Difference between revisions of "Erdheim-Chester disease"

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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]].'''
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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]].'''  
  
−
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]].
  
 
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|<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>
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|<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>
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<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>
 
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|-
 
|-
 
|[http://www.bloodjournal.org/content/126/10/1163.long Gianfreda et al. 2015]
 
|[http://www.bloodjournal.org/content/126/10/1163.long Gianfreda et al. 2015]
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|<span
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|style="background-color:#ff0000"|Pilot, <20 pts in this arm
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style="background:#ff0000;
 
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border-style:solid;">Pilot, <20 patients in this arm</span>
 
 
|-
 
|-
 
|}
 
|}
−
 
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====Chemotherapy====
 
*[[Sirolimus (Rapamune)]] 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
 
*[[Sirolimus (Rapamune)]] 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
 
*[[Prednisone (Sterapred)]] as follows:
 
*[[Prednisone (Sterapred)]] as follows:
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|-
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 Hyman et al. 2015]
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 Hyman et al. 2015]
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|<span
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|style="background-color:#ff0000"|Phase II, <20 pts in this arm
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style="background:#ff0000;
 
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border-style:solid;">Phase II, <20 patients in this arm</span>
 
 
|-
 
|-
 
|}
 
|}
−
 
 
''This was part of a basket trial, all patients had BRAF V600E mutations.''
 
''This was part of a basket trial, all patients had BRAF V600E mutations.''
−
 
+
====Chemotherapy====
 
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
 
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
  
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|-
 
|-
 
|[http://jco.ascopubs.org/content/33/5/411.full Haroche et al. 2014]
 
|[http://jco.ascopubs.org/content/33/5/411.full Haroche et al. 2014]
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|<span
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|style="background-color:#ff0000"|Pilot, <20 pts
−
style="background:#ff0000;
 
−
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border-color:black;
 
−
border-width:2px;
 
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border-style:solid;">Pilot, <20 patients</span>
 
 
|-
 
|-
 
|}
 
|}
 
''Patients enrolled all had BRAF V600E mutation. This is the dose after de-escalation after the first four patients had excess adverse events.''
 
''Patients enrolled all had BRAF V600E mutation. This is the dose after de-escalation after the first four patients had excess adverse events.''
 +
====Chemotherapy====
 
*[[Vemurafenib (Zelboraf)]] 480 mg PO BID
 
*[[Vemurafenib (Zelboraf)]] 480 mg PO BID
  
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|-
 
|-
 
|}
 
|}
−
 
 
To be completed
 
To be completed
 +
====Chemotherapy====
 
*[[Cladribine (Leustatin)]]
 
*[[Cladribine (Leustatin)]]
  
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|-
 
|-
 
|}
 
|}
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====Chemotherapy, induction====
 
*[[Cladribine (Leustatin)]] 9 mg/m2 IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine'''
 
*[[Cladribine (Leustatin)]] 9 mg/m2 IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine'''
 
**Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
 
**Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
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''Patients with a "good response" proceeded to consolidation therapy:''
 
''Patients with a "good response" proceeded to consolidation therapy:''
  
 +
====Chemotherapy, consolidation====
 
*[[Cladribine (Leustatin)]] 5 mg/m2 IV once per day on days 1 to 3
 
*[[Cladribine (Leustatin)]] 5 mg/m2 IV once per day on days 1 to 3
  
−
'''21-day cycle x 2 cycles, followed by multidrug maintentance therapy:'''
+
'''21-day cycle x 2 cycles, followed by:'''
  
 +
====Chemotherapy, maintenance====
 
*[[Vinblastine (Velban)]] 6 mg/m2 IV once every 2 weeks x 6 months
 
*[[Vinblastine (Velban)]] 6 mg/m2 IV once every 2 weeks x 6 months
 
*[[Prednisolone (Millipred)]] 40 mg/m2 PO once per day on days 1 to 5 of every 2nd week x 6 months
 
*[[Prednisolone (Millipred)]] 40 mg/m2 PO once per day on days 1 to 5 of every 2nd week x 6 months
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|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|'''Comparator'''
 
|'''Comparator'''
 +
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
 
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
 
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 +
|style="background-color:#eeee00"|Seems not superior
 
|-
 
|-
 
|}
 
|}
−
 
 
To be completed
 
To be completed
 +
====Chemotherapy====
 
*[[Etoposide (Vepesid)]]
 
*[[Etoposide (Vepesid)]]
 
*[[Prednisone (Sterapred)]]
 
*[[Prednisone (Sterapred)]]
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|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|'''Comparator'''
 
|'''Comparator'''
 +
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2008 (LCH-II)]
+
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
 
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 +
|style="background-color:#eeee00"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 +
''Total duration of therapy is 24 weeks.''
 +
====Chemotherapy, initial====
 +
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once per week
 +
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
  
−
To be completed
+
'''6-week course, followed by:'''
−
*[[Etoposide (Vepesid)]]
+
 
−
*[[Vinblastine (Velban)]]
+
====Chemotherapy, continuation====
−
*[[Prednisone (Sterapred)]]
+
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 1 hour once on day 1
 +
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
 +
 
 +
'''3-week cycle for 6 cycles'''
  
 
===References===
 
===References===
−
# Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
+
# Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
  
 
==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}==
 
==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}==
Line 222: Line 222:
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|'''Comparator'''
 
|'''Comparator'''
 +
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
 
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 
|[[Histiocytoses#Vinblastine_.26_Prednisone|Vinblastine & Prednisone]]
 +
|style="background-color:#eeee00"|Seems not superior
 
|-
 
|-
 
|}
 
|}
−
 
 
To be completed
 
To be completed
 +
====Chemotherapy====
 
*[[Methotrexate (MTX)]]
 
*[[Methotrexate (MTX)]]
 
*[[Vinblastine (Velban)]]
 
*[[Vinblastine (Velban)]]
Line 249: Line 251:
 
|-
 
|-
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 Hyman et al. 2015]
 
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1502309 Hyman et al. 2015]
−
|<span
+
|style="background-color:#ff0000"|Phase II, <20 pts in this arm
−
style="background:#ff0000;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II, <20 patients in this arm</span>
 
 
|-
 
|-
 
|}
 
|}
−
 
 
''This was part of a basket trial, all patients had BRAF V600E mutations.''
 
''This was part of a basket trial, all patients had BRAF V600E mutations.''
−
 
+
====Chemotherapy====
 
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
 
*[[Vemurafenib (Zelboraf)]] 960 mg PO BID
  
Line 278: Line 274:
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 
|'''Comparator'''
 
|'''Comparator'''
 +
|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 
|-
 
|-
 
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 
|[http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract Gadner et al. 2001 (LCH-I)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
 
|[[Histiocytoses#Etoposide_.26_Prednisone|Etoposide & Prednisone]]
 
|[[Histiocytoses#Etoposide_.26_Prednisone|Etoposide & Prednisone]]
 +
|style="background-color:#eeee00"|Seems not superior
 
|-
 
|-
−
!colspan="4" align="center"|
+
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2007 (LCH-II)]
−
|-
 
−
|[http://www.bloodjournal.org/content/111/5/2556.long Gadner et al. 2008 (LCH-II)]
 
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
 
|[[Histiocytoses#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]]
 
|[[Histiocytoses#Etoposide.2C_Vinblastine.2C_Prednisone|Etoposide, Vinblastine, Prednisone]]
−
|-
+
|style="background-color:#eeee00"|Seems not superior
−
!colspan="4" align="center"|
 
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
|[http://www.bloodjournal.org/content/121/25/5006.long Gadner et al. 2013 (LCH-III)]
 
|style="background-color:#00CD00"|Phase III
 
|style="background-color:#00CD00"|Phase III
 
|[[Histiocytoses#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]]
 
|[[Histiocytoses#Methotrexate.2C_Vinblastine.2C_Prednisone|Methotrexate, Vinblastine, Prednisone]]
 +
|style="background-color:#eeee00"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 +
''Total duration of therapy is 24 weeks, in LCH-II.''
 +
====Chemotherapy, initial====
 +
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per week
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID for 4 weeks, then tapering off over 2 weeks
  
−
To be completed
+
'''6-week course, followed by:'''
−
*[[Vinblastine (Velban)]]
+
 
−
*[[Prednisone (Sterapred)]]
+
====Chemotherapy, continuation====
 +
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once on day 1
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day split TID on days 1 to 5
 +
 
 +
'''3-week cycle for 6 cycles'''
  
 
===References===
 
===References===
 
# Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
 
# Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [http://www.jpeds.com/article/S0022-3476(01)07325-5/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11343051 PubMed]
−
# Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
+
# Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [http://www.bloodjournal.org/content/111/5/2556.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18089850 PubMed]
 
# Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [http://www.bloodjournal.org/content/121/25/5006.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]
 
# Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [http://www.bloodjournal.org/content/121/25/5006.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23589673 PubMed]

Revision as of 02:02, 25 December 2016

Use of this site is subject to you reading and agreeing with the terms set forth in the 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 invited to contribute to the site.

3 regimens on this page
4 variants on this page


Erdheim-Chester disease (ECD)

Sirolimus & Prednisone

back to top

Regimen

Study Evidence
Gianfreda et al. 2015 Pilot, <20 pts in this arm

Chemotherapy

  • Sirolimus (Rapamune) 2 mg PO once per day, titrated to achieve a blood level of 8 to 12 ng/mL
  • Prednisone (Sterapred) as follows:
    • Month 1: 0.75 mg/kg/day PO
    • Month 2: 0.5 mg/k/day PO
    • Months 3 & 4: 0.25 mg/kg/day PO
    • Months 5 & 6: 0.125 mg/kg/day PO
    • Month 7 onwards: tapered to a dose of 2.5 to 5 mg PO once per day

Given for up to 2 years for responders and stable disease, with optional extension beyond 2 years

References

  1. Gianfreda D, Nicastro M, Galetti M, Alberici F, Corradi D, Becchi G, Baldari G, De Filippo M, Ferretti S, Moroni G, Foti R, Di Gangi M, Jeannin G, Saffroy R, Emile JF, Buzio C, Vaglio A. Sirolimus plus prednisone for Erdheim-Chester disease: an open-label trial. Blood. 2015 Sep 3;126(10):1163-71. Epub 2015 Jun 3. link to original article contains verified protocol PubMed

Vemurafenib (Zelboraf)

back to top

Regimen #1

Study Evidence
Hyman et al. 2015 Phase II, <20 pts in this arm

This was part of a basket trial, all patients had BRAF V600E mutations.

Chemotherapy

Duration of treatment not specified

Regimen #2

Study Evidence
Haroche et al. 2014 Pilot, <20 pts

Patients enrolled all had BRAF V600E mutation. This is the dose after de-escalation after the first four patients had excess adverse events.

Chemotherapy

Given until progression of disease or unacceptable toxicity

References

  1. Haroche J, Cohen-Aubart F, Emile JF, Maksud P, Drier A, Tolédano D, Barete S, Charlotte F, Cluzel P, Donadieu J, Benameur N, Grenier PA, Besnard S, Ory JP, Lifermann F, Idbaih A, Granel B, Graffin B, Hervier B, Arnaud L, Amoura Z. Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease. J Clin Oncol. 2015 Feb 10;33(5):411-8. Epub 2014 Nov 24. link to original article contains verified protocol PubMed
  2. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains protocol PubMed

Langerhans cell histiocytosis (LCH)

Cladribine (Leustatin)

back to top

Regimen

Study Evidence
Weitzman et al. 2009 (LCH-S-98) Phase II

To be completed

Chemotherapy

References

  1. Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH). results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. link to original article PubMed

Cladribine & Cytarabine

back to top

Regimen

Study Evidence
Donadieu et al. 2015 Phase II

Chemotherapy, induction

  • Cladribine (Leustatin) 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
    • Children weighing less than 10 kg received a dose of 0.3 mg/kg/day
  • Cytarabine (Cytosar) 500 mg/m2 IV over 2 hours twice per day on days 1 to 5, should not be administered simultaneously with cladribine

5-week cycle x 2 or more cycles

Patients with a "good response" proceeded to consolidation therapy:

Chemotherapy, consolidation

21-day cycle x 2 cycles, followed by:

Chemotherapy, maintenance

Total of 18 months of maintenance

References

  1. Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article contains verified protocol PubMed

Etoposide & Prednisone

back to top

Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2001 (LCH-I) Phase III Vinblastine & Prednisone Seems not superior

To be completed

Chemotherapy

References

  1. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed

Etoposide, Vinblastine, Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2007 (LCH-II) Phase III Vinblastine & Prednisone Seems not superior

Total duration of therapy is 24 weeks.

Chemotherapy, initial

6-week course, followed by:

Chemotherapy, continuation

3-week cycle for 6 cycles

References

  1. Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains verified protocol PubMed

Methotrexate, Vinblastine, Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2013 (LCH-III) Phase III Vinblastine & Prednisone Seems not superior

To be completed

Chemotherapy

References

  1. Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed

Vemurafenib (Zelboraf)

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Regimen

Study Evidence
Hyman et al. 2015 Phase II, <20 pts in this arm

This was part of a basket trial, all patients had BRAF V600E mutations.

Chemotherapy

Duration of treatment not specified

References

  1. Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in Multiple Nonmelanoma Cancers with BRAF V600 Mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains protocol PubMed

Vinblastine & Prednisone

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Regimen

Study Evidence Comparator Efficacy
Gadner et al. 2001 (LCH-I) Phase III Etoposide & Prednisone Seems not superior
Gadner et al. 2007 (LCH-II) Phase III Etoposide, Vinblastine, Prednisone Seems not superior
Gadner et al. 2013 (LCH-III) Phase III Methotrexate, Vinblastine, Prednisone Seems not superior

Total duration of therapy is 24 weeks, in LCH-II.

Chemotherapy, initial

6-week course, followed by:

Chemotherapy, continuation

3-week cycle for 6 cycles

References

  1. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed
  2. Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains verified protocol PubMed
  3. Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed
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