Difference between revisions of "Editing test page"

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==Thalidomide monotherapy {{#subobject:ff02e1|Regimen=1}}==
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<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
 
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[[#top|Back to Top]]
 
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</div>
 
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{{#lst:Section editor transclusions|aml}}
 
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<big>'''Note: these are regimens tested in biomarker-specific populations for patients with NPM1-mutated AML, please see the [[Acute myeloid leukemia|main AML page]] for other regimens.'''</big>
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
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=="How I Treat"==
 
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*'''2021:''' Falini et al. [https://doi.org/10.1182/blood.2020008211 How I diagnose and treat NPM1-mutated AML]
 
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=Upfront induction therapy=
 
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==Cytarabine & Etoposide {{#subobject:e8gacb|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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===Regimen {{#subobject:15hvdd|Variant=1}}===
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===Synopsis===
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{| class="wikitable sortable" style="width: 100%; text-align:center;"
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'''Historical Background of Thalidomide'''
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!style="width: 20%"|Study
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!style="width: 20%"|Dates of enrollment
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Originally developed and marketed in the late 1950s as a sedative and remedy for morning sickness in pregnant women, thalidomide led to catastrophic birth defects when taken during pregnancy. Due to these teratogenic effects, its usage was banned in many countries by the early 1960s.
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!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 20%"|Comparator
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'''Rediscovery and Anticancer Properties'''
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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
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|-
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During the late 1990s, the anti-angiogenic and immunomodulatory effects of thalidomide were explored. Researchers hypothesized that these properties could be harnessed against cancers that rely on angiogenesis.
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|[https://www.clinicaltrials.gov/study/NCT01237808 Awaiting publication (AMLSG 15-10)]
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|2011-NR
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Singhal et al., 1999 ([https://pubmed.ncbi.nlm.nih.gov/10564685/] Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. New England Journal of Medicine. 1999;341:1565-71): This seminal study reported the effects of thalidomide in patients with refractory multiple myeloma. Thalidomide showed significant antitumor activity, leading to renewed interest in the drug.
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| style="background-color:#1a9851" |Phase 3 (C)
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|[[Stub#ATRA.2C_Cytarabine.2C_Etoposide|ATRA, Cytarabine, Etoposide]]
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'''Development of Analogues'''
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| style="background-color:#d3d3d3" |Not available
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|-
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The success of thalidomide spurred the development of its analogues, designed to retain its therapeutic benefits while minimizing side effects. Lenalidomide and pomalidomide are two such analogues that have shown significant efficacy in multiple myeloma with a better side effect profile.
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|}
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<div class="toccolours" style="background-color:#b3e2cd">
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'''Current Role in Therapy'''
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====Chemotherapy====
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*[[Cytarabine (Ara-C)]]
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While newer agents and combinations have emerged in the treatment landscape of multiple myeloma, thalidomide and its derivatives remain vital components in various treatment regimens, especially in certain settings and geographies.
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*[[Etoposide (Vepesid)]]
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</div></div>
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'''Conclusion'''
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===References===
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#'''AMLSG 15-10:''' [https://clinicaltrials.gov/study/NCT01237808 NCT01237808]
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The repositioning of thalidomide for multiple myeloma is a testament to the importance of re-evaluating existing drugs for new therapeutic indications. Its successful transition from a notorious drug to a vital component in the multiple myeloma treatment arsenal underscores the ever-evolving nature of drug development and therapy.
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==ICE & ATRA {{#subobject:e82156|Regimen=1}}==
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<br><small>The background material for this synopsis was generated by Chat-GPT and then further edited by the page editor for accuracy and style. See this page for more information.</small>
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ICE & ATRA: '''<u>I</u>'''darubicin, '''<u>C</u>'''ytarabine, '''<u>E</u>'''toposide, '''<u>A</u>'''ll-'''<u>T</u>'''rans '''<u>R</u>'''etinoic '''<u>A</u>'''cid
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</div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
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===Regimen variant #1, 60 or younger {{#subobject:cf53dd|Variant=1}}===
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===Regimen {{#subobject:43a4e3|Variant=1}}===
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{| class="wikitable sortable" style="width: 100%; text-align:center;"  
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
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!style="width: 20%"|Study
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!style="width: 33%"|Study
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!style="width: 20%"|Dates of enrollment
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!style="width: 33%"|Dates of enrollment
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!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 20%"|Comparator
 
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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
 
|-
 
|-
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ Schlenk et al. 2019 (AMLSG 09-09)]
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|[https://doi.org/10.1056/NEJM199911183412102 Singhal et al. 1999]
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|2010-2017
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|1997-1998
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| style="background-color:#1a9851" |Phase 3 (C)
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|style="background-color:#91cf61"|Non-randomized
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|[[#ICE.2C_ATRA.2C_GO_999|ICE, ATRA, GO]]
 
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| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
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====Chemotherapy====
 
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*[[Idarubicin (Idamycin)]] as follows:
 
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**Cycle 1: 12 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
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**Cycle 2: 12 mg/m<sup>2</sup> IV once per day on days 1 & 3
 
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*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose per cycle: 700 mg/m<sup>2</sup>)
 
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*[[Etoposide (Vepesid)]] as follows:
 
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**Cycle 1: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
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**Cycle 2: 100 mg/m<sup>2</sup> IV once per day on days 1 & 3
 
 
====Targeted therapy====
 
====Targeted therapy====
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*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO on days 6 to 8, then 15 mg/m<sup>2</sup>/day PO on days 9 to 21
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*[[Thalidomide (Thalomid)]] 200 mg PO once per day, increased by 200 mg every two weeks for six weeks, to final dose of 800 mg per day
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'''2 cycles'''
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'''Continued indefinitely'''
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</div>
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</div></div>
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<div class="toccolours" style="background-color:#cbd5e7">
 
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====Subsequent treatment====
 
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*[[#HiDAC_.26_ATRA_888|HiDAC & ATRA]] consolidation
 
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</div></div><br>
 
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<div class="toccolours" style="background-color:#eeeeee">
 
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===Regimen variant #2, older than 60 {{#subobject:cfghcd|Variant=1}}===
 
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{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
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!style="width: 20%"|Study
 
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!style="width: 20%"|Dates of enrollment
 
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!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
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!style="width: 20%"|Comparator
 
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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
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|-
 
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ Schlenk et al. 2019 (AMLSG 09-09)]
 
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|2010-2017
 
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| style="background-color:#1a9851" |Phase 3 (C)
 
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|[[#ICE.2C_ATRA.2C_GO_999|ICE, ATRA, GO]]
 
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| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
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<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 1 & 3
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose per cycle: 700 mg/m<sup>2</sup>)
 
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*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 3
 
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====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO on days 6 to 8, then 15 mg/m<sup>2</sup>/day PO on days 9 to 21
 
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'''2 cycles'''
 
−
</div>
 
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<div class="toccolours" style="background-color:#cbd5e7">
 
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====Subsequent treatment====
 
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*[[#HiDAC_.26_ATRA_888|HiDAC & ATRA]] consolidation
 
−
</div>
 
 
===References===
 
===References===
−
# '''AMLSG 09-09:''' Schlenk RF, Paschka P, Krzykalla J, Weber D, Kapp-Schwoerer S, Gaidzik VI, Leis C, Fiedler W, Kindler T, Schroeder T, Mayer K, Lübbert M, Wattad M, Götze K, Horst HA, Koller E, Wulf G, Schleicher J, Bentz M, Greil R, Hertenstein B, Krauter J, Martens U, Nachbaur D, Abu Samra M, Girschikofsky M, Basara N, Benner A, Thol F, Heuser M, Ganser A, Döhner K, Döhner H. Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study. J Clin Oncol. 2020 Feb 20;38(6):623-632. Epub 2019 Dec 18. [https://doi.org/10.1200/JCO.19.01406 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030890/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31851556/ PubMed] [https://clinicaltrials.gov/study/XCT00893399 clinical trial link]
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# Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeldis J, Siegel D, Crowley J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. [https://doi.org/10.1056/NEJM199911183412102 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10564685/ PubMed]
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[[Category:Acute myeloid leukemia regimens]]
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# Yakoub-Agha I, Mary JY, Hulin C, Doyen C, Marit G, Benboubker L, Voillat L, Moreau P, Berthou C, Stoppa AM, Maloisel F, Rodon P, Dib M, Pegourie B, Casassus P, Slama B, Damaj G, Zerbib R, Harousseau JL, Mohty M, Facon T; Intergroupe Francophone du Myélome (IFM). Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome. Eur J Haematol. 2012 Mar;88(3):249-59. Epub 2012 Jan 4. [https://doi.org/10.1111/j.1600-0609.2011.01729.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/22023551/ PubMed]
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[[Category:Biomarker-specific pages]]
 
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[[Category:Acute leukemias]]
 

Revision as of 18:57, 10 August 2023

Thalidomide monotherapy

Synopsis

Historical Background of Thalidomide

Originally developed and marketed in the late 1950s as a sedative and remedy for morning sickness in pregnant women, thalidomide led to catastrophic birth defects when taken during pregnancy. Due to these teratogenic effects, its usage was banned in many countries by the early 1960s.

Rediscovery and Anticancer Properties

During the late 1990s, the anti-angiogenic and immunomodulatory effects of thalidomide were explored. Researchers hypothesized that these properties could be harnessed against cancers that rely on angiogenesis.

Singhal et al., 1999 ([1] Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. New England Journal of Medicine. 1999;341:1565-71): This seminal study reported the effects of thalidomide in patients with refractory multiple myeloma. Thalidomide showed significant antitumor activity, leading to renewed interest in the drug.

Development of Analogues

The success of thalidomide spurred the development of its analogues, designed to retain its therapeutic benefits while minimizing side effects. Lenalidomide and pomalidomide are two such analogues that have shown significant efficacy in multiple myeloma with a better side effect profile.

Current Role in Therapy

While newer agents and combinations have emerged in the treatment landscape of multiple myeloma, thalidomide and its derivatives remain vital components in various treatment regimens, especially in certain settings and geographies.

Conclusion

The repositioning of thalidomide for multiple myeloma is a testament to the importance of re-evaluating existing drugs for new therapeutic indications. Its successful transition from a notorious drug to a vital component in the multiple myeloma treatment arsenal underscores the ever-evolving nature of drug development and therapy.
The background material for this synopsis was generated by Chat-GPT and then further edited by the page editor for accuracy and style. See this page for more information.


Regimen

Study Dates of enrollment Evidence
Singhal et al. 1999 1997-1998 Non-randomized

Targeted therapy

  • Thalidomide (Thalomid) 200 mg PO once per day, increased by 200 mg every two weeks for six weeks, to final dose of 800 mg per day

Continued indefinitely

References

  1. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeldis J, Siegel D, Crowley J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. link to original article contains dosing details in abstract PubMed
  2. Yakoub-Agha I, Mary JY, Hulin C, Doyen C, Marit G, Benboubker L, Voillat L, Moreau P, Berthou C, Stoppa AM, Maloisel F, Rodon P, Dib M, Pegourie B, Casassus P, Slama B, Damaj G, Zerbib R, Harousseau JL, Mohty M, Facon T; Intergroupe Francophone du Myélome (IFM). Low-dose vs. high-dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome. Eur J Haematol. 2012 Mar;88(3):249-59. Epub 2012 Jan 4. link to original article PubMed
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