#PCV_2|salvage PCV]], or [[#Radiation_therapy_2|salvage radiation therapy]].''
−
 
+
====Chemotherapy====
−
*[[Temozolomide (Temodar)]] 200 mg/m2 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 until progression'''
 
'''28-day cycles until progression'''
Line 581: Line 733:
 
''At progression, patients who had not previously received PCV proceeded to receive [[#PCV_2|salvage PCV]].''
 
''At progression, patients who had not previously received PCV proceeded to receive [[#PCV_2|salvage PCV]].''
  
−
===Regimen #2, Perry et al. 2008 & Perry et al. 2010 - continuous therapy; RESCUE study {{#subobject:276de1|Variant=1}}===
+
===Regimen #2, continuous therapy {{#subobject:276de1|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full Perry et al. 2008 (RESCUE)]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 589: Line 745:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
''Patients who undergo conventional temozolomide therapy, have surgery and radiation therapy, and then relapse receive:''
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 150 to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
Patients who undergo conventional temozolomide therapy, have surgery and radiation therapy, and then relapse receive:
+
'''28-day cycles'''
−
*[[Temozolomide (Temodar)]] 150 to 200 mg/m2 PO once per day on days 1 to 5
 
  
−
'''28-day cycles'''
+
''Patients with progressive disease are changed to:''
 +
*[[Temozolomide (Temodar)]] 50 mg/m<sup>2</sup> PO once per day, taken continuously without treatment break
  
−
Patients with progressive disease are changed to:
+
'''Given until progression of disease or unacceptable toxicity'''
−
*[[Temozolomide (Temodar)]] 50 mg/m2 PO once per day, taken continuously without treatment break
 
  
−
'''given until progression of disease or unacceptable toxicity'''
+
===Regimen #3, traditional dosing {{#subobject:1839a1|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full Nicholson et al. 2007]
 +
|<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
**Patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
===Regimen #3, Nicholson et al. 2007 - traditional dosing {{#subobject:1839a1|Variant=1}}===
+
'''28-day cycle for up to 11 cycles'''
−
*Regimen is the same as [[#Temozolomide_.28Temodar.29_5|Temozolomide (Temodar) in supratentorial astrocytoma or oligodendroglioma recurrent disease, Regimen #4, Nicholson et al. 2007 - traditional dosing]]
 
  
−
===Regimen #4, Yung et al. 1999 {{#subobject:52f20c|Variant=1}}===
+
===Regimen #4 {{#subobject:52f20c|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/17/9/2762.long Yung et al. 1999]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 611: Line 790:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
  
−
*Patients who had never previously received chemotherapy: [[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
====Chemotherapy====
−
*Patients who previously received chemotherapy started with [[Temozolomide (Temodar)]] 150 mg/m2 PO once per day on days 1 to 5, which could be increased as tolerated to [[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
*[[Temozolomide (Temodar)]] as follows:
−
 
+
**Patients who had never previously received chemotherapy: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
−
'''28-day cycles x up to 2 years'''
+
**Patients who previously received chemotherapy started with 150 mg/m<sup>2</sup> PO once per day on days 1 to 5, which could be increased as tolerated to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*Prophylactic [[antiemesis|antiemetics]] as needed
 
*Prophylactic [[antiemesis|antiemetics]] as needed
 
*Lowest dose of [[Steroid conversions|corticosteroids]] necessary to maintain neurologic stability
 
*Lowest dose of [[Steroid conversions|corticosteroids]] necessary to maintain neurologic stability
 +
 +
'''28-day cycle for up to 2 years'''
  
 
===References===
 
===References===
 
# 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. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999 Sep;17(9):2762-71. [http://jco.ascopubs.org/content/17/9/2762.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999 Sep;17(9):2762-71. [http://jco.ascopubs.org/content/17/9/2762.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10561351 PubMed]
 +
# Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17705175 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18756530 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18756530 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. [http://jco.ascopubs.org/content/28/12/2051.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/28/12/2051.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20308655 PubMed]
Line 679: Line 863:
 
|}
 
|}
  
 +
====Radiotherapy====
 
*Radiation therapy starting within 3 weeks after surgical resection, with one of the following:
 
*Radiation therapy starting within 3 weeks after surgical resection, with one of the following:
 
**Whole brain: 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
 
**Whole brain: 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
 
**Whole brain & cone down: 172 cGy (rads) fractions x 25 fractions, given over 5 weeks for a total dose of 4300 cGy (4300 rads), then coned-down boost of 172 cGy (rads) fractions x 10 fractions, given over 2 weeks for a dose of 1720 cGy (rads), and a total cumulative dose of 6020 cGy (rads)
 
**Whole brain & cone down: 172 cGy (rads) fractions x 25 fractions, given over 5 weeks for a total dose of 4300 cGy (4300 rads), then coned-down boost of 172 cGy (rads) fractions x 10 fractions, given over 2 weeks for a dose of 1720 cGy (rads), and a total cumulative dose of 6020 cGy (rads)
  
−
Then proceed to adjuvant chemotherapy:
+
''One course, followed by:''
−
*[[Carmustine (BiCNU)]] 80 mg/m2 IV over 30 to 60 minutes once per day on days 1 to 3
+
====Chemotherapy====
 +
*[[Carmustine (BiCNU)]] 80 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 3
  
−
'''8-week cycles, with no more than a maximum total dose of 1500 mg/m2 [[Carmustine (BiCNU)]] given'''
+
'''8-week cycles, with no more than a maximum total dose of 1500 mg/m<sup>2</sup> [[Carmustine (BiCNU)]] given'''
  
 
Supportive care:
 
Supportive care:
−
*Pulmonary function tests (PFTs) checked before start of therapy, and then when cumulative dose of [[Carmustine (BiCNU)]] reaches 800 mg/m2 and 1200 mg/m2
+
*Pulmonary function tests (PFTs) checked before start of therapy, and then when cumulative dose of [[Carmustine (BiCNU)]] reaches 800 mg/m<sup>2</sup> and 1200 mg/m<sup>2</sup>
  
 
===References===
 
===References===
Line 733: Line 919:
 
|-
 
|-
 
|}
 
|}
−
 
+
====Chemoradiotherapy====
−
====Chemoradiation====
+
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days
 
*Concurrent radiation therapy, 2 Gy fractions x 30 fractions given 5 days per week, for a total dose of 60 Gy
 
*Concurrent radiation therapy, 2 Gy fractions x 30 fractions given 5 days per week, for a total dose of 60 Gy
−
*[[Temozolomide (Temodar)]] 75 mg/m2 PO once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days
 
  
−
Supportive medications:
+
====Supportive medications====
 
*PCP prophylaxis with one of the following:
 
*PCP prophylaxis with one of the following:
 
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
 
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
Line 750: Line 935:
 
====Chemotherapy====
 
====Chemotherapy====
 
*[[Temozolomide (Temodar)]] as follows:
 
*[[Temozolomide (Temodar)]] as follows:
−
**Cycle 1: 150 mg/m2 PO once per day on days 1 to 5  
+
**Cycle 1: 150 mg/m<sup>2</sup> PO once per day on days 1 to 5  
−
**If tolerated, in cycles 2 to 6: 200 mg/m2 PO once per day on days 1 to 5
+
**If tolerated, in cycles 2 to 6: 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
Supportive medications:
+
====Supportive medications====
 
*[[Metoclopramide (Reglan)]] or [[Antiemesis|5-HT3 antagonist]] required
 
*[[Metoclopramide (Reglan)]] or [[Antiemesis|5-HT3 antagonist]] required
  
−
'''28-day cycle x 6 cycles'''
+
'''28-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 770: Line 955:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen #1, Friedman et al. 2009 {{#subobject:c6f29b|Variant=1}}===
+
===Regimen #1 {{#subobject:c6f29b|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
−
style="background:#EEEE00;
+
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/27/28/4733.long Friedman et al. 2009]
 +
|<span  
 +
style="background:#00cd00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
 
border-color:black;
 
border-color:black;
 
border-width:2px;
 
border-width:2px;
−
border-style:solid;">Phase II</span>
+
border-style:solid;">Randomized Phase II</span>
−
 
+
|[[#Bevacizumab_.26_Irinotecan_2|Bevacizumab & Irinotecan]]
 +
|-
 +
|}
 +
====Chemotherapy====
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1, 15, 29
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1, 15, 29
  
−
'''6-week cycles x up to 104 weeks, until progression of disease, or unacceptable toxicity'''
+
'''6-week cycle for up to 104 weeks, until progression of disease, or unacceptable toxicity'''
  
−
===Regimen #2, Kreisl et al. 2009 {{#subobject:35ed36|Variant=1}}===
+
===Regimen #2 {{#subobject:35ed36|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/27/5/740.long Kreisl et al. 2008]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 791: Line 988:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
 
+
|-
 +
|}
 +
====Chemotherapy====
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1 & 15
  
−
'''4-week cycles, given until progression of disease, or unacceptable toxicity'''; upon progression, patients received [[#Irinotecan_.28Camptosar.29_.26_Bevacizumab_.28Avastin.29_2|Irinotecan (Camptosar) & Bevacizumab (Avastin)]]
+
'''4-week cycles, given until progression of disease, or unacceptable toxicity'''; upon progression, patients received [[#Irinotecan_.28Camptosar.29_.26_Bevacizumab_.28Avastin.29_2|Irinotecan (Camptosar) & Bevacizumab (Avastin)]]
  
 
===References===
 
===References===
−
# Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. doi: 10.1200/JCO.2008.16.3055. Epub 2008 Dec 29. [http://jco.ascopubs.org/content/27/5/740.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19114704 PubMed]
+
# Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. Epub 2008 Dec 29. [http://jco.ascopubs.org/content/27/5/740.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19114704 PubMed]
 +
<!-- Presented in part at the 12th Annual Meeting of the Society for Neuro-Oncology, November 15-18, 2007, Dallas, TX, and at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
 
# Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4733.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720927 PubMed]
 
# Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4733.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720927 PubMed]
  
Line 805: Line 1,005:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen #1, Thompson et al. 2010 {{#subobject:401e2e|Variant=1}}===
+
===Regimen #1 {{#subobject:401e2e|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://journals.lww.com/neurosurgery/pages/articleviewer.aspx?year=2010&issue=07000&article=00013&type=abstract Thompson et al. 2010]
 +
|<span  
 
style="background:#ff0000;
 
style="background:#ff0000;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 813: Line 1,017:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Retrospective</span>
 
border-style:solid;">Retrospective</span>
−
 
+
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 
  
 
'''28-day cycles'''  
 
'''28-day cycles'''  
  
−
===Regimen #2, Norden et al. 2008 {{#subobject:ffa90b|Variant=1}}===
+
===Regimen #2 {{#subobject:ffa90b|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.neurology.org/content/70/10/779.long Norden et al. 2008]
 +
|<span  
 
style="background:#ff0000;
 
style="background:#ff0000;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 827: Line 1,037:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Retrospective</span>
 
border-style:solid;">Retrospective</span>
 +
|-
 +
|}
  
−
*[[Carboplatin (Paraplatin)]] AUC 5-6 IV (reference does not list schedule of carboplatin)
+
====Chemotherapy====
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once every 2 weeks
 +
*[[Carboplatin (Paraplatin)]] AUC 5 to 6 IV (reference does not list schedule of carboplatin)
  
 
===References===
 
===References===
−
# 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. [http://www.neurology.org/content/70/10/779.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.neurology.org/content/70/10/779.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/18316689 PubMed]
−
# Thompson EM, Dosa E, Kraemer DF, Neuwelt EA. Treatment with bevacizumab plus carboplatin for recurrent malignant glioma. Neurosurgery. 2010 Jul;67(1):87-93. [http://journals.lww.com/neurosurgery/pages/articleviewer.aspx?year=2010&issue=07000&article=00013&type=abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://journals.lww.com/neurosurgery/pages/articleviewer.aspx?year=2010&issue=07000&article=00013&type=abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20559095 PubMed]
  
 
==Bevacizumab & Irinotecan {{#subobject:a9cf4a|Regimen=1}}==
 
==Bevacizumab & Irinotecan {{#subobject:a9cf4a|Regimen=1}}==
Line 840: Line 1,053:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen #1, Chen et al. 2007; Vredenburgh et al. 2007; Norden et al. 2008; Friedman et al. 2009 - every 2 week schedule {{#subobject:a156f1|Variant=1}}===
+
===Regimen #1, every 2 week schedule {{#subobject:a156f1|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
−
style="background:#EEEE00;
+
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/25/30/4714.long Chen et al. 2007]
 +
|<span
 +
style="background:#eeee00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Pilot, >20 pts</span>
 +
|
 +
|-
 +
|[http://jco.ascopubs.org/content/25/30/4722.long Vredenburgh et al. 2007]
 +
|<span
 +
style="background:#eeee00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
|
 +
|-
 +
|[http://www.neurology.org/content/70/10/779.long Norden et al. 2008]
 +
|<span  
 +
style="background:#eeee00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
 
border-color:black;
 
border-color:black;
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|
 +
|-
 +
|[http://jco.ascopubs.org/content/27/28/4733.long Friedman et al. 2009]
 +
|<span
 +
style="background:#00cd00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Randomized Phase II</span>
 +
|[[#Bevacizumab_.28Avastin.29_2|Bevacizumab]]
 +
|-
 +
|}
  
−
*[[Irinotecan (Camptosar)]] 125 mg/m2 IV over 90 minutes once on day 1, given first, before bevacizumab
+
''Note: Friedman et al. 2009 described 6-week cycles in which treatment was every 2 weeks, given up to 104 weeks, and was otherwise identical, so its entry was consolidated with the other ones here.''
−
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: [[Irinotecan (Camptosar)]] 340 mg/m2 (Vredenburgh et al. 2007 & Norden et al. 2008) or 350 mg/m2 (Chen et al. 2007) IV over 90 minutes once on day 1 given first, before bevacizumab
+
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1, given second, 90 minutes after the start of irinotecan
+
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
 +
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 340 mg/m<sup>2</sup> (Vredenburgh et al. 2007 & Norden et al. 2008) or 350 mg/m<sup>2</sup> (Chen et al. 2007) IV over 90 minutes once on day 1, '''given first'''
 +
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1, '''given second, 90 minutes after the start of irinotecan'''
 
**Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later  
 
**Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later  
  
−
'''14-day cycles, given until progression of disease or unacceptable toxicity'''; Friedman et al. 2009 described 6-week cycles in which treatment was every 2 weeks, given up to 104 weeks, and was otherwise identical, so its entry was consolidated with the other ones here
+
====Supportive medications====
 +
*[[Steroid conversions|Steroids]] were generally maintained at the same dose
  
−
Supportive medications:
+
'''14-day cycles, given until progression of disease or unacceptable toxicity'''
−
*[[Steroid conversions|Steroids]] were generally maintained at the same dose
 
  
−
===Regimen #2, Vredenburgh et al. 2007 {{#subobject:7da12|Variant=1}}===
+
===Regimen #2 {{#subobject:7da12|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
−
style="background:#EEEE00;
+
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/25/30/4722.long Vredenburgh et al. 2007]
 +
|<span  
 +
style="background:#ff0000;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
 
border-color:black;
 
border-color:black;
 
border-width:2px;
 
border-width:2px;
−
border-style:solid;">Phase II</span>
+
border-style:solid;">Phase II, <20 pts</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 22, 29, '''given first'''
 +
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 350 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 22, 29, '''given first'''
 +
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once per day on days 1 & 22, '''given second, 90 minutes after the start of irinotecan'''
 +
**Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later
  
−
*[[Irinotecan (Camptosar)]] 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 22, 29, given first, before bevacizumab
+
====Supportive medications====
−
**Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: [[Irinotecan (Camptosar)]] 350 mg/m2 IV over 90 minutes once per day on days 1, 8, 22, 29, given first, before bevacizumab
+
*[[Steroid conversions|Steroids]] were generally maintained at the same dose  
−
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once per day on days 1 & 22, given second, 90 minutes after the start of irinotecan
 
−
**Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later
 
  
 
'''42-day (6-week) cycles, given until progression of disease or unacceptable toxicity'''
 
'''42-day (6-week) cycles, given until progression of disease or unacceptable toxicity'''
−
 
−
Supportive medications:
 
−
*[[Steroid conversions|Steroids]] were generally maintained at the same dose
 
  
 
===References===
 
===References===
Line 882: Line 1,139:
 
# 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. [http://jco.ascopubs.org/content/25/30/4722.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17947719 PubMed]
 
# 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. [http://jco.ascopubs.org/content/25/30/4722.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17947719 PubMed]
 
# Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008 Mar 4;70(10):779-87. [http://www.neurology.org/content/70/10/779.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18316689 PubMed]
 
# Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008 Mar 4;70(10):779-87. [http://www.neurology.org/content/70/10/779.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18316689 PubMed]
 +
<!-- Presented in part at the 12th Annual Meeting of the Society for Neuro-Oncology, November 15-18, 2007, Dallas, TX, and at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
 
# Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4733.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720927 PubMed]
 
# Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. [http://jco.ascopubs.org/content/27/28/4733.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19720927 PubMed]
  
Line 890: Line 1,148:
 
|}
 
|}
 
===Regimen {{#subobject:fc297c|Variant=1}}===
 
===Regimen {{#subobject:fc297c|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.neurology.org/content/63/7/1281.long Brandes et al. 2004]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 897: Line 1,159:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Carmustine (BiCNU)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
  
−
*[[Carmustine (BiCNU)]] 80 mg/m2 IV once per day on days 1 to 3
+
====Supportive medications====
−
 
 
−
'''8-week cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
 
*[[Antiemesis]] prophylaxis with [[Ondansetron (Zofran)]]  
 
*[[Antiemesis]] prophylaxis with [[Ondansetron (Zofran)]]  
 
*[[Steroid conversions|Steroids]] at lowest dose necessary
 
*[[Steroid conversions|Steroids]] at lowest dose necessary
 +
 +
'''8-week cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 915: Line 1,179:
 
|}
 
|}
 
===Regimen {{#subobject:d0ffd5|Variant=1}}===
 
===Regimen {{#subobject:d0ffd5|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.20072/full Chamberlain & Tsao-Wei, 2004]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 922: Line 1,190:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2
  
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m2 IV over 30 minutes once per day on days 1 & 2
+
====Supportive medications====
−
 
 
−
'''28-day cycles'''
 
−
 
 
−
Supportive medications:
 
 
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms
 
*[[Dexamethasone (Decadron)]] allowed for control of neurologic symptoms
−
*Ondansetron (Zofran) 0.15 mg/kg IV once prior to cyclophosphamide
+
*[[Ondansetron (Zofran)]] 0.15 mg/kg IV once prior to cyclophosphamide
 
*[[Dexamethasone (Decadron)]] 4 mg IV once prior to cyclophosphamide
 
*[[Dexamethasone (Decadron)]] 4 mg IV once prior to cyclophosphamide
 
*1 liter normal saline IV over 2 hours prior to cyclophosphamide
 
*1 liter normal saline IV over 2 hours prior to cyclophosphamide
−
*Prochlorperazine (Compazine) (dose/schedule not specified) prn nausea/vomiting
+
*[[Prochlorperazine (Compazine)]] (dose/schedule not specified) prn nausea/vomiting
 +
 
 +
'''28-day cycles'''
  
 
===References===
 
===References===
Line 943: Line 1,213:
 
|}
 
|}
  
−
===Regimen, Dresemann et al. 2005 {{#subobject:1c1791|Variant=1}}===
+
===Regimen {{#subobject:1c1791|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://annonc.oxfordjournals.org/content/16/10/1702.long Dresemann et al. 2005]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 951: Line 1,225:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
−
 
+
|-
−
''Dresemann et al. 2005 was a patient series.''
+
|}
 +
====Chemotherapy====
 
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 
*[[Hydroxyurea (Hydrea)]] 500 mg PO BID
 
*[[Hydroxyurea (Hydrea)]] 500 mg PO BID
  
−
'''given until progression of disease'''
+
'''Given until progression of disease'''
  
 
===References===
 
===References===
Line 967: Line 1,242:
 
|}
 
|}
 
===Regimen {{#subobject:24c9e2|Variant=1}}===
 
===Regimen {{#subobject:24c9e2|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/17/5/1516.long Friedman et al. 1999]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 974: Line 1,253:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
**If tolerated, dose could be increased to 150 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
  
−
*[[Irinotecan (Camptosar)]] 125 mg/m2 IV once per day on days 1, 8, 15, 22
+
====Supportive medications====
−
**If tolerated, dose could be increased to [[Irinotecan (Camptosar)]] 150 mg/m2 IV once per day on days 1, 8, 15, 22
+
*[[Steroid conversions|Steroids]] at lowest dose necessary
 +
*Avoid laxatives and magnesium-containing antacids due to potential for diarrhea
  
 
'''42-day (6-week) cycles, given until progression of disease or unacceptable toxicity'''
 
'''42-day (6-week) cycles, given until progression of disease or unacceptable toxicity'''
−
 
−
Supportive medications:
 
−
*[[Steroid conversions|Steroids]] at lowest dose necessary
 
−
*Avoid laxatives and magnesium-containing antacids due to potential for diarrhea
 
  
 
===References===
 
===References===
Line 1,008: Line 1,289:
 
|-
 
|-
 
|}
 
|}
 +
====Chemotherapy====
 +
*[[Lomustine (Ceenu)]] 100 to 130 mg/m<sup>2</sup> PO once on day 1
  
−
*[[Lomustine (Ceenu)]] 100 to 130 mg/m2 PO once on day 1
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*Enzyme-inducing antiepileptic drugs (EIAEDs) needed to be discontinued 14 days before enrolling in the trial
 
*Enzyme-inducing antiepileptic drugs (EIAEDs) needed to be discontinued 14 days before enrolling in the trial
  
Line 1,019: Line 1,300:
 
# Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, Mason W, Weller M, Hong S, Musib L, Liepa AM, Thornton DE, Fine HA. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010 Mar 1;28(7):1168-74. Epub 2010 Feb 1. [http://jco.ascopubs.org/content/28/7/1168.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20124186 PubMed]
 
# Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, Mason W, Weller M, Hong S, Musib L, Liepa AM, Thornton DE, Fine HA. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010 Mar 1;28(7):1168-74. Epub 2010 Feb 1. [http://jco.ascopubs.org/content/28/7/1168.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20124186 PubMed]
  
−
==PCV {{#subobject:2409e1|Regimen=1}}==
+
==PCV==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU, '''<u>V</u>'''incristine
+
PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''incristine
 +
 
 +
===Regimen #1 {{#subobject:c3f4c2|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.ncbi.nlm.nih.gov/pubmed/7407756 Levin et al. 1980]
 +
|<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21
 +
*[[Lomustine (Ceenu)]] 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
 +
 
 +
'''6-week cycles, given until progression of disease or unacceptable toxicity'''
 +
 
 +
===Regimen #2, higher doses {{#subobject:aba32b|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/12/10/2013.long Cairncross et al. 1994]
 +
|<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Procarbazine (Matulane)]] 75 mg/m<sup>2</sup> PO once per day on days 8 to 21
 +
*[[Lomustine (Ceenu)]] 130 mg/m<sup>2</sup> PO once on day 1
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (dose not capped) IV once per day on days 8 & 29
 +
 
 +
'''6-week cycles, given until progression of disease or unacceptable toxicity'''
  
−
*Regimens are the same as [[#PCV|PCV in Anaplastic glioma - recurrent disease, salvage therapy, Regimen #1, Levin et al. 1980 and Regimen #2, Cairncross et al. 1994]]
+
===References===
 +
# Levin VA, Edwards MS, Wright DC, Seager ML, Schimberg TP, Townsend JJ, Wilson CB. Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):237-44. '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7407756 PubMed]
 +
# Cairncross G, Macdonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr et al. Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1994 Oct;12(10):2013-21. [http://jco.ascopubs.org/content/12/10/2013.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/7931469 PubMed]
  
 
==Procarbazine (Matulane) {{#subobject:69a372|Regimen=1}}==
 
==Procarbazine (Matulane) {{#subobject:69a372|Regimen=1}}==
Line 1,034: Line 1,359:
 
|}
 
|}
 
===Regimen {{#subobject:d1a052|Variant=1}}===
 
===Regimen {{#subobject:d1a052|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.nature.com/bjc/journal/v83/n5/full/6691316a.html Yung et al. 2000]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,041: Line 1,370:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
  
−
*Patients who had never previously received chemotherapy: [[Procarbazine (Matulane)]] 150 mg/m2 PO once per day on days 1 to 28
+
====Chemotherapy====
−
*Patients who previously received chemotherapy started with [[Procarbazine (Matulane)]] 125 mg/m2 PO once per day on days 1 to 28
+
*[[Procarbazine (Matulane)]] as follows:
 +
**Patients who had never previously received chemotherapy: 150 mg/m<sup>2</sup> PO once per day on days 1 to 28
 +
**Patients who previously received chemotherapy started with 125 mg/m<sup>2</sup> PO once per day on days 1 to 28
  
−
'''8-week cycles x up to 2 years, progression of disease, or unacceptable toxicity'''
+
====Supportive medications====
 +
*[[Steroid conversions|Steroids]] at lowest dose necessary
  
−
Supportive medications:
+
'''8-week cycle for up to 2 years, progression of disease, or unacceptable toxicity'''
−
*[[Steroid conversions|Steroids]] at lowest dose necessary
 
  
 
===References===
 
===References===
Line 1,058: Line 1,391:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen #1, Perry et al. 2008 & Perry et al. 2010 - continuous therapy; RESCUE study {{#subobject:f18af9|Variant=1}}===
+
===Regimen #1, continuous therapy {{#subobject:f18af9|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full Perry et al. 2008 (RESCUE)]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,066: Line 1,403:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
 
+
|-
 +
|}
 +
====Chemotherapy====
 
Patients who have first recurrence after surgery and conventional external beam radiation:
 
Patients who have first recurrence after surgery and conventional external beam radiation:
−
*[[Temozolomide (Temodar)]] 150 to 200 mg/m2 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'''
  
 
Patients with progressive disease are changed to:
 
Patients with progressive disease are changed to:
−
*[[Temozolomide (Temodar)]] 50 mg/m2 PO once per day, taken continuously without treatment break
+
*[[Temozolomide (Temodar)]] 50 mg/m<sup>2</sup> PO once per day, taken continuously without treatment break
  
−
'''given until progression of disease or unacceptable toxicity'''
+
'''Given until progression of disease or unacceptable toxicity'''
  
 
Patients who had recurrent/progressive disease after surgery and concurrent radiation and temozolomide are treated with:
 
Patients who had recurrent/progressive disease after surgery and concurrent radiation and temozolomide are treated with:
−
*[[Temozolomide (Temodar)]] 50 mg/m2 PO once per day, taken continuously without treatment break
+
*[[Temozolomide (Temodar)]] 50 mg/m<sup>2</sup> PO once per day, taken continuously without treatment break
  
−
'''given until progression of disease or unacceptable toxicity'''
+
'''Given until progression of disease or unacceptable toxicity'''
 +
 
 +
===Regimen #2, traditional dosing {{#subobject:f06af9|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full Nicholson et al. 2007]
 +
|<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
**Patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
===Regimen #2, Nicholson et al. 2007 - traditional dosing {{#subobject:abc93e|Variant=1}}===
+
'''28-day cycle for up to 11 cycles'''
−
*Regimen is the same as [[#Temozolomide_.28Temodar.29_5|Temozolomide (Temodar) in supratentorial astrocytoma or oligodendroglioma recurrent disease, Regimen #4, Nicholson et al. 2007 - traditional dosing]]
 
  
−
===Regimen #3, Yung et al. 2000 {{#subobject:4cde86|Variant=1}}===
+
===Regimen #3 {{#subobject:4cde86|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.nature.com/bjc/journal/v83/n5/full/6691316a.html Yung et al. 2000]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,093: Line 1,453:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
  
−
*Patients who had never previously received chemotherapy: [[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
====Chemotherapy====
−
*Patients who previously received chemotherapy started with [[Temozolomide (Temodar)]] 150 mg/m2 PO once per day on days 1 to 5
+
*[[Temozolomide (Temodar)]] as follows:
 +
**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 started with 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
'''28-day cycles x up to 2 years, until progression of disease, or unacceptable toxicity'''
+
'''28-day cycle for up to 2 years, until progression of disease, or unacceptable toxicity'''
  
 
===References===
 
===References===
 
# Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000 Sep;83(5):588-93. [http://www.nature.com/bjc/journal/v83/n5/full/6691316a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10944597 PubMed]
 
# Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000 Sep;83(5):588-93. [http://www.nature.com/bjc/journal/v83/n5/full/6691316a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10944597 PubMed]
 +
# Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17705175 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18756530 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18756530 PubMed]
−
# 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. [http://jco.ascopubs.org/content/28/12/2051.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/28/12/2051.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20308655 PubMed]
  
 
=Supratentorial astrocytoma or oligodendroglioma chemoradiation & adjuvant therapy=
 
=Supratentorial astrocytoma or oligodendroglioma chemoradiation & adjuvant therapy=
Line 1,111: Line 1,476:
 
|}
 
|}
 
===Regimen {{#subobject:2344c2|Variant=1}}===
 
===Regimen {{#subobject:2344c2|Variant=1}}===
−
''Note: The patients in the reference were treated for glioblastoma, but the NCCN, Central Nervous System Cancers version 1.2013 lists this as an acceptable regimen for supratentorial astrocytoma or oligodendroglioma. No primary reference could be found for this regimen in this disease.''
+
''Note: The patients in the reference were treated for glioblastoma, but the NCCN, Central Nervous System Cancers version 1.2013 lists this as an acceptable regimen for supratentorial astrocytoma or oligodendroglioma. No primary reference could be found for this regimen in this disease.''
 +
====Chemoradiotherapy====
 
*Concurrent radiation therapy, 2 Gy fractions x 30 fractions given 5 days per week, for a total dose of 60 Gy
 
*Concurrent radiation therapy, 2 Gy fractions x 30 fractions given 5 days per week, for a total dose of 60 Gy
−
*[[Temozolomide (Temodar)]] 75 mg/m2 PO once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days
+
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days
  
 
4 weeks after completion of radiation therapy, patients received additional adjuvant therapy:
 
4 weeks after completion of radiation therapy, patients received additional adjuvant therapy:
−
*[[Temozolomide (Temodar)]] 150 mg/m2 PO once per day on days 1 to 5 of cycle 1; if tolerated, in cycles 2 and on, the dose is increased to [[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5 of cycle 1; if tolerated, in cycles 2 and on, the dose is increased to [[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
'''28-day cycles x 6 cycles'''
+
====Supportive medications====
−
 
 
−
Supportive medications:
 
 
*PCP prophylaxis during radiation therapy & temozolomide with one of the following:
 
*PCP prophylaxis during radiation therapy & temozolomide with one of the following:
 
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
 
**[[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
−
**Pentamidine (Nebupent) 300 mg nebulized inhaled
+
**[[Pentamidine (Nebupent)]] 300 mg nebulized inhaled
−
*Metoclopramide (Reglan) or [[Antiemesis|5-HT3 antagonist]] required during the adjuvant temozolomide-only period; their use was also recommended before the initial doses of radiation therapy & temozolomide
+
*[[Metoclopramide (Reglan)]] or [[Antiemesis|5-HT3 antagonist]] required during the adjuvant temozolomide-only period; their use was also recommended before the initial doses of radiation therapy & temozolomide
 +
 
 +
'''28-day cycle for 6 cycles'''
  
 
===References===
 
===References===
Line 1,136: Line 1,502:
 
|}
 
|}
 
===Regimen {{#subobject:24c607|Variant=1}}===
 
===Regimen {{#subobject:24c607|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://thejns.org/doi/pdf/10.3171/foc.1998.4.4.6 Moghrabi et al. 1998]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,143: Line 1,513:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
−
 
+
|-
−
*[[Carboplatin (Paraplatin)]] 560 mg/m2 IV over 1 hour once on day 1
+
|}
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] 560 mg/m<sup>2</sup> IV over 1 hour once on day 1
 
**Mixed in D5 1/2 NS
 
**Mixed in D5 1/2 NS
  
−
'''28-day cycles x up to 12 cycles beyond the maximum response, given until progression of disease, or unacceptable toxicity'''
+
====Supportive medications====
 +
*Hydration for 1 hour before chemotherapy, and for 1 hour after chemotherapy; total volume including carboplatin is 900 mL/m<sup>2</sup>
  
−
Supportive medications:
+
'''28-day cycle for up to 12 cycles beyond the maximum response, given until progression of disease, or unacceptable toxicity'''
−
*Hydration for 1 hour before chemotherapy, and for 1 hour after chemotherapy; total volume including carboplatin is 900 mL/m2
 
  
 
===References===
 
===References===
Line 1,161: Line 1,533:
 
|}
 
|}
 
===Regimen {{#subobject:531596|Variant=1}}===
 
===Regimen {{#subobject:531596|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://annonc.oxfordjournals.org/content/14/12/1727.long Brandes et al. 2003]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,168: Line 1,544:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] 350 mg/m<sup>2</sup> IV once on day 1
 +
*[[Teniposide (Vumon)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
  
−
*[[Carboplatin (Paraplatin)]] 350 mg/m2 IV once on day 1
+
====Supportive medications====
−
*[[Teniposide (Vumon)]] 50 mg/m2 IV once per day on days 1 to 3
 
−
 
 
−
'''28-day cycles x up to 10 cycles'''
 
−
 
 
−
Supportive medications:
 
 
*Prophylactic [[antiemesis|5-HT3 antagonists]] routinely used
 
*Prophylactic [[antiemesis|5-HT3 antagonists]] routinely used
 
*Lowest dose of [[Steroid conversions|corticosteroids]] necessary to maintain neurologic stability
 
*Lowest dose of [[Steroid conversions|corticosteroids]] necessary to maintain neurologic stability
 
*Antiepileptic medications for all patients
 
*Antiepileptic medications for all patients
 +
 +
'''28-day cycle for up to 10 cycles'''
  
 
===References===
 
===References===
Line 1,188: Line 1,566:
 
|}
 
|}
 
===Regimen {{#subobject:55de5f|Variant=1}}===
 
===Regimen {{#subobject:55de5f|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.springerlink.com/content/c34647v88t66m727/ Massimino et al. 2010]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,195: Line 1,577:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
''Note: In children <1 year old or <10 kg, "doses were adjusted to their weight"--reference does not say exactly how doses are adjusted.''
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 3, '''given first'''
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3, '''given second'''
  
−
*[[Cisplatin (Platinol)]] 25 mg/m2 IV over 2 hours once per day on days 1 to 3, given first
+
====Supportive medications====
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV over 30 minutes once per day on days 1 to 3, given second
+
*Hydration for 2 hours before chemotherapy, and for 2 hours after chemotherapy
−
*In children <1 year old or <10 kg, "doses were adjusted to their weight"--reference does not say exactly how doses are adjusted
 
−
 
 
−
'''28-day cycles x 4 cycles, then 35-day cycles x 3 cycles, then 42-day cycles x 3 cycles'''
 
  
−
Supportive medications:
+
'''28-day cycle for 4 cycles, then 35-day cycle for 3 cycles, then 42-day cycle for 3 cycles'''
−
*Hydration for 2 hours before chemotherapy, and for 2 hours after chemotherapy
 
  
 
===References===
 
===References===
Line 1,213: Line 1,597:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU, '''<u>V</u>'''incristine
+
PCV: '''<u>P</u>'''rocarbazine, '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''incristine
  
−
===Regimen, Brandes et al. 2004 {{#subobject:6c3103|Variant=1}}===
+
===Regimen {{#subobject:6c3103|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.20611/full Brandes et al. 2004]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,223: Line 1,611:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Procarbazine (Matulane)]] 60 mg/m<sup>2</sup> PO once per day on days 8 to 21
 +
*[[Lomustine (Ceenu)]] 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
  
−
*[[Procarbazine (Matulane)]] 60 mg/m2 PO once per day on days 8 to 21
+
====Supportive medications====
−
*[[Lomustine (Ceenu)]] 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
 
−
 
 
−
'''6-week cycles x up to 6 cycles'''
 
−
 
 
−
Supportive medications:
 
 
*Routine use of prophylactic [[antiemesis|5-HT3 antagonists]]
 
*Routine use of prophylactic [[antiemesis|5-HT3 antagonists]]
 
*[[Steroid conversions|Steroids]] given at the lowest dose required by patient's neurologic status
 
*[[Steroid conversions|Steroids]] given at the lowest dose required by patient's neurologic status
 +
 +
'''6-week cycle for up to 6 cycles'''
  
 
===References===
 
===References===
Line 1,243: Line 1,633:
 
|[[#toc|back to top]]
 
|[[#toc|back to top]]
 
|}
 
|}
−
===Regimen #1, Pouratian et al. 2007 - low dose {{#subobject:863ec|Variant=1}}===
+
===Regimen #1, low dose {{#subobject:863ec|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://www.springerlink.com/content/2015983316050j22/ Pouratian et al. 2006]
 +
|<span  
 
style="background:#ff0000;
 
style="background:#ff0000;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,251: Line 1,645:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Retrospective</span>
 
border-style:solid;">Retrospective</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 21
  
−
*[[Temozolomide (Temodar)]] 75 mg/m2 PO once per day on days 1 to 21
+
====Supportive medications====
−
 
 
−
'''28-day cycles x 12 to 15 cycles'''
 
−
 
 
−
Supportive medications:
 
 
*PCP prophylaxis with [[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
 
*PCP prophylaxis with [[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
 
*[[Antiemesis|Antiemetics]] and stool softeners used as needed
 
*[[Antiemesis|Antiemetics]] and stool softeners used as needed
  
−
===Regimen #2, Kesari et al. 2009 - low dose, longer cycles {{#subobject:50fd6b|Variant=1}}===
+
'''28-day cycle for 12 to 15 cycles'''
−
Level of Evidence:
+
 
−
<span  
+
===Regimen #2, low dose, longer cycles {{#subobject:50fd6b|Variant=1}}===
 +
{| border="1" style="text-align:center;" !align="left"
 +
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/15/1/330.long Kesari et al. 2009]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,268: Line 1,668:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase II</span>
 
border-style:solid;">Phase II</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 49
  
−
*[[Temozolomide (Temodar)]] 75 mg/m2 PO once per day on days 1 to 49
+
====Supportive medications====
 +
*PCP prophylaxis with [[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
  
−
'''77-day cycles x up to 6 cycles, progression of disease, or unacceptable toxicity'''
+
'''77-day cycle for up to 6 cycles, progression of disease, or unacceptable toxicity'''
  
−
Supportive medications:
+
===Regimen #3, traditional initial dosing, then continuous therapy {{#subobject:3871fe|Variant=1}}===
−
*PCP prophylaxis with [[Trimethoprim/Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim)]]
+
{| border="1" style="text-align:center;" !align="left"
−
 
+
|'''Study'''
−
===Regimen #3, Perry et al. 2008 - traditional initial dosing, then continuous therapy {{#subobject:3871fe|Variant=1}}===
+
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
−
Level of Evidence:
+
|-
−
<span  
+
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full Perry et al. 2008 (RESCUE)]
−
style="background:#ff0000;
+
|<span  
 +
style="background:#eeee00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
 
border-color:black;
 
border-color:black;
 
border-width:2px;
 
border-width:2px;
−
border-style:solid;">Retrospective</span>
+
border-style:solid;">Phase II</span>
−
 
+
|-
−
At first recurrence/progression:
+
|}
−
*[[Temozolomide (Temodar)]] 150 to 200 mg/m2 PO once per day on days 1 to 5
+
''At first recurrence/progression:''
 +
====Chemotherapy====
 +
*[[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'''
  
−
Patients with progressive disease are changed to:
+
''Patients with progressive disease are changed to:''
−
*[[Temozolomide (Temodar)]] 50 mg/m2 PO once per day, taken continuously without treatment break
+
*[[Temozolomide (Temodar)]] 50 mg/m<sup>2</sup> PO once per day, taken continuously without treatment break
  
−
'''given until progression of disease or unacceptable toxicity'''
+
'''Given until progression of disease or unacceptable toxicity'''
  
−
===Regimen #4, Chinot et al. 2001 & Nicholson et al. 2007 - traditional dosing {{#subobject:4fe632|Variant=1}}===
+
===Regimen #4, traditional dosing {{#subobject:4fe632|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|-
 +
|[http://jco.ascopubs.org/content/19/9/2449.long Chinot et al. 2001]
 +
|<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
|-
 +
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full Nicholson et al. 2007]
 +
|<span  
 
style="background:#EEEE00;
 
style="background:#EEEE00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
Line 1,303: Line 1,723:
 
border-width:2px;
 
border-width:2px;
 
border-style:solid;">Non-randomized</span>
 
border-style:solid;">Non-randomized</span>
 +
|-
 +
|}
 +
====Chemotherapy====
 +
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
 +
**In Nicholson et al. 2007, patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m<sup>2</sup> PO once per day on days 1 to 5
  
−
*[[Temozolomide (Temodar)]] 200 mg/m2 PO once per day on days 1 to 5
+
'''28-day cycle for up to 24 months (in Chinot et al. 2001) or 11 cycles (in Nicholson et al. 2007)'''
−
**In Nicholson et al. 2007, patients who previously received craniospinal irradiation (CSI) instead received [[Temozolomide (Temodar)]] 180 mg/m2 PO once per day on days 1 to 5
 
−
 
 
−
'''28-day cycles x up to 24 months (in Chinot et al. 2001) or 11 cycles (in Nicholson et al. 2007)'''
 
  
 
===References===
 
===References===
Line 1,314: Line 1,736:
 
# Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17705175 PubMed]
 
# Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22961/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17705175 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18756530 PubMed]
 
# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.23813/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18756530 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. [http://jco.ascopubs.org/content/28/12/2051.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20308655 PubMed]
 
# Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, Muzikansky A, Santagata S, Ligon KL, Norden AD, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black PM, Wen PY. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res. 2009 Jan 1;15(1):330-7. [http://clincancerres.aacrjournals.org/content/15/1/330.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19118062 PubMed]
 
# Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, Muzikansky A, Santagata S, Ligon KL, Norden AD, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black PM, Wen PY. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res. 2009 Jan 1;15(1):330-7. [http://clincancerres.aacrjournals.org/content/15/1/330.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19118062 PubMed]
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[[Category:Chemotherapy regimens]]
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[[Category:Central nervous system (CNS) regimens]]

Revision as of 01:05, 30 August 2016

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18 regimens on this page
36 variants on this page


Anaplastic glioma - adjuvant therapy

PCV

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PCV: Procarbazine, CCNU, Vincristine

Regimen

Study Evidence Comparator
Wick et al. 2009 (NOA-04) Phase III Radiation therapy
Temozolomide

Chemotherapy

8-week cycle for 4 cycles

Patients with stable disease or better received 2 more cycles of PCV. At time of disease progression patients proceeded to receive radiation therapy.

References

  1. 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 contains verified protocol PubMed

Radiation therapy

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Regimen

Study Evidence Comparator
MRC Brain Tumor Working Party 2001 Phase III RT -> PCV
van den Bent et al. 2006 (EORTC 26951) Phase III RT -> PCV
Wick et al. 2009 (NOA-04) Phase III PCV
Temozolomide

Adjuvant radiation alone; used as a comparator arm in the referenced trials.

Radiotherapy

  • Radiation therapy with 1.8 to 2 Gy fractions given over 6 weeks for a total dose of 60 Gy

Patients on the NOA-04 trial were randomized to PCV versus temozolomide at the time of progression.

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed
    1. 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
  3. 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 contains verified protocol PubMed

Radiation & Carmustine (BiCNU)

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Regimen

Study Evidence Comparator
Shapiro et al. 1989 (BTCG 8001) Phase III Carmustine/Procarbazine & RT
Carmustine & Hydrea/Procarbazine & VM-26 & RT

Radiotherapy

  • Radiation therapy starting within 3 weeks after surgical resection, with one of the following:
    • Whole brain: 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
    • Whole brain & cone down: 172 cGy (rads) fractions x 25 fractions, given over 5 weeks for a total dose of 4300 cGy (4300 rads), then coned-down boost of 172 cGy (rads) fractions x 10 fractions, given over 2 weeks for a dose of 1720 cGy (rads), and a total cumulative dose of 6020 cGy (rads)

One course, followed by:

Chemotherapy

8-week cycles, with no more than a maximum total dose of 1500 mg/m2 Carmustine (BiCNU) given

Supportive care:

  • Pulmonary function tests (PFTs) checked before start of therapy, and then when cumulative dose of Carmustine (BiCNU) reaches 800 mg/m2 and 1200 mg/m2

References

  1. Shapiro WR, Green SB, Burger PC, Mahaley MS Jr, Selker RG, VanGilder JC, Robertson JT, Ransohoff J, Mealey J Jr, Strike TA et al. Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg. 1989 Jul;71(1):1-9. link to original article contains verified protocol PubMed

RT -> PCV

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RT -> PCV: Radiation Therapy followed by Procarbazine, CCNU (Lomustine), Vincristine

Regimen #1

Study Evidence Comparator
MRC Brain Tumor Working Party 2001 Phase III Radiation therapy

Radiation therapy starts preferably within 3, but no more than 6, weeks after neurosurgery:

Radiotherapy

  • Either:
    • 2.25 Gy fractions x 20 fractions, given 5 days per week over 4 weeks, total dose of 45 Gy
    • or 2 Gy fractions x 30 fractions, given 5 days per week over 6 weeks, total dose of 60 Gy

Chemotherapy begins 3 to 4 weeks after completion of radiation therapy:

Chemotherapy

Supportive medications

  • 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.

6-week cycle for up to 12 cycles

Regimen #2

Study Evidence Comparator
van den Bent et al. 2006 (EORTC 26951) Phase III Radiation therapy

van den Bent et al. 2013 noted that 1p/19q-codeleted tumors received the more benefit from adjuvant PCV as compared to tumors without 1p/19q codeletion.

Radiation therapy starts within 6 weeks after surgery.

Radiotherapy

  • Radiation therapy, 1.8 Gy fractions x 25 fractions, given 5 days per week, total dose of 45 Gy to the planning target volume (PTV-1); then a boost of 1.8 Gy fractions x 8 fractions, given 5 days per week, total boost dose of 14.4 Gy to the PTV-2, for a total cumulative dose of 59.4 Gy

Chemotherapy begins within 4 weeks after completion of radiation therapy:

Chemotherapy

Supportive medications

6-week cycle for 6 cycles

References

  1. 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. PubMed
  2. 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 contains verified protocol PubMed
  3. 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 contains verified protocol PubMed
    1. 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

Temozolomide (Temodar)

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Regimen #1

Study Evidence Comparator
Wick et al. 2009 (NOA-04) Phase III PCV
Radiation therapy

Chemotherapy

28-day cycle for 8 cycles

Patients with stable disease or better received 4 more cycles of temozolomide. At time of disease progression patients proceeded to receive radiation therapy.

Regimen #2

Study Evidence
Mikkelsen et al. 2009 Non-randomized

This regimen is meant for patients with 1p/19q loss of heterozygosity (LOH).

Chemotherapy

  • Temozolomide (Temodar) as follows:
    • Cycles 1 & 2: 150 mg/m2 PO once per day on days 1 to 5, on empty stomach
    • Cycle 3 onwards (if no myelosuppression): 200 mg/m2 PO once per day on days 1 to 5, on empty stomach

28-day cycles

Regimen #3

Study Evidence
Taliansky-Aronov et al. 2006 Non-randomized

Chemotherapy

Supportive medications

  • Corticosteroids could be continued at same dose or reduced, but not increased while on study

28-day cycles, given until progression of disease or, in patients with stable disease, up to 24 months

References

  1. 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 contains verified protocol PubMed
  2. 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 contains verified protocol PubMed content property of HemOnc.org
  3. 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 contains verified protocol PubMed

Temozolomide -> Temozolomide & RT -> Temozolomide

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Regimen

Study Evidence
Mikkelsen et al. 2009 Non-randomized

This regimen is meant for patients without 1p/19q loss of heterozygosity (LOH).

Chemotherapy

  • Temozolomide (Temodar) as follows:
    • Cycles 1 & 2: 150 mg/m2 PO once per day on days 1 to 5, on empty stomach
    • Cycle 3 onwards (if no myelosuppression): 200 mg/m2 PO once per day on days 1 to 5, on empty stomach

28-day cycle for 2 to 4 cycles, followed by:

Chemoradiotherapy

  • Temozolomide (Temodar) 75 mg/m2 PO once per day during radiation therapy
  • Concurrent radiation therapy with a total dose of 60 Gy

One course, followed by:

Chemotherapy

28-day cycles

References

  1. 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 contains verified protocol PubMed content property of HemOnc.org

Anaplastic glioma - recurrent disease, salvage therapy

Bevacizumab (Avastin)

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Regimen

Study Evidence
Chamberlain et al. 2008 Non-randomized

Chemotherapy

Supportive medications

  • Use of steroids allowed for control of neurologic signs and symptoms

14-day cycles

References

  1. 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 contains verified protocol PubMed
  2. 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

Bevacizumab & Carboplatin

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Regimen #1

Study Evidence
Thompson et al. 2010 Retrospective

Chemotherapy

28-day cycles

Regimen #2

Study Evidence
Norden et al. 2008 Retrospective

Chemotherapy

References

  1. 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
  2. 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 PubMed

Bevacizumab & Irinotecan

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Regimen

Study Evidence
Vredenburgh et al. 2007 Phase II

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
    • Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 340 mg/m2 IV over 90 minutes once on day 1, given first
  • Bevacizumab (Avastin) 10 mg/kg IV once on day 1, given second
    • Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later

Supportive medications

  • "Appropriate antiemetics"

14-day cycles

References

  1. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Dowell JM, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Wagner M, Bigner DD, Friedman AH, Friedman HS. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007 Feb 15;13(4):1253-9. link to original article contains verified protocol PubMed
  2. 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

Cyclophosphamide (Cytoxan)

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Regimen

Study Evidence
Chamberlain et al. 2006 Phase II

Chemotherapy

Supportive medications

28-day cycles

References

  1. 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 contains verified protocol PubMed

Etoposide (Vepesid)

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Regimen

Study Evidence
Fulton et al. 1996 Phase II

Chemotherapy

Given until progression of disease or unacceptable toxicity

References

  1. 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 contains verified protocol PubMed

Irinotecan (Camptosar)

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Regimen #1

Study Evidence
Chamberlain et al. 2008 Phase II

Chemotherapy

  • Irinotecan (Camptosar) 350 mg/m2 IV over 120 minutes once on day 1
    • Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 600 mg/m2 IV over 120 minutes once on day 1

Supportive medications

21-day cycles

Regimen #2

Study Evidence
Friedman et al. 1999 Phase II

Chemotherapy

  • Irinotecan (Camptosar) 125 mg/m2 IV once per day on days 1, 8, 15, 22
    • If tolerated, dose could be increased to 150 mg/m2 IV once per day on days 1, 8, 15, 22

Supportive medications

  • Steroids at lowest dose necessary
  • Avoid laxatives and magnesium-containing antacids due to potential for diarrhea

42-day (6-week) cycles, given until progression of disease or unacceptable toxicity

References

  1. Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL. Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol. 1999 May;17(5):1516-25. link to original article contains verified protocol PubMed
  2. Phase I: Chamberlain MC. Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas. J Neurooncol. 2002 Sep;59(2):157-63. link to original article PubMed
  3. 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 contains verified protocol PubMed

Lomustine (Ceenu)

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  • Note: The NCCN, Central Nervous System Cancers version 1.2013 lists this regimen (Wick et al. 2010) with Lomustine (Ceenu) salvage therapy in glioblastoma multiforme as an option for treatment of anaplastic gliomas. This study only included patients who had histologically confirmed WHO grade 4 glioblastoma. The NCCN also listed the following phase II trial as a reference for use of Carmustine (BiCNU)/Lomustine (Ceenu) in recurrent malignant glioma, but the nitrosourea used was fotemustine (FTM): R. Soffietti, R. Rudà, E. Trevisan, E. Picco, D. Guarneri, M. Caroli, M. Fabrini, V. Scotti. Phase II study of bevacizumab and nitrosourea in patients with recurrent malignant glioma: A multicenter Italian study. CNS Tumors 2012 J Clin Oncol 27:15s, 2009 (suppl; abstr 2012). 2009 ASCO Annual Meeting abstract 2012. link to abstract

PCV

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PCV: Procarbazine, CCNU (Lomustine), Vincristine

Regimen #1

Study Evidence Comparator
Wick et al. 2009 (NOA-04) Phase III Temozolomide

All patients had progressed after previously receiving radiation therapy, salvage temozolomide, or salvage radiation therapy.

Chemotherapy

8-week cycles until progression

At progression, patients who had not previously received temozolomide proceeded to receive salvage temozolomide.

Regimen #2

Study Evidence
Levin et al. 1980 Non-randomized

Chemotherapy

6-week cycles, given until progression of disease or unacceptable toxicity

Regimen #3, higher doses

Study Evidence
Cairncross et al. 1994 Phase II

Chemotherapy

6-week cycles, given until progression of disease or unacceptable toxicity

References

  1. Levin VA, Edwards MS, Wright DC, Seager ML, Schimberg TP, Townsend JJ, Wilson CB. Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):237-44. contains protocol PubMed
  2. Cairncross G, Macdonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr et al. Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1994 Oct;12(10):2013-21. link to original article contains verified protocol PubMed
  3. 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
  4. 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 contains verified protocol PubMed

Radiation therapy

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Regimen

Study Evidence Comparator
Wick et al. 2009 (NOA-04) Phase III PCV
Temozolomide

Patients had previously received PCV versus temozolomide prior to progression.

Radiotherapy

  • Radiation therapy with 1.8 to 2 Gy fractions given over 6 weeks for a total dose of 60 Gy

Patients who progressed then received PCV if they had previously received temozolomide, or temozolomide if they had previously received PCV.

References

  1. 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 contains verified protocol PubMed

Temozolomide (Temodar)

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Regimen #1

Study Evidence Comparator
Wick et al. 2009 (NOA-04) Phase III PCV

All patients had progressed after previously receiving radiation therapy, salvage PCV, or salvage radiation therapy.

Chemotherapy

28-day cycles until progression

At progression, patients who had not previously received PCV proceeded to receive salvage PCV.

Regimen #2, continuous therapy

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

Patients who undergo conventional temozolomide therapy, have surgery and radiation therapy, and then relapse receive:

Chemotherapy

28-day cycles

Patients with progressive disease are changed to:

Given until progression of disease or unacceptable toxicity

Regimen #3, traditional dosing

Study Evidence
Nicholson et al. 2007 Non-randomized

Chemotherapy

  • Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
    • Patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m2 PO once per day on days 1 to 5

28-day cycle for up to 11 cycles

Regimen #4

Study Evidence
Yung et al. 1999 Phase II

Chemotherapy

  • Temozolomide (Temodar) as follows:
    • Patients who had never previously received chemotherapy: 200 mg/m2 PO once per day on days 1 to 5
    • Patients who previously received chemotherapy started with 150 mg/m2 PO once per day on days 1 to 5, which could be increased as tolerated to 200 mg/m2 PO once per day on days 1 to 5

Supportive medications

28-day cycle for up to 2 years

References

  1. 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. Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group. J Clin Oncol. 1999 Sep;17(9):2762-71. link to original article contains verified protocol PubMed
  2. Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. link to original article contains verified protocol PubMed
  3. Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the "rescue" approach. Cancer. 2008 Oct 15;113(8):2152-7. link to original article contains verified protocol PubMed
    1. Update: Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, Shields C, Kirby S, Macdonald DR, Eisenstat DD, Thiessen B, Forsyth P, Pouliot JF. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20;28(12):2051-7. Epub 2010 Mar 22. link to original article contains verified protocol PubMed
  4. 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 contains verified protocol PubMed

Glioblastoma multiforme chemoradiation & adjuvant therapy

Radiation

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Regimen

Study Evidence Comparator
Stupp et al. 2005 Phase III Radiation & Temozolomide -> Temozolomide

Adjuvant radiation alone; used as a comparator arm in the referenced trials.

References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. link to original article contains verified protocol PubMed

Radiation & Carmustine (BiCNU)

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Regimen

Study Evidence Comparator
Shapiro et al. 1989 (BTCG 8001) Phase III Carmustine/Procarbazine & RT
Carmustine & Hydrea/Procarbazine & VM-26 & RT

Radiotherapy

  • Radiation therapy starting within 3 weeks after surgical resection, with one of the following:
    • Whole brain: 172 cGy (rads) fractions x 35 fractions, given over 7 weeks for a total dose of 6020 cGy (6020 rads/~1700 rets)
    • Whole brain & cone down: 172 cGy (rads) fractions x 25 fractions, given over 5 weeks for a total dose of 4300 cGy (4300 rads), then coned-down boost of 172 cGy (rads) fractions x 10 fractions, given over 2 weeks for a dose of 1720 cGy (rads), and a total cumulative dose of 6020 cGy (rads)

One course, followed by:

Chemotherapy

8-week cycles, with no more than a maximum total dose of 1500 mg/m2 Carmustine (BiCNU) given

Supportive care:

  • Pulmonary function tests (PFTs) checked before start of therapy, and then when cumulative dose of Carmustine (BiCNU) reaches 800 mg/m2 and 1200 mg/m2

References

  1. Shapiro WR, Green SB, Burger PC, Mahaley MS Jr, Selker RG, VanGilder JC, Robertson JT, Ransohoff J, Mealey J Jr, Strike TA et al. Randomized trial of three chemotherapy regimens and two radiotherapy regimens and two radiotherapy regimens in postoperative treatment of malignant glioma. Brain Tumor Cooperative Group Trial 8001. J Neurosurg. 1989 Jul;71(1):1-9. link to original article contains verified protocol PubMed

Radiation & Temozolomide -> Temozolomide

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Regimen

Study Evidence Comparator
Stupp et al. 2005 Phase III Radiation
Gilbert et al. 2014 Phase III Bevacizumab, Temozolomide, RT
Chinot et al. 2014 Phase III Bevacizumab, Temozolomide, RT

Chemoradiotherapy

  • Temozolomide (Temodar) 75 mg/m2 PO once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days
  • Concurrent radiation therapy, 2 Gy fractions x 30 fractions given 5 days per week, for a total dose of 60 Gy

Supportive medications

One course

4 weeks after completion of radiation therapy, patients received additional therapy:

Chemotherapy

  • Temozolomide (Temodar) as follows:
    • Cycle 1: 150 mg/m2 PO once per day on days 1 to 5
    • If tolerated, in cycles 2 to 6: 200 mg/m2 PO once per day on days 1 to 5

Supportive medications

28-day cycle for 6 cycles

References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. link to original article contains verified protocol PubMed
    1. Subgroup analysis: Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. link to original article PubMed
  2. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. link to original article PubMed
  3. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. link to original article PubMed

Glioblastoma multiforme - recurrent disease, salvage therapy

Bevacizumab (Avastin)

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Regimen #1

Study Evidence Comparator
Friedman et al. 2009 Randomized Phase II Bevacizumab & Irinotecan

Chemotherapy

6-week cycle for up to 104 weeks, until progression of disease, or unacceptable toxicity

Regimen #2

Study Evidence
Kreisl et al. 2008 Phase II

Chemotherapy

4-week cycles, given until progression of disease, or unacceptable toxicity; upon progression, patients received Irinotecan (Camptosar) & Bevacizumab (Avastin)

References

  1. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA. Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol. 2009 Feb 10;27(5):740-5. Epub 2008 Dec 29. link to original article contains verified protocol PubMed
  2. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. link to original article contains verified protocol PubMed

Bevacizumab & Carboplatin

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Regimen #1

Study Evidence
Thompson et al. 2010 Retrospective

Chemotherapy

28-day cycles

Regimen #2

Study Evidence
Norden et al. 2008 Retrospective

Chemotherapy

References

  1. 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
  2. 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 PubMed

Bevacizumab & Irinotecan

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Regimen #1, every 2 week schedule

Study Evidence Comparator
Chen et al. 2007 Pilot, >20 pts
Vredenburgh et al. 2007 Phase II
Norden et al. 2008 Phase II
Friedman et al. 2009 Randomized Phase II Bevacizumab

Note: Friedman et al. 2009 described 6-week cycles in which treatment was every 2 weeks, given up to 104 weeks, and was otherwise identical, so its entry was consolidated with the other ones here.

Chemotherapy

  • Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once on day 1, given first
    • Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 340 mg/m2 (Vredenburgh et al. 2007 & Norden et al. 2008) or 350 mg/m2 (Chen et al. 2007) IV over 90 minutes once on day 1, given first
  • Bevacizumab (Avastin) 10 mg/kg IV once on day 1, given second, 90 minutes after the start of irinotecan
    • Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later

Supportive medications

  • Steroids were generally maintained at the same dose

14-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study Evidence
Vredenburgh et al. 2007 Phase II, <20 pts

Chemotherapy

  • Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 22, 29, given first
    • Patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) are treated with a higher dose: 350 mg/m2 IV over 90 minutes once per day on days 1, 8, 22, 29, given first
  • Bevacizumab (Avastin) 15 mg/kg IV once per day on days 1 & 22, given second, 90 minutes after the start of irinotecan
    • Infusion times for bevacizumab are 90 minutes for the first dose, then if tolerated, 60 minutes for the second dose, and 30 minutes for the third dose and later

Supportive medications

  • Steroids were generally maintained at the same dose

42-day (6-week) cycles, given until progression of disease or unacceptable toxicity

References

  1. Chen W, Delaloye S, Silverman DH, Geist C, Czernin J, Sayre J, Satyamurthy N, Pope W, Lai A, Phelps ME, Cloughesy T. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J Clin Oncol. 2007 Oct 20;25(30):4714-21. link to original article contains verified protocol PubMed
  2. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007 Oct 20;25(30):4722-9. link to original article contains verified protocol PubMed
  3. Norden AD, Young GS, Setayesh K, Muzikansky A, Klufas R, Ross GL, Ciampa AS, Ebbeling LG, Levy B, Drappatz J, Kesari S, Wen PY. Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008 Mar 4;70(10):779-87. link to original article contains verified protocol PubMed
  4. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. Epub 2009 Aug 31. link to original article contains verified protocol PubMed

Carmustine (BiCNU)

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Regimen

Study Evidence
Brandes et al. 2004 Phase II

Chemotherapy

Supportive medications

8-week cycle for up to 6 cycles

References

  1. Brandes AA, Tosoni A, Amistà P, Nicolardi L, Grosso D, Berti F, Ermani M. How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial. Neurology. 2004 Oct 12;63(7):1281-4. link to original article contains verified protocol PubMed

Cyclophosphamide (Cytoxan)

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Regimen

Study Evidence
Chamberlain & Tsao-Wei, 2004 Phase II

Chemotherapy

Supportive medications

28-day cycles

References

  1. Chamberlain MC, Tsao-Wei DD. Salvage chemotherapy with cyclophosphamide for recurrent, temozolomide-refractory glioblastoma multiforme. Cancer. 2004 Mar 15;100(6):1213-20. link to original article contains verified protocol PubMed

Hydroxyurea & Imatinib

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Regimen

Study Evidence
Dresemann et al. 2005 Non-randomized

Chemotherapy

Given until progression of disease

References

  1. Dresemann G. Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme: a patient series. Ann Oncol. 2005 Oct;16(10):1702-8. Epub 2005 Jul 20. link to original article contains verified protocol PubMed

Irinotecan (Camptosar)

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Regimen

Study Evidence
Friedman et al. 1999 Phase II

Chemotherapy

  • Irinotecan (Camptosar) 125 mg/m2 IV once per day on days 1, 8, 15, 22
    • If tolerated, dose could be increased to 150 mg/m2 IV once per day on days 1, 8, 15, 22

Supportive medications

  • Steroids at lowest dose necessary
  • Avoid laxatives and magnesium-containing antacids due to potential for diarrhea

42-day (6-week) cycles, given until progression of disease or unacceptable toxicity

References

  1. Friedman HS, Petros WP, Friedman AH, Schaaf LJ, Kerby T, Lawyer J, Parry M, Houghton PJ, Lovell S, Rasheed K, Cloughsey T, Stewart ES, Colvin OM, Provenzale JM, McLendon RE, Bigner DD, Cokgor I, Haglund M, Rich J, Ashley D, Malczyn J, Elfring GL, Miller LL. Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol. 1999 May;17(5):1516-25. link to original article contains verified protocol PubMed

Lomustine (Ceenu)

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Regimen

Study Evidence Comparator
Wick et al. 2010 Phase III Enzastaurin

Chemotherapy

Supportive medications

  • Enzyme-inducing antiepileptic drugs (EIAEDs) needed to be discontinued 14 days before enrolling in the trial

6-week cycles, given until progression of disease or unacceptable toxicity

References

  1. Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, Mason W, Weller M, Hong S, Musib L, Liepa AM, Thornton DE, Fine HA. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010 Mar 1;28(7):1168-74. Epub 2010 Feb 1. link to original article contains verified protocol PubMed

PCV

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PCV: Procarbazine, CCNU (Lomustine), Vincristine

Regimen #1

Study Evidence
Levin et al. 1980 Non-randomized

Chemotherapy

6-week cycles, given until progression of disease or unacceptable toxicity

Regimen #2, higher doses

Study Evidence
Cairncross et al. 1994 Phase II

Chemotherapy

6-week cycles, given until progression of disease or unacceptable toxicity

References

  1. Levin VA, Edwards MS, Wright DC, Seager ML, Schimberg TP, Townsend JJ, Wilson CB. Modified procarbazine, CCNU, and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep. 1980 Feb-Mar;64(2-3):237-44. contains protocol PubMed
  2. Cairncross G, Macdonald D, Ludwin S, Lee D, Cascino T, Buckner J, Fulton D, Dropcho E, Stewart D, Schold C Jr et al. Chemotherapy for anaplastic oligodendroglioma. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1994 Oct;12(10):2013-21. link to original article contains verified protocol PubMed

Procarbazine (Matulane)

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Regimen

Study Evidence
Yung et al. 2000 Phase II

Chemotherapy

  • Procarbazine (Matulane) as follows:
    • Patients who had never previously received chemotherapy: 150 mg/m2 PO once per day on days 1 to 28
    • Patients who previously received chemotherapy started with 125 mg/m2 PO once per day on days 1 to 28

Supportive medications

8-week cycle for up to 2 years, progression of disease, or unacceptable toxicity

References

  1. Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000 Sep;83(5):588-93. link to original article contains verified protocol PubMed

Temozolomide (Temodar)

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Regimen #1, continuous therapy

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

Chemotherapy

Patients who have first recurrence after surgery and conventional external beam radiation:

28-day cycles

Patients with progressive disease are changed to:

Given until progression of disease or unacceptable toxicity

Patients who had recurrent/progressive disease after surgery and concurrent radiation and temozolomide are treated with:

Given until progression of disease or unacceptable toxicity

Regimen #2, traditional dosing

Study Evidence
Nicholson et al. 2007 Non-randomized

Chemotherapy

  • Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
    • Patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m2 PO once per day on days 1 to 5

28-day cycle for up to 11 cycles

Regimen #3

Study Evidence
Yung et al. 2000 Phase II

Chemotherapy

  • Temozolomide (Temodar) as follows:
    • Patients who had never previously received chemotherapy: 200 mg/m2 PO once per day on days 1 to 5
    • Patients who previously received chemotherapy started with 150 mg/m2 PO once per day on days 1 to 5

28-day cycle for up to 2 years, until progression of disease, or unacceptable toxicity

References

  1. Yung WK, Albright RE, Olson J, Fredericks R, Fink K, Prados MD, Brada M, Spence A, Hohl RJ, Shapiro W, Glantz M, Greenberg H, Selker RG, Vick NA, Rampling R, Friedman H, Phillips P, Bruner J, Yue N, Osoba D, Zaknoen S, Levin VA. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000 Sep;83(5):588-93. link to original article contains verified protocol PubMed
  2. Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. link to original article contains verified protocol PubMed
  3. Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the "rescue" approach. Cancer. 2008 Oct 15;113(8):2152-7. link to original article contains verified protocol PubMed
    1. Update: Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, Shields C, Kirby S, Macdonald DR, Eisenstat DD, Thiessen B, Forsyth P, Pouliot JF. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20;28(12):2051-7. Epub 2010 Mar 22. link to original article contains verified protocol PubMed

Supratentorial astrocytoma or oligodendroglioma chemoradiation & adjuvant therapy

Temozolomide (Temodar)

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Regimen

Note: The patients in the reference were treated for glioblastoma, but the NCCN, Central Nervous System Cancers version 1.2013 lists this as an acceptable regimen for supratentorial astrocytoma or oligodendroglioma. No primary reference could be found for this regimen in this disease.

Chemoradiotherapy

  • Concurrent radiation therapy, 2 Gy fractions x 30 fractions given 5 days per week, for a total dose of 60 Gy
  • Temozolomide (Temodar) 75 mg/m2 PO once per day, used starting the first day of radiation therapy until the last day of radiation therapy, and no longer than 49 days

4 weeks after completion of radiation therapy, patients received additional adjuvant therapy:

Supportive medications

28-day cycle for 6 cycles

References

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. link to original article contains verified protocol PubMed

Supratentorial astrocytoma or oligodendroglioma - recurrent or progressive, low-grade disease

Carboplatin (Paraplatin)

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Regimen

Study Evidence
Moghrabi et al. 1998 Phase II

Chemotherapy

Supportive medications

  • Hydration for 1 hour before chemotherapy, and for 1 hour after chemotherapy; total volume including carboplatin is 900 mL/m2

28-day cycle for up to 12 cycles beyond the maximum response, given until progression of disease, or unacceptable toxicity

References

  1. Moghrabi A, Friedman HS, Ashley DM, Bottom KS, Kerby T, Stewart E, Bruggers C, Provenzale JM, Champagne M, Hershon L, Watral M, Ryan J, Rasheed K, Lovell S, Korones D, Fuchs H, George T, McLendon RE, Friedman AH, Buckley E, Longee DC. Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas. Neurosurg Focus. 1998 Apr 15;4(4):e3. link to original article contains verified protocol PubMed

Carboplatin & Teniposide

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Regimen

Study Evidence
Brandes et al. 2003 Phase II

Chemotherapy

Supportive medications

  • Prophylactic 5-HT3 antagonists routinely used
  • Lowest dose of corticosteroids necessary to maintain neurologic stability
  • Antiepileptic medications for all patients

28-day cycle for up to 10 cycles

References

  1. Brandes AA, Basso U, Vastola F, Tosoni A, Pasetto LM, Jirillo A, Lonardi S, Paris MK, Koussis H, Monfardini S, Ermani M. Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study. Ann Oncol. 2003 Dec;14(12):1727-31. link to original article contains verified protocol PubMed

Cisplatin & Etoposide

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Regimen

Study Evidence
Massimino et al. 2010 Non-randomized

Note: In children <1 year old or <10 kg, "doses were adjusted to their weight"--reference does not say exactly how doses are adjusted.

Chemotherapy

Supportive medications

  • Hydration for 2 hours before chemotherapy, and for 2 hours after chemotherapy

28-day cycle for 4 cycles, then 35-day cycle for 3 cycles, then 42-day cycle for 3 cycles

References

  1. Massimino M, Spreafico F, Riva D, Biassoni V, Poggi G, Solero C, Gandola L, Genitori L, Modena P, Simonetti F, Potepan P, Casanova M, Meazza C, Clerici CA, Catania S, Sardi I, Giangaspero F. A lower-dose, lower-toxicity cisplatin-etoposide regimen for childhood progressive low-grade glioma. J Neurooncol. 2010 Oct;100(1):65-71. Epub 2010 Feb 12. link to original article contains verified protocol PubMed

PCV

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PCV: Procarbazine, CCNU (Lomustine), Vincristine

Regimen

Study Evidence
Brandes et al. 2004 Phase II

Chemotherapy

Supportive medications

6-week cycle for up to 6 cycles

References

  1. Brandes AA, Tosoni A, Vastola F, Pasetto LM, Coria B, Danieli D, Iuzzolino P, Gardiman M, Talacchi A, Ermani M. Efficacy and feasibility of standard procarbazine, lomustine, and vincristine chemotherapy in anaplastic oligodendroglioma and oligoastrocytoma recurrent after radiotherapy. A Phase II study. Cancer. 2004 Nov 1;101(9):2079-85. link to original article contains verified protocol PubMed
  2. Triebels VH, Taphoorn MJ, Brandes AA, Menten J, Frenay M, Tosoni A, Kros JM, Stege EB, Enting RH, Allgeier A, van Heuvel I, van den Bent MJ. Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas. Neurology. 2004 Sep 14;63(5):904-6. link to original article PubMed

Temozolomide (Temodar)

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Regimen #1, low dose

Study Evidence
Pouratian et al. 2006 Retrospective

Chemotherapy

Supportive medications

28-day cycle for 12 to 15 cycles

Regimen #2, low dose, longer cycles

Study Evidence
Kesari et al. 2009 Phase II

Chemotherapy

Supportive medications

77-day cycle for up to 6 cycles, progression of disease, or unacceptable toxicity

Regimen #3, traditional initial dosing, then continuous therapy

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

At first recurrence/progression:

Chemotherapy

28-day cycles

Patients with progressive disease are changed to:

Given until progression of disease or unacceptable toxicity

Regimen #4, traditional dosing

Study Evidence
Chinot et al. 2001 Phase II
Nicholson et al. 2007 Non-randomized

Chemotherapy

  • Temozolomide (Temodar) 200 mg/m2 PO once per day on days 1 to 5
    • In Nicholson et al. 2007, patients who previously received craniospinal irradiation (CSI) instead received 180 mg/m2 PO once per day on days 1 to 5

28-day cycle for up to 24 months (in Chinot et al. 2001) or 11 cycles (in Nicholson et al. 2007)

References

  1. Chinot OL, Honore S, Dufour H, Barrie M, Figarella-Branger D, Muracciole X, Braguer D, Martin PM, Grisoli F. Safety and efficacy of temozolomide in patients with recurrent anaplastic oligodendrogliomas after standard radiotherapy and chemotherapy. J Clin Oncol. 2001 May 1;19(9):2449-55. link to original article contains verified protocol PubMed
  2. Pouratian N, Gasco J, Sherman JH, Shaffrey ME, Schiff D. Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas. J Neurooncol. 2007 May;82(3):281-8. Epub 2006 Nov 3. link to original article contains verified protocol PubMed
  3. Nicholson HS, Kretschmar CS, Krailo M, Bernstein M, Kadota R, Fort D, Friedman H, Harris MB, Tedeschi-Blok N, Mazewski C, Sato J, Reaman GH. Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group. Cancer. 2007 Oct 1;110(7):1542-50. link to original article contains verified protocol PubMed
  4. Perry JR, Rizek P, Cashman R, Morrison M, Morrison T. Temozolomide rechallenge in recurrent malignant glioma by using a continuous temozolomide schedule: the "rescue" approach. Cancer. 2008 Oct 15;113(8):2152-7. link to original article contains verified protocol PubMed
    1. Update: Perry JR, Bélanger K, Mason WP, Fulton D, Kavan P, Easaw J, Shields C, Kirby S, Macdonald DR, Eisenstat DD, Thiessen B, Forsyth P, Pouliot JF. Phase II trial of continuous dose-intense temozolomide in recurrent malignant glioma: RESCUE study. J Clin Oncol. 2010 Apr 20;28(12):2051-7. Epub 2010 Mar 22. link to original article contains verified protocol PubMed
  5. Kesari S, Schiff D, Drappatz J, LaFrankie D, Doherty L, Macklin EA, Muzikansky A, Santagata S, Ligon KL, Norden AD, Ciampa A, Bradshaw J, Levy B, Radakovic G, Ramakrishna N, Black PM, Wen PY. Phase II study of protracted daily temozolomide for low-grade gliomas in adults. Clin Cancer Res. 2009 Jan 1;15(1):330-7. link to original article contains verified protocol PubMed
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