Difference between revisions of "Staging page"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
Line 3: Line 3:
 
[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
−
{{#lst:Section editor transclusions|inhl}}
+
{{#lst:Section editor transclusions|sarcoma}}
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
Line 9: Line 9:
 
<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>
 
<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>
 
|}
 
|}
−
<big>'''Note: these are regimens specific to extranodal marginal zone lymphomas (EMZL) of mucosa-associated lymphoid tissue ("MALTomas"), please see the [[Marginal zone lymphoma|main MZL page]] for other regimens.'''</big>
+
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Soft_tissue_sarcoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Soft tissue sarcoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.
 +
<br>Note: this page is for subtype-nonspecific soft tissue sarcoma regimens, some subtypes with very few subtype-specific regimens, as well as for sarcomas that are not readily categorized, e.g., alveolar soft part sarcoma. Please see the [[:Category:Soft tissue sarcomas|category page]] for links to other sarcoma types or use one of these links:
 +
*[[Desmoid tumors]]
 +
*[[Epithelioid sarcoma]]
 +
*[[Gastrointestinal stromal tumor|Gastrointestinal stromal tumor (GIST)]]
 +
*[[Leiomyosarcoma]]
 +
*[[Liposarcoma]]
 +
*[[PEComa]]
 +
*[[Rhabdomyosarcoma]]
 +
*[[Tenosynovial giant cell tumor|Tenosynovial giant cell tumor (TGCT)]]
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
−
==EGILS==
+
==ESMO/EURACAN/GENTURIS==
−
*'''2011:''' Ruskoné-Fourmestraux et al. [http://dx.doi.org/10.1136/gut.2010.224949 EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT]
+
*'''2021:''' Gronchi et al. [https://doi.org/10.1016/j.annonc.2021.07.006 Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up]
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2020:''' Zucca et al. [https://doi.org/10.1016/j.annonc.2019.10.010 Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
 
===Older===
 
===Older===
−
*'''2013:''' Dreyling et al. [https://doi.org/10.1093/annonc/mds643 ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma] [https://pubmed.ncbi.nlm.nih.gov/23425945 PubMed]
+
*'''2018:''' Casali et al. [https://www.esmo.org/Guidelines/Sarcoma-and-GIST/Soft-Tissue-and-Visceral-Sarcomas Soft tissue and visceral sarcomas: ESMO–EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up]
−
*'''2013:''' Zucca et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Gastric-Marginal-Zone-Lymphoma-of-MALT-Type Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+
*'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/25210080 PubMed]
−
===Older===
 
−
*'''2009:''' Zucca et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdp146 Gastric marginal zone lymphoma of MALT type: ESMO Clinical Recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454427 PubMed]
 
 
==[https://www.nccn.org/ NCCN]==
 
==[https://www.nccn.org/ NCCN]==
−
*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
+
*[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma]
−
=Gastric MALT lymphoma, H. Pylori eradication therapy=
+
*[https://www.nccn.org/professionals/physician_gls/pdf/dfsp.pdf NCCN Guidelines - Dermatofibrosarcoma Protuberans (DFSP)]
−
==Amoxicillin & PPI {{#subobject:69pnz5|Regimen=1}}==
+
=Neoadjuvant therapy=
 +
==Epirubicin & Ifosfamide {{#subobject:eeb76b|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:6a2ui9|Variant=1}}===
+
===Regimen {{#subobject:aea2c8|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2011.37.7218 Gronchi et al. 2012]
 +
|2002-2007
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(95)90113-2 Bayerdörffer et al. 1995]
+
|[https://doi.org/10.1016/S1470-2045(17)30334-0 Gronchi et al. 2017 (ISG-STS 1001)]
−
| style="background-color:#91cf61" |Non-randomized
+
|2011-2016
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|Histotype-tailored therapy
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy for ISG-STS 1001 is based on the 2020 update.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibiotic therapy====
+
====Chemotherapy====
−
*[[Amoxicillin]] 750 mg PO three times per day
+
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2
−
*[[Omeprazole (Prilosec)]] 40 mg PO three times per day
+
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 to 3
−
'''14-day course'''
+
====Supportive therapy====
 +
*[[Mesna (Mesnex)]] 1000 mg/m<sup>2</sup> IV every 3 hours to every 4 hours on days 1 to 3
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Gronchi et al. 2012: [[Surgery#Surgical_resection|Surgery]], then adjuvant [[#Epirubicin_.26_Ifosfamide|EI]] x 2 versus [[#Observation|no further treatment]]
 +
*ISG-STS 1001: [[Surgery#Surgical_resection|Surgery]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Bayerdörffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M; MALT Lymphoma Study Group. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet. 1995 Jun 24;345(8965):1591-4. [https://doi.org/10.1016/S0140-6736(95)90113-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7783535 PubMed]
+
# Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, Mariani L, Valagussa P, Miceli R, Stacchiotti S, Dei Tos AP, De Paoli A, Longhi A, Poveda A, Quagliuolo V, Comandone A, Casali PG, Picci P; Italian Sarcoma Group; Spanish Sarcoma Group. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012 Mar 10;30(8):850-6. Epub 2012 Feb 6. [https://doi.org/10.1200/JCO.2011.37.7218 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22312103 PubMed] EudraCT 2004-003979-36
−
## '''Update:''' Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wündisch T, Ehninger G, Stolte M, Bayerdörffer E. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst. 1997 Sep 17;89(18):1350-5. [https://doi.org/10.1093/jnci/89.18.1350 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9308704 PubMed]
+
# '''ISG-STS 1001:''' Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. [https://doi.org/10.1016/S1470-2045(17)30334-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28499583 PubMed] NCT01710176
−
## '''Update:''' Wündisch T, Thiede C, Morgner A, Dempfle A, Günther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdörffer E, Stolte M, Neubauer A. Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol. 2005 Nov 1;23(31):8018-24. Epub 2005 Oct 3. [https://doi.org/10.1200/jco.2005.02.3903 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16204012 PubMed]
+
##'''Update:''' Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez Pousa A, Grignani G, Brunello A, Blay JY, Tendero O, Diaz Beveridge R, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Braglia L, Donati DM, Palassini E, Bianchi G, Marrari A, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. J Clin Oncol. 2020 Jul 1;38(19):2178-2186. Epub 2020 May 18. [https://doi.org/10.1200/jco.19.03289 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32421444 PubMed]
−
==Amoxicillin, Clarithromycin, PPI, Bismuth {{#subobject:0hgba5|Regimen=1}}==
+
==EIA {{#subobject:0608ad|Regimen=1}}==
 +
EIA: '''<u>E</u>'''toposide, '''<u>I</u>'''fosfamide, '''<u>A</u>'''driamycin (Doxorubicin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:6iqsn1|Variant=1}}===
+
===Regimen {{#subobject:52e303|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.7326/0003-4819-131-2-199907200-00003 Steinbach et al. 1999]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ Issels et al. 2010 (EORTC 62961/ESHO 95)]
−
| style="background-color:#91cf61" |Non-randomized
+
|1997-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#EIA_.26_regional_hyperthemia_88|EIA & regional hyperthermia]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibiotic therapy====
+
====Chemotherapy====
−
*[[Amoxicillin]] 750 mg PO three times per day on days 1 to 21
+
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 1 & 4
−
*[[Clarithromycin (Biaxin)]] 500 mg PO three times per day on days 1 to 21
+
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 4
−
*[[Omeprazole (Prilosec)]] or [[Lansoprazole (Prevacid)]]
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
*[[Bismuth subsalicylate (Pepto-Bismol)]]
+
'''21-day cycle for 4 cycles'''
−
'''8-week cycle for 2 cycles'''
+
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Surgery]], then [[Regimen_classes#Radiotherapy|RT]], then adjuvant [[#EIA_2|EIA]] x 4
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
#Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. [https://doi.org/10.7326/0003-4819-131-2-199907200-00003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10419446 PubMed]
+
# '''EORTC 62961/ESHO 95:''' Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. Epub 2010 Apr 29. [https://doi.org/10.1016/S1470-2045(10)70071-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20434400 PubMed] NCT00003052
−
==Ampicillin, Metronidazole, Bismuth {{#subobject:be3ef5|Regimen=1}}==
+
## '''Update:''' Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):483-492. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2672386 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29450452 PubMed]
 +
=Adjuvant therapy=
 +
==EIA {{#subobject:8d8ff1|Regimen=1}}==
 +
EIA: '''<u>E</u>'''toposide, '''<u>I</u>'''fosfamide, '''<u>A</u>'''driamycin (Doxorubicin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:6a2469|Variant=1}}===
+
===Regimen {{#subobject:6d8a81|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1016/0140-6736(93)91409-F Wotherspoon et al. 1993]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ Issels et al. 2010 (EORTC 62961/ESHO 95)]
−
| style="background-color:#ffffbe" |Pilot
+
|1997-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#EIA_.26_regional_hyperthemia_88|EIA & regional hyperthermia]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Neoadjuvant [[#EIA|EIA]] x 4, then [[Surgery#Surgical_resection|surgery]], then adjuvant RT
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibiotic therapy====
+
====Chemotherapy====
−
*[[Ampicillin]]
+
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 1 & 4
−
*[[Metronidazole (Flagyl)]]
+
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 4
−
*[[Tripotassium dicitratobismuthate (De-Noltab)]]
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 4 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):575-7. [https://doi.org/10.1016/0140-6736(93)91409-F link to original article] [https://pubmed.ncbi.nlm.nih.gov/8102719 PubMed]
+
# '''EORTC 62961/ESHO 95:''' Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. Epub 2010 Apr 29. [https://doi.org/10.1016/S1470-2045(10)70071-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3517819/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20434400 PubMed] NCT00003052
−
==Ampicillin & PPI {{#subobject:be2nz5|Regimen=1}}==
+
## '''Update:''' Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):483-492. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2672386 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885262/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29450452 PubMed]
 +
=Locally advanced or metastatic disease, single-agent regimens=
 +
==Cisplatin monotherapy {{#subobject:6e93fa|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:6a2ui9|Variant=1}}===
+
===Regimen {{#subobject:2ff0fe|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1016/0140-6736(93)91409-F Wotherspoon et al. 1993]
+
|[https://doi.org/10.1016/S1470-2045(15)70102-6 Blay et al. 2015 (EFC10145)]
−
| style="background-color:#ffffbe" |Pilot
+
|2008-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Ombrabulin_77|Cisplatin & Ombrabulin]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
|-
 
|-
 
|}
 
|}
 +
''Note: PFS was very poor in both groups (less than 2 months); the difference was not considered clinically meaningful.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibiotic therapy====
+
====Chemotherapy====
−
*[[Ampicillin]]
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
−
*[[Omeprazole (Prilosec)]]
+
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, de Boni M, Isaacson PG. Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):575-7. [https://doi.org/10.1016/0140-6736(93)91409-F link to original article] [https://pubmed.ncbi.nlm.nih.gov/8102719 PubMed]
+
# '''EFC10145:''' Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. Epub 2015 Apr 8. [https://doi.org/10.1016/S1470-2045(15)70102-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25864104 PubMed] NCT00699517
−
==Clarithromycin, Metronidzole, PPI {{#subobject:9ihjz5|Regimen=1}}==
+
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:6aubj1|Variant=1}}===
+
===Regimen {{#subobject:2c183b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/oxfordjournals.annonc.a057942 Buesa et al. 1991]
 +
|1984-1986
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(95)90113-2 Bayerdörffer et al. 1995]
+
|[https://doi.org/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]
−
| style="background-color:#91cf61" |Non-randomized
+
|2005-2008
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Dacarbazine_.26_Gemcitabine|Dacarbazine & Gemcitabine]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
−
''This was second-line treatment.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibiotic therapy====
+
====Chemotherapy====
−
*[[Clarithromycin (Biaxin)]] 250 mg PO twice per day
+
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1
−
*[[Metronidazole (Flagyl)]] 400 mg PO three times per day
+
====Supportive therapy====
−
*[[Omeprazole (Prilosec)]] 40 mg PO twice per day
+
*'''Buesa et al. 1991:''' Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.
−
'''10-day course'''
+
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Bayerdörffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M; MALT Lymphoma Study Group. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet. 1995 Jun 24;345(8965):1591-4. [https://doi.org/10.1016/S0140-6736(95)90113-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7783535 PubMed]
+
# Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. High-dose DTIC in advanced soft-tissue sarcomas in the adult: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. [https://doi.org/10.1093/oxfordjournals.annonc.a057942 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1868027 PubMed]
−
## '''Update:''' Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wündisch T, Ehninger G, Stolte M, Bayerdörffer E. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst. 1997 Sep 17;89(18):1350-5. [https://doi.org/10.1093/jnci/89.18.1350 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9308704 PubMed]
+
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.33.6107 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21606430 PubMed] EudraCT 2005-001709-24
−
## '''Update:''' Wündisch T, Thiede C, Morgner A, Dempfle A, Günther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdörffer E, Stolte M, Neubauer A. Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol. 2005 Nov 1;23(31):8018-24. Epub 2005 Oct 3. [https://doi.org/10.1200/jco.2005.02.3903 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16204012 PubMed]
+
==Doxorubicin monotherapy {{#subobject:826f82|Regimen=1}}==
−
==Clarithromycin, Tetracycline, PPI, Bismuth {{#subobject:1ut7a5|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:0qobn1|Variant=1}}===
+
===Regimen variant #1, 75 mg/m<sup>2</sup> {{#subobject:62faa6|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1002/jso.2930110406 Cruz et al. 1979 (COG 7231A)]
 +
|NR
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Actinomycin_.26_Melphalan_88|Actinomycin & Melphalan]]<br> 2. [[#Melphalan_.26_Vincristine_88|Melphalan & Vincristine]]<br> 3. [[#Melphalan_.26_1-aminocyclopentanecarboxylic_acid_77|Melphalan & NSC-1026]]
 +
| style="background-color:#1a9850" |Superior ORR
 
|-
 
|-
−
|[https://doi.org/10.7326/0003-4819-131-2-199907200-00003 Steinbach et al. 1999]
+
|[https://www.ejcancer.com/article/0277-5379(87)90089-7 Mouridsen et al. 1987 (EORTC 62801)]
−
| style="background-color:#91cf61" |Non-randomized
+
|1980-1983
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Epirubicin_monotherapy|Epirubicin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1200/JCO.1995.13.7.1537 Santoro et al. 1995]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|1985-1990
−
====Antibiotic therapy====
+
| style="background-color:#1a9851" |Phase 3 (C)
−
*[[Clarithromycin (Biaxin)]] 500 mg PO three times per day on days 1 to 21
+
|1. [[#Doxorubicin_.26_Ifosfamide|Doxorubicin & Ifosfamide]]<br> 2. [[Stub#CYVADIC|CYVADIC]]
−
*[[Tetracycline (Sumycin)]] 500 mg PO four times per day on days 1 to 21
+
| style="background-color:#ffffbf" |Did not meet endpoints of ORR/DOR/OS
−
*[[Omeprazole (Prilosec)]] or [[Lansoprazole (Prevacid)]]
+
|-
−
*[[Bismuth subsalicylate (Pepto-Bismol)]]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063236/ Nielsen et al. 1998]
−
'''8-week cycle for 2 cycles'''
+
|NR
−
</div></div>
+
| style="background-color:#1a9851" |Phase 3 (C)
−
===References===
+
|[[#Epirubicin_monotherapy|Epirubicin]]
−
#Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. [https://doi.org/10.7326/0003-4819-131-2-199907200-00003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10419446 PubMed]
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
==Metronidazole, Tetracycline, PPI, Bismuth {{#subobject:9ogaz5|Regimen=1}}==
+
|-
−
<div class="toccolours" style="background-color:#eeeeee">
+
| rowspan="2" |[https://doi.org/10.1200/jco.2006.09.7717 Lorigan et al. 2007 (EORTC 62971)]
−
===Regimen {{#subobject:817ty1|Variant=1}}===
+
|rowspan=2|1998-2001
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
−
!style="width: 25%"|Study
+
|1. [[#Ifosfamide_monotherapy|Ifos 3]]
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|2. [[#Ifosfamide_monotherapy|Ifos 9]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(14)70063-4 Judson et al. 2014 (EORTC 62012)]
 +
|2003-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Doxorubicin_.26_Ifosfamide|Doxorubicin & Ifosfamide]]; intensified
 +
| style="background-color:#fee08b" |Might have inferior OS
 
|-
 
|-
−
|[https://doi.org/10.7326/0003-4819-131-2-199907200-00003 Steinbach et al. 1999]
+
|[https://www.ejcancer.com/article/S0959-8049(14)00046-X Blay et al. 2014 (CR015769)]
−
| style="background-color:#91cf61" |Non-randomized
+
|2008-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Trabectedin_monotherapy|Trabectedin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1200/JCO.2016.67.6684 Ryan et al. 2016 (PICASSO III)]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|2010-2012
−
====Antibiotic therapy====
+
| style="background-color:#1a9851" |Phase 3 (C)
−
*[[Metronidazole (Flagyl)]] 500 mg PO three times per day on days 1 to 21
+
|[[#Doxorubicin_.26_Palifosfamide_77|Doxorubicin & Palifosfamide]]
−
*[[Tetracycline (Sumycin)]] 500 mg PO four times per day on days 1 to 21
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
−
*[[Omeprazole (Prilosec)]] or [[Lansoprazole (Prevacid)]]
 
−
*[[Bismuth subsalicylate (Pepto-Bismol)]]
 
−
'''8-week cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Steinbach G, Ford R, Glober G, Sample D, Hagemeister FB, Lynch PM, McLaughlin PW, Rodriguez MA, Romaguera JE, Sarris AH, Younes A, Luthra R, Manning JT, Johnson CM, Lahoti S, Shen Y, Lee JE, Winn RJ, Genta RM, Graham DY, Cabanillas FF. Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue: an uncontrolled trial. Ann Intern Med. 1999 Jul 20;131(2):88-95. [https://doi.org/10.7326/0003-4819-131-2-199907200-00003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10419446 PubMed]
 
−
=Ocular adenexal MALT lymphoma, antibiotic therapy=
 
−
==Doxycycline monotherapy {{#subobject:342bb6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2b7c1c|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[http://jnci.oxfordjournals.org/content/98/19/1375.long Ferreri et al. 2006]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647653/ Tap et al. 2016 (CP15-0806)]
−
|style="background-color:#ffffbe"|Phase 2, <20 patients in this subgroup
+
|2010-2013
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[Soft_tissue_sarcoma_-_historical#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]
 +
| style="background-color:#d73027" |Inferior OS
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2011.41.4466 Ferreri et al. 2012 (IELSG 27)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]
−
|style="background-color:#91cf61"|Phase 2
+
|2010-2014
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 +
| style="background-color:#d9ef8b" |Might have superior PFS
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1016/S1470-2045(17)30381-9 Tap et al. 2017 (TH CR-406/SARC021)]
−
''This treatment was intended for patients with ocular adnexal marginal zone lymphoma (OAMZL), given the association with Chlamydia psittaci.''
+
|2011-2014
−
====Antibiotic therapy====
+
| style="background-color:#1a9851" |Phase 3 (C)
−
*[[Doxycycline]] 100 mg PO twice per day
+
|[[#Doxorubicin_.26_Evofosfamide_77|Doxorubicin & Evofosfamide]]
−
'''3-week course'''
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
−
</div></div>
 
−
===References===
 
−
# Ferreri AJ, Ponzoni M, Guidoboni M, Resti AG, Politi LS, Cortelazzo S, Demeter J, Zallio F, Palmas A, Muti G, Dognini GP, Pasini E, Lettini AA, Sacchetti F, De Conciliis C, Doglioni C, Dolcetti R. Bacteria-eradicating therapy with doxycycline in ocular adnexal MALT lymphoma: a multicenter prospective trial. J Natl Cancer Inst. 2006 Oct 4;98(19):1375-82. [http://jnci.oxfordjournals.org/content/98/19/1375.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17018784 PubMed]
 
−
# '''IELSG 27:''' Ferreri AJ, Govi S, Pasini E, Mappa S, Bertoni F, Zaja F, Montalbán C, Stelitano C, Cabrera ME, Giordano Resti A, Politi LS, Doglioni C, Cavalli F, Zucca E, Ponzoni M, Dolcetti R. Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol. 2012 Aug 20;30(24):2988-94. Epub 2012 Jul 16. Erratum in: J Clin Oncol. 2012 Nov 1;30(31):3903. [https://doi.org/10.1200/jco.2011.41.4466 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22802315 PubMed] NCT01010295
 
−
=Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, first-line therapy=
 
−
''Note: This implies chemotherapy-naive. Some patients in the following studies, especially those with gastric MALT, received H. pylori eradication therapy or radiation prior to chemotherapy.''
 
−
==Bortezomib monotherapy {{#subobject:8dbdb8|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f62265|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675689/ Troch et al. 2009 (Velcade-MALT-Lymphoma)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7139275/ Tap et al. 2020 (ANNOUNCE)]
−
|NR
+
|2015-2018
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Soft_tissue_sarcoma_-_historical#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
 +
''Note: in EORTC 62801, treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m<sup>2</sup>, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician. Patients in CR015769 had translocation-related sarcomas.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.5 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
+
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV bolus once on day 1
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV immediately before [[Bortezomib (Velcade)]]
+
*CP15-0806, optional: [[Dexrazoxane (Zinecard)]] (dose not specified) IV once on day 1
−
*500 mL NS after [[Bortezomib (Velcade)]]
+
'''21-day cycle for up to 6 to 8 cycles (see note)'''
−
'''21-day cycle for up to 8 cycles'''
+
</div></div><br>
−
</div></div>
 
−
===References===
 
−
# '''Velcade-MALT-Lymphoma:''' Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. Epub 2009 Mar 31. [http://www.haematologica.org/content/94/5/738.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675689/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19336742 PubMed] NCT00373906
 
−
==Bendamustine & Rituximab (BR) {{#subobject:ac973d|Regimen=1}}==
 
−
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:7926ac|Variant=1}}===
+
===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:fcfa1c|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 226: Line 298:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1016/S2352-3026(14)00021-0 Salar et al. 2014 (GELTAMO MALT2008-01)]
+
| rowspan="2" |[https://doi.org/10.1200/JCO.1993.11.7.1269 Edmonson et al. 1993]
−
|2009-2011
+
|rowspan=2|1987-1990
−
|style="background-color:#91cf61"|Phase 2
+
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
−
|style="background-color:#d3d3d3"|
+
|1. [[#Doxorubicin_.26_Ifosfamide|Doxorubicin & Ifosfamide]]
−
|style="background-color:#d3d3d3"|
+
| style="background-color:#fc8d59" |Seems to have inferior ORR
 +
|-
 +
|2. [[#MAC_88|MAC]]
 +
| style="background-color:#fee08b" |Might have inferior ORR
 
|-
 
|-
 
|}
 
|}
−
''Note: treatment in MALT2008-01 was response adapted; patients with CR after 3 cycles received a total of 4 cycles, whereas patients with PR after 3 cycles received a total of 6 cycles.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Doxorubicin (Adriamycin)]] 80 mg/m<sup>2</sup> IV bolus once on day 1
−
====Targeted therapy====
+
'''21-day cycles'''
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*Antiemetics, antipyretics, and antibiotics according to local standard of care
 
−
*Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [https://doi.org/10.1200/jco.2006.06.4451 ASCO guidelines] (2006)
 
−
'''28-day cycle for up to 8 cycles (see note)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GELTAMO MALT2008-01:''' Salar A, Domingo-Domenech E, Panizo C, Nicolás C, Bargay J, Muntañola A, Canales M, Bello JL, Sancho JM, Tomás JF, Rodríguez MJ, Peñalver FJ, Grande C, Sánchez-Blanco JJ, Palomera L, Arranz R, Conde E, García M, García JF, Caballero D, Montalbán C; Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO). First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2014 Dec;1(3):e104-11. Epub 2014 Nov 19. [https://doi.org/10.1016/S2352-3026(14)00021-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27029228 PubMed] NCT01015248
+
# '''COG 7231-A:''' Cruz AB Jr, Thames EA Jr, Aust JB, Metter G, Ramirez G, Fletcher WS, Altman SJ, Frelick RW, Hill GJ 2nd. Combination chemotherapy for soft-tissue sarcomas: a phase III study. J Surg Oncol. 1979;11(4):313-23. [https://doi.org/10.1002/jso.2930110406 link to original article] [https://pubmed.ncbi.nlm.nih.gov/376950 PubMed]
−
## '''Update:''' Salar A, Domingo-Domenech E, Panizo C, Nicolás C, Bargay J, Muntañola A, Canales M, Bello JL, Sancho JM, Tomás JF, Rodríguez MJ, Peñalver J, Grande C, Sánchez-Blanco JJ, Palomera L, Arranz R, Conde E, García M, García JF, Caballero D, Montalbán C. Long-term results of a phase 2 study of rituximab and bendamustine for mucosa-associated lymphoid tissue lymphoma. Blood. 2017 Oct 12;130(15):1772-1774. Epub 2017 Aug 11. [http://www.bloodjournal.org/content/130/15/1772.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/28801448 PubMed]
+
# '''EORTC 62801:''' Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Adriamycin versus epirubicin in advanced soft tissue sarcomas: a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [https://www.ejcancer.com/article/0277-5379(87)90089-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3479329 PubMed]
−
==Chlorambucil monotherapy {{#subobject:10e826|Regimen=1}}==
+
# Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269-75. [https://doi.org/10.1200/JCO.1993.11.7.1269 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8315424 PubMed]
 +
# Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa J, Casali P, Spooner D, Rankin E, Kirkpatrick A, van Glabbeke M, van Oosterom A; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537-45. [https://doi.org/10.1200/JCO.1995.13.7.1537 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7602342 PubMed]
 +
# Nielsen OS, Dombernowsky P, Mouridsen H, Crowther D, Verweij J, Buesa J, Steward W, Daugaard S, van Glabbeke M, Kirkpatrick A, Tursz T; [[Study_Groups#EORTC|EORTC]] soft tissue and bone sarcoma group. High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas: a study of the EORTC soft tissue and bone sarcoma group. Br J Cancer. 1998 Dec;78(12):1634-9. [https://doi.org/10.1038/bjc.1998.735 linkt o original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063236/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9862576 PubMed]
 +
# '''Meta-analysis:''' Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. [http://www.hindawi.com/journals/srcm/2000/149793/abs/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395439/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18521288 PubMed]
 +
# '''EORTC 62971:''' Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [https://doi.org/10.1200/jco.2006.09.7717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17634494 PubMed] NCT00003212
 +
# '''CR015769:''' Blay JY, Leahy MG, Nguyen BB, Patel SR, Hohenberger P, Santoro A, Staddon AP, Penel N, Piperno-Neumann S, Hendifar A, Lardelli P, Nieto A, Alfaro V, Chawla SP. Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. Eur J Cancer. 2014 Apr;50(6):1137-47. Epub 2014 Feb 7. [https://www.ejcancer.com/article/S0959-8049(14)00046-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24512981 PubMed] NCT00796120
 +
# '''EORTC 62012:''' Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. [https://doi.org/10.1016/S1470-2045(14)70063-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24618336 PubMed] NCT00061984
 +
# '''CP15-0806:''' Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. [https://doi.org/10.1016/S0140-6736(16)30587-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647653/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27291997 PubMed] NCT01185964
 +
# '''PICASSO III:''' Ryan CW, Merimsky O, Agulnik M, Blay JY, Schuetze SM, Van Tine BA, Jones RL, Elias AD, Choy E, Alcindor T, Keedy VL, Reed DR, Taub RN, Italiano A, Garcia Del Muro X, Judson IR, Buck JY, Lebel F, Lewis JJ, Maki RG, Schöffski P. PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma. J Clin Oncol. 2016 Nov 10;34(32):3898-3905. Epub 2016 Sep 30. [https://doi.org/10.1200/JCO.2016.67.6684 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27621408 PubMed] NCT01168791
 +
# '''TH CR-406/SARC021:''' Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. Epub 2017 Jun 23. [https://doi.org/10.1016/S1470-2045(17)30381-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28651927 PubMed] NCT01440088
 +
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [https://doi.org/10.1016/S1470-2045(17)30622-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28882536 PubMed] ISRCTN07742377
 +
# '''ANNOUNCE:''' Tap WD, Wagner AJ, Schöffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, Yen CC, Abdul Razak AR, Spira A, Kawai A, Le Cesne A, Van Tine BA, Naito Y, Park SH, Fedenko A, Pápai Z, Soldatenkova V, Shahir A, Mo G, Wright J, Jones RL; ANNOUNCE Investigators. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1266-1276. [https://doi.org/10.1001/jama.2020.1707 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7139275/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32259228 PubMed] NCT02451943
 +
==Epirubicin monotherapy {{#subobject:d976a5|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:8fc8cb|Variant=1}}===
+
===Regimen {{#subobject:a1dd30|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 257: Line 338:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|rowspan=2|[https://doi.org/10.1200/jco.2011.40.6272 Zucca et al. 2013 (IELSG-19)]
+
|[https://www.ejcancer.com/article/0277-5379(87)90089-7 Mouridsen et al. 1987 (EORTC 62801)]
−
|rowspan=2|2003-2005
+
|1980-1983
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc)
+
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
−
|1. [[#Chlorambucil_.26_Rituximab_.28RClb.29|Chlorambucil & Rituximab]]
+
|[[#Doxorubicin_monotherapy|Doxorubicin]]
−
|style="background-color:#fc8d59"|Seems to have inferior PFS<sup>1</sup>
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
|-
 
−
|2. [[#Rituximab_monotherapy|Rituximab]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS<sup>1</sup>
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy is based on the 2017 update.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 6 mg/m<sup>2</sup> PO once per day
+
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV bolus once on day 1
−
'''6-week course'''
+
'''21-day cycle for up to 7 cycles (cumulative epirubicin dosage of 550 mg/m<sup>2</sup>)''' (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with SD or better: [[#Chlorambucil_monotherapy_2|Chlorambucil]] consolidation
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''IELSG-19:''' Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 randomized study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [https://doi.org/10.1200/jco.2011.40.6272 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23295789 PubMed] NCT00210353
+
# '''EORTC 62801:''' Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R. Adriamycin versus epirubicin in advanced soft tissue sarcomas: a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [https://www.ejcancer.com/article/0277-5379(87)90089-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3479329 PubMed]
−
<!-- # '''Abstract:''' E. Zucca, A. Conconi, G. Martinelli, A. Tucci, U. Vitolo, E. Russo, B. Coiffier, H. Ghesquieres, F. Morschhauser, R. Pettengell, G. Pinotti, L. Devizzi, R. Bouabdallah, C. Copie-Bergman, S. Pileri, A. Jack, E. Campo, A. Lopez-Guillermo, P. W. Johnson, C. Thieblemont. CHLORAMBUCIL PLUS RITUXIMAB PRODUCES BETTER EVENTFREE AND PROGRESSION-FREE SURVIVAL IN COMPARISON WITH CHLORAMBUCIL OR RITUXIMAB ALONE IN EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT LYMPHOMA): FINAL RESULTS OF THE IELSG-19 STUDY. XII INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Abstract 007 (2013). [http://www.ielsg.org/documents/ielsg19lug13.pdf link to abstract] -->
+
==Ifosfamide monotherapy {{#subobject:88d059|Regimen=1}}==
−
## '''Update:''' Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. [https://doi.org/10.1200/JCO.2016.70.6994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28355112 PubMed]
 
−
==Chlorambucil & Rituximab (RClb) {{#subobject:346328|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:664c41|Variant=1}}===
+
===Regimen variant #1, short infusion (Ifos 3) {{#subobject:89c8f1|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 291: Line 362:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2011.40.6272 Zucca et al. 2013 (IELSG-19)]
+
| rowspan="2" |[https://doi.org/10.1200/jco.2006.09.7717 Lorigan et al. 2007 (EORTC 62971)]
−
|2003-2005
+
|rowspan=2|1998-2001
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
+
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]<br> 2. [[#Rituximab_monotherapy|Rituximab]]
+
|1. [[#Doxorubicin_monotherapy|Doxorubicin]]
−
|style="background-color:#91cf60"|Seems to have superior PFS<sup>1</sup> <br>(HR 0.62, 95% CI 0.42-0.93)
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|2. [[#Ifosfamide_monotherapy|Ifosfamide]]; Ifos 9
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy is based on the 2017 update.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 6 mg/m<sup>2</sup> PO once per day
+
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, mixed with mesna in 1 liter of normal saline
−
====Targeted therapy====
+
====Supportive therapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV bolus once on day 1, '''given immediately prior to mesna/ifosfamide infusion''', then 1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given with [[Ifosfamide (Ifex)]], then 1200 mg/m<sup>2</sup> IV twice per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna
−
'''6-week course'''
+
**An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO twice per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna
−
</div>
+
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
−
<div class="toccolours" style="background-color:#cbd5e7">
+
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion
−
====Subsequent treatment====
+
'''21-day cycle for up to 6 cycles'''
−
*Patients with SD or better: [[#Chlorambucil_.26_Rituximab_.28RClb.29_2|Chlorambucil & rituximab]] consolidation
+
</div></div><br>
−
</div></div>
 
−
===References===
 
−
# '''IELSG-19:''' Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 randomized study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [https://doi.org/10.1200/jco.2011.40.6272 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23295789 PubMed] NCT00210353
 
−
<!-- # '''Abstract:''' E. Zucca, A. Conconi, G. Martinelli, A. Tucci, U. Vitolo, E. Russo, B. Coiffier, H. Ghesquieres, F. Morschhauser, R. Pettengell, G. Pinotti, L. Devizzi, R. Bouabdallah, C. Copie-Bergman, S. Pileri, A. Jack, E. Campo, A. Lopez-Guillermo, P. W. Johnson, C. Thieblemont. CHLORAMBUCIL PLUS RITUXIMAB PRODUCES BETTER EVENTFREE AND PROGRESSION-FREE SURVIVAL IN COMPARISON WITH CHLORAMBUCIL OR RITUXIMAB ALONE IN EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT LYMPHOMA): FINAL RESULTS OF THE IELSG-19 STUDY. XII INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Abstract 007 (2013). [http://www.ielsg.org/documents/ielsg19lug13.pdf link to abstract] -->
 
−
## '''Update:''' Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. [https://doi.org/10.1200/JCO.2016.70.6994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28355112 PubMed]
 
−
==Cladribine monotherapy {{#subobject:b1fc89|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:501943|Variant=1}}===
+
===Regimen variant #2, continuous infusion (Ifos 9) {{#subobject:ad63a|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2006.09.7717 Lorigan et al. 2007 (EORTC 62971)]
 +
|rowspan=2|1998-2001
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Doxorubicin_monotherapy|Doxorubicin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2002.05.117 Jäger et al. 2002]
+
|2. [[#Ifosfamide_monotherapy|Ifosfamide]]; Ifos 3
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cladribine (Leustatin)]] 0.12 mg/kg IV over 2 hours once per day on days 1 to 5
+
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1, '''given with mesna''' (total dose per cycle: 9000 mg/m<sup>2</sup>)
−
'''28-day cycle for 4 to 6 cycles'''
+
**Each day's dose is mixed with mesna in 3 liters of normal saline
−
====Dose modifications====
+
====Supportive therapy====
−
*"In case of a persisting nadir of the WBC count less than or equal to 4.0 × 10<sup>9</sup>/L (or ANC less than or equal to 1500/uL) and/or the platelets less than or equal to 100 × 10<sup>9</sup>/L, the next treatment cycle was delayed by 1 week until achieving normal values and then treatment was administered at a reduced dose of 0.1 mg/kg body weight."
+
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV bolus once on day 1, '''immediately prior to mesna/ifosfamide infusion''', then 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, starting on day 1, given with [[Ifosfamide (Ifex)]], then 1800 mg/m<sup>2</sup> IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna
−
</div></div>
+
**An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna
−
===References===
+
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
−
# Jäger G, Neumeister P, Brezinschek R, Hinterleitner T, Fiebiger W, Penz M, Neumann HJ, Mlineritsch B, DeSantis M, Quehenberger F, Chott A, Beham-Schmid C, Höfler G, Linkesch W, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type with cladribine: a phase II study. J Clin Oncol. 2002 Sep 15;20(18):3872-7. [https://doi.org/10.1200/jco.2002.05.117 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12228207 PubMed]
+
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion
−
==Cladribine & Rituximab {{#subobject:3ac33|Regimen=1}}==
+
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:bd61ae|Variant=1}}===
+
===Regimen variant #3 {{#subobject:210d2d|Variant=1}}===
−
{| class="wikitable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
 
!style="width: 33%"|Years of enrollment
 
!style="width: 33%"|Years of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561434/ Troch et al. 2012 (AGMT MALT)]
+
|[https://www.ejcancer.com/article/S0959-8049(02)00491-4 van Oosterom et al. 2002]
−
|2008-2010
+
|1992-1994
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 4
+
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 3, dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed with mesna in an additional 1 liter of dextrose/saline
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Acetaminophen (Tylenol)]] 1000 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
+
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV bolus once on day 1, '''immediately prior to mesna/ifosfamide infusion''', then 1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, '''given with [[Ifosfamide (Ifex)]]''', then 500 mg/m<sup>2</sup> IV twice per day on days 1 to 3, '''given at 4 and 8 hours after completion of ifosfamide and mesna'''
−
*[[:Category:Antihistamines|Antihistamine]] IV once on day 1, prior to [[Rituximab (Rituxan)]]
+
*"[[:Category:Emesis_prevention|Antiemetics]] were prescribed according to local conventions"
−
*One of the following:
+
*1 liter of fluid PO twice per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna
−
**[[Ondansetron (Zofran)]] IV once per day on days 1 to 4, prior to [[Cladribine (Leustatin)]]
+
'''21-day cycle for at least 2 cycles, except in cases of rapid disease progression'''
−
**[[Tropisetron (Navoban)]] IV once per day on days 1 to 4, prior to [[Cladribine (Leustatin)]]
 
−
'''21-day cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''AGMT MALT:''' Troch M, Kiesewetter B, Willenbacher W, Willenbacher E, Zebisch A, Linkesch W, Fridrik M, Müllauer L, Greil R, Raderer M. Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie. Haematologica. 2013 Feb;98(2):264-8. Epub 2012 Sep 14. [http://www.haematologica.org/content/98/2/264.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561434/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22983582 PubMed] NCT00656812
+
# van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 [https://www.ejcancer.com/article/S0959-8049(02)00491-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12460784 PubMed] content property of [http://hemonc.org HemOnc.org]
−
==Fludarabine and Rituximab (FR) {{#subobject:413f96|Regimen=1}}==
+
# '''EORTC 62971:''' Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [https://doi.org/10.1200/jco.2006.09.7717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17634494 PubMed] NCT00003212
−
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
+
==Pazopanib monotherapy {{#subobject:644c8f|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:8551bb|Variant=1}}===
+
===Regimen {{#subobject:332a64|Variant=1}}===
−
{| class="wikitable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 33%"|Study
+
!style="width: 20%"|Study
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.24605 Salar et al. 2009]
+
|[https://doi.org/10.1016/S0140-6736(12)60651-5 van der Graaf et al. 2012 (PALETTE)]
−
|style="background-color:#91cf61"|Phase 2
+
|2008-2010
−
| style="background-color:#f7fcfd" |ORR: 100%
+
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Soft_tissue_sarcoma_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.6 vs 1.6 mo<br>(HR 0.31, 95% CI 0.24-0.40)
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV (or 40 mg/m<sup>2</sup> PO) once per day on days 1 to 5
 
−
**Patients with gastric lymphoma received the cycle 1 dose intravenously to guarantee drug absorption
 
−
**Patients greater than 70 years old: same dose, but only once per day on days 1 to 3
 
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
*[[Pazopanib (Votrient)]] 800 mg PO once per day
−
====Supportive therapy====
+
'''Continued indefinitely'''
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole]] prophylaxis (dose/schedule not listed) per physician preference
 
−
*No routine antiviral prophylaxis or G-CSF use
 
−
'''28-day cycle for 4 to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Salar A, Domingo-Domenech E, Estany C, Canales MA, Gallardo F, Servitje O, Fraile G, Montalbán C. Combination therapy with rituximab and intravenous or oral fludarabine in the first-line, systemic treatment of patients with extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type. Cancer. 2009 Nov 15;115(22):5210-7. [https://doi.org/10.1002/cncr.24605 link to orginal article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19672998 PubMed]
+
# '''PALETTE:''' van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [https://doi.org/10.1016/S0140-6736(12)60651-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22595799 PubMed] NCT00753688
−
==Lenalidomide monotherapy {{#subobject:4f6ca7|Regimen=1}}==
+
## '''Subgroup analysis:''' Kawai A, Araki N, Hiraga H, Sugiura H, Matsumine A, Ozaki T, Ueda T, Ishii T, Esaki T, Machida M, Fukasawa N. A randomized, double-blind, placebo-controlled, phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup. Jpn J Clin Oncol. 2016 Mar;46(3):248-53. Epub 2016 Feb 10. [https://academic.oup.com/jjco/article/46/3/248/2384950 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777611/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26864131 PubMed]
 +
==Regorafenib monotherapy {{#subobject:c9fc2c|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:43bad7|Variant=1}}===
+
===Regimen {{#subobject:b5ff4e|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659944/ Kiesewetter et al. 2012 (LEN-MALT)]
+
|[https://doi.org/10.1016/S1470-2045(16)30507-1 Mir et al. 2016 (REGOSARC)]
−
|style="background-color:#ffffbe"|Phase 2, <20 patients reported
+
|2013-2014
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|[[Soft_tissue_sarcoma_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#1a9850" |Superior PFS
 
|-
 
|-
 
|}
 
|}
 +
''Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
+
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
−
====Supportive therapy====
+
'''28-day cycles'''
−
*[[Aspirin]] 100 mg PO once per day
 
−
'''28-day cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LEN-MALT:''' Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica. 2013 Mar;98(3):353-6. Epub 2012 Aug 16. [http://www.haematologica.org/content/98/3/353.long link to orginal article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659944/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22899582 PubMed] NCT00923663
+
# '''REGOSARC:''' Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [https://doi.org/10.1016/S1470-2045(16)30507-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27751846 PubMed] NCT01900743
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:c8fa86|Regimen=1}}==
+
==Temozolomide monotherapy {{#subobject:5929ed|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:38dadd|Variant=1}}===
+
===Regimen variant #1, 5 out of 28 days {{#subobject:63d3d8|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/129/3/383.long Kiesewetter et al. 2016 (AGMT MALT-2)]
+
|[https://doi.org/10.1002/cncr.11730 Talbot et al. 2003]
−
|style="background-color:#91cf61"|Phase 2
+
|1998-2000
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
 +
''Note: patients on study could be reconsented to receive therapy beyond 1 year. Treatment given on an empty stomach, and doses rounded up if needed to next available dosage based on capsule doses.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
+
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once on day 1, then 12 hours later, 90 mg/m<sup>2</sup> PO every 12 hours on days 1 to 5 (total of 10 doses per cycle)
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
====Supportive therapy====
−
'''28-day cycle for up to 8 to 12 cycles'''
+
*[[:Category:Emesis_prevention|Antiemetics]] "prescribed as clinically indicated by the treating physician"
−
</div></div>
+
'''28-day cycle for up to 13 cycles (1 year)'''
−
===References===
+
</div></div><br>
−
# '''AGMT MALT-2:''' Kiesewetter B, Willenbacher E, Willenbacher W, Egle A, Neumeister P, Voskova D, Mayerhoefer ME, Simonitsch-Klupp I, Melchardt T, Greil R, Raderer M; AGMT Investigators. A phase 2 study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma. Blood. 2017 Jan 19;129(3):383-385. Epub 2016 Nov 22. [http://www.bloodjournal.org/content/129/3/383.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27879257 PubMed] NCT01611259
 
−
==MCP {{#subobject:1cc3da|Regimen=1}}==
 
−
MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:2421bc|Variant=1}}===
+
===Regimen variant #2, 6 out of 9 weeks {{#subobject:892d65|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdg492 Wöhrer et al. 2003]
+
|[https://doi.org/10.1002/cncr.21384 Garcia del Muro et al. 2005]
−
|style="background-color:#ffffbe"|Retrospective
+
|1999-2001
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
+
''Note: Initial dose used in the study was 75 mg/m<sup>2</sup>, but due to lack of toxicity, protocol was amended to use 100 mg/m<sup>2</sup> doses.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 42, no food 1 hour before and after temozolomide doses
−
*[[Chlorambucil (Leukeran)]] 3 mg/m<sup>2</sup> PO three times per day on days 1 to 5
+
====Supportive therapy====
−
====Glucocorticoid therapy====
+
*"[[:Category:Emesis_prevention|Antiemetics]], mainly oral [[Metoclopramide (Reglan)]] and [[Ondansetron (Zofran)]], were prescribed as clinically indicated by the treating physician"
−
*[[Prednisone (Sterapred)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
'''9-week cycle for up to 3 cycles'''
−
'''28-day cycle for up to 8 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Retrospective:''' Wöhrer S, Drach J, Hejna M, Scheithauer W, Dirisamer A, Püspök A, Chott A, Raderer M. Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP). Ann Oncol. 2003 Dec;14(12):1758-61. [https://doi.org/10.1093/annonc/mdg492 link to orginal article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14630681 PubMed]
+
# Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. [https://doi.org/10.1002/cncr.11730 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14584078 PubMed]
−
==Rituximab monotherapy {{#subobject:c82d07|Regimen=1}}==
+
# Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. [https://doi.org/10.1002/cncr.21384 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16134177 PubMed]
 +
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:c20616|Variant=1}}===
+
===Regimen #1, 1.2 mg/m<sup>2</sup> {{#subobject:33de2b|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 462: Line 540:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/102/8/2741.long Conconi et al. 2003 (IELSG 6)]
+
|[https://doi.org/10.1016/S1470-2045(15)70098-7 Kawai et al. 2015]
−
|2000-2001
+
|2012-2014
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
−
|style="background-color:#d3d3d3"|
+
|[[Soft_tissue_sarcoma_-_null_regimens#Placebo|Placebo]]
−
|style="background-color:#d3d3d3"|
+
| style="background-color:#1a9850" |Superior PFS
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2005.08.128 Martinelli et al. 2005]
+
|}
−
|NR
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|style="background-color:#91cf61"|Phase 2
+
====Chemotherapy====
−
|style="background-color:#d3d3d3"|
+
*[[Trabectedin (Yondelis)]] 1.2 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
−
|style="background-color:#d3d3d3"|
+
'''21-day cycles'''
−
|-
+
<div class="toccolours" style="background-color:#eeeeee">
−
|rowspan=2|[https://doi.org/10.1200/jco.2011.40.6272 Zucca et al. 2013 (IELSG-19)]
+
===Regimen #2, 1.5 mg/m<sup>2</sup> {{#subobject:33523b|Variant=1}}===
−
|rowspan=2|2003-2005
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+
!style="width: 20%"|Study
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]
+
!style="width: 20%"|Years of enrollment
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of EFS
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|2. [[#Chlorambucil_.26_Rituximab_.28RClb.29|Chlorambucil & Rituximab]]
+
|[https://doi.org/10.1016/j.annonc.2021.04.014 Le Cesne et al. 2021 (T-SAR)]
−
|style="background-color:#fc8d59"|Seems to have inferior PFS
+
|2015
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Soft_tissue_sarcoma_-_null_regimens#Best_supportive_care|Best supportive care]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 3.1 vs 1.5 mo<br>(HR 0.39, 95% CI 0.24-0.64)
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
−
====Supportive therapy====
+
'''21-day cycles'''
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
'''4-week course'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. [http://www.bloodjournal.org/content/102/8/2741.long link to orginal article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12842999 PubMed] content property of [http://hemonc.org HemOnc.org]
+
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [https://doi.org/10.1016/S1470-2045(15)70098-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25795406 PubMed] JapicCTI-121850
−
# Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. [https://doi.org/10.1200/jco.2005.08.128 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15668468 PubMed]
+
# '''T-SAR:''' Le Cesne A, Blay JY, Cupissol D, Italiano A, Delcambre C, Penel N, Isambert N, Chevreau C, Bompas E, Bertucci F, Chaigneau L, Piperno-Neumann S, Salas S, Rios M, Guillemet C, Bay JO, Ray-Coquard I, Haddag L, Bonastre J, Kapso R, Fraslin A, Bouvet N, Mir O, Foulon S. A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial. Ann Oncol. 2021 Aug;32(8):1034-1044. Epub 2021 Apr 29. [https://doi.org/10.1016/j.annonc.2021.04.014 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33932507/ PubMed] NCT02672527
−
# '''IELSG-19:''' Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 randomized study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [https://doi.org/10.1200/jco.2011.40.6272 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23295789 PubMed] NCT00210353
+
=Locally advanced or metastatic disease, combination regimens=
−
<!-- # '''Abstract:''' E. Zucca, A. Conconi, G. Martinelli, A. Tucci, U. Vitolo, E. Russo, B. Coiffier, H. Ghesquieres, F. Morschhauser, R. Pettengell, G. Pinotti, L. Devizzi, R. Bouabdallah, C. Copie-Bergman, S. Pileri, A. Jack, E. Campo, A. Lopez-Guillermo, P. W. Johnson, C. Thieblemont. CHLORAMBUCIL PLUS RITUXIMAB PRODUCES BETTER EVENTFREE AND PROGRESSION-FREE SURVIVAL IN COMPARISON WITH CHLORAMBUCIL OR RITUXIMAB ALONE IN EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT LYMPHOMA): FINAL RESULTS OF THE IELSG-19 STUDY. XII INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Abstract 007 (2013). [http://www.ielsg.org/documents/ielsg19lug13.pdf link to abstract] -->
+
==Dacarbazine & Doxorubicin {{#subobject:9085a9|Regimen=1}}==
−
## '''Update:''' Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. [https://doi.org/10.1200/JCO.2016.70.6994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28355112 PubMed]
+
AD: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>D</u>'''acarbazine
−
=Consolidation after first-line therapy=
 
−
==Chlorambucil monotherapy {{#subobject:0c174d|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:9bb2aa|Variant=1}}===
+
===Regimen {{#subobject:a9a5c2|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2011.40.6272 Zucca et al. 2013 (IELSG-19)]
+
|[https://doi.org/10.1200/JCO.1987.5.6.851 Baker et al. 1987 (SWOG S7613)]
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
+
|1976-1979
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cyclophosphamide.2C_Dacarbazine.2C_Doxorubicin_99|AD & Cyclophosphamide]]<br> 2. [[#Dacarbazine.2C_Dactinomycin.2C_Doxorubicin_99|AD & Dactinomycin]]
 +
| style="background-color:#ffffbf" |Did not meet endpoints of RR/OS
 +
|-
 +
|[https://academic.oup.com/jnci/article-abstract/83/13/926/988180 Zalupski et al. 1991]
 +
|1980-1986
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Dacarbazine_.26_Doxorubicin|Dacarbazine & Doxorubicin]]; CI
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
 +
|-
 +
|[https://doi.org/10.1200/JCO.1993.11.7.1276 Antman et al. 1993]
 +
|1987-1989
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#MAID|MAID]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#cbd5e8">
+
''<sup>1</sup>In Antman et al. 1993, although the experimental arm seemed to have superior TTP, this arm seemed to have superior OS.''<br>
−
====Preceding treatment====
+
''Here for historic purposes.''
−
*[[#Chlorambucil_monotherapy|Chlorambucil]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 14
+
*[[Dacarbazine (DTIC)]]
−
'''28-day cycle for up to 4 cycles'''
+
*[[Doxorubicin (Adriamycin)]]
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''IELSG-19:''' Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 randomized study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [https://doi.org/10.1200/jco.2011.40.6272 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23295789 PubMed] NCT00210353
+
# '''SWOG S7613:''' Baker LH, Frank J, Fine G, Balcerzak SP, Stephens RL, Stuckey WJ, Rivkin S, Saiki J, Ward JH. Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial: a phase III, Southwest Oncology Group Study (7613). J Clin Oncol. 1987 Jun;5(6):851-61. [https://doi.org/10.1200/JCO.1987.5.6.851 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3295129 PubMed]
−
<!-- # '''Abstract:''' E. Zucca, A. Conconi, G. Martinelli, A. Tucci, U. Vitolo, E. Russo, B. Coiffier, H. Ghesquieres, F. Morschhauser, R. Pettengell, G. Pinotti, L. Devizzi, R. Bouabdallah, C. Copie-Bergman, S. Pileri, A. Jack, E. Campo, A. Lopez-Guillermo, P. W. Johnson, C. Thieblemont. CHLORAMBUCIL PLUS RITUXIMAB PRODUCES BETTER EVENTFREE AND PROGRESSION-FREE SURVIVAL IN COMPARISON WITH CHLORAMBUCIL OR RITUXIMAB ALONE IN EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT LYMPHOMA): FINAL RESULTS OF THE IELSG-19 STUDY. XII INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Abstract 007 (2013). [http://www.ielsg.org/documents/ielsg19lug13.pdf link to abstract] -->
+
# Zalupski M, Metch B, Balcerzak S, Fletcher WS, Chapman R, Bonnet JD, Weiss GR, Ryan J, Benjamin RS, Baker LH; [[Study_Groups#SWOG|SWOG]]. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Jul 3;83(13):926-32. [https://academic.oup.com/jnci/article-abstract/83/13/926/988180 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2067035 PubMed]
−
## '''Update:''' Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. [https://doi.org/10.1200/JCO.2016.70.6994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28355112 PubMed]
+
# Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, Doroshow JH, Aisner J, Pugh RP, Weiss RB, Cooper BA, Clamond GH, Baker LH. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. [https://doi.org/10.1200/JCO.1993.11.7.1276 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8315425 PubMed]
−
==Chlorambucil & Rituximab (RClb) {{#subobject:e72abc|Regimen=1}}==
+
==Dacarbazine & Gemcitabine {{#subobject:cd9068|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:594e34|Variant=1}}===
+
===Regimen {{#subobject:9aaddf|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2011.40.6272 Zucca et al. 2013 (IELSG-19)]
+
|[https://doi.org/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
+
|2005-2008
 +
| style="background-color:#ffffbe" |Randomized Phase 2, <20 pts in this subgroup (E-esc)
 +
|[[#Dacarbazine_monotherapy|Dacarbazine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Chlorambucil_.26_Rituximab_.28RClb.29|Chlorambucil & Rituximab]] induction
 
−
</div>
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 14
+
*[[Dacarbazine (DTIC)]] 500 mg/m<sup>2</sup> IV over 20 minutes once on day 1, '''given second'''
−
====Targeted therapy====
+
*[[Gemcitabine (Gemzar)]] 1800 mg/m<sup>2</sup> IV at fixed dosed rate over 3 hours once on day 1, '''given first'''
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
'''14-day cycle for at least 12 cycles'''
−
'''28-day cycle for up to 4 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''IELSG-19:''' Zucca E, Conconi A, Laszlo D, López-Guillermo A, Bouabdallah R, Coiffier B, Sebban C, Jardin F, Vitolo U, Morschhauser F, Pileri SA, Copie-Bergman C, Campo E, Jack A, Floriani I, Johnson P, Martelli M, Cavalli F, Martinelli G, Thieblemont C. Addition of rituximab to chlorambucil produces superior event-free survival in the treatment of patients with extranodal marginal-zone B-cell lymphoma: 5-year analysis of the IELSG-19 randomized study. J Clin Oncol. 2013 Feb 10;31(5):565-72. Epub 2013 Jan 7. [https://doi.org/10.1200/jco.2011.40.6272 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23295789 PubMed] NCT00210353
+
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.33.6107 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21606430 PubMed] EudraCT 2005-001709-24
−
<!-- # '''Abstract:''' E. Zucca, A. Conconi, G. Martinelli, A. Tucci, U. Vitolo, E. Russo, B. Coiffier, H. Ghesquieres, F. Morschhauser, R. Pettengell, G. Pinotti, L. Devizzi, R. Bouabdallah, C. Copie-Bergman, S. Pileri, A. Jack, E. Campo, A. Lopez-Guillermo, P. W. Johnson, C. Thieblemont. CHLORAMBUCIL PLUS RITUXIMAB PRODUCES BETTER EVENTFREE AND PROGRESSION-FREE SURVIVAL IN COMPARISON WITH CHLORAMBUCIL OR RITUXIMAB ALONE IN EXTRANODAL MARGINAL ZONE B-CELL LYMPHOMA (MALT LYMPHOMA): FINAL RESULTS OF THE IELSG-19 STUDY. XII INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Abstract 007 (2013). [http://www.ielsg.org/documents/ielsg19lug13.pdf link to abstract] -->
+
==Docetaxel & Gemcitabine {{#subobject:1e718f|Regimen=1}}==
−
## '''Update:''' Zucca E, Conconi A, Martinelli G, Bouabdallah R, Tucci A, Vitolo U, Martelli M, Pettengell R, Salles G, Sebban C, Guillermo AL, Pinotti G, Devizzi L, Morschhauser F, Tilly H, Torri V, Hohaus S, Ferreri AJM, Zachée P, Bosly A, Haioun C, Stelitano C, Bellei M, Ponzoni M, Moreau A, Jack A, Campo E, Mazzucchelli L, Cavalli F, Johnson P, Thieblemont C. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017 Jun 10;35(17):1905-1912. Epub 2017 Mar 29. [https://doi.org/10.1200/JCO.2016.70.6994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28355112 PubMed]
 
−
==Observation==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen===
+
===Regimen {{#subobject:2898f9|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 559: Line 652:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659366/ Hancock et al. 2008 (LY03)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]
−
|1995-2001
+
|2010-2014
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
−
|[[#Chlorambucil_monotherapy_2|Chlorambucil]]
+
|[[#Doxorubicin_monotherapy|Doxorubicin]]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RR
+
| style="background-color:#fee08b" |Might have inferior PFS
 
|-
 
|-
 
|}
 
|}
−
''No further treatment.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
<div class="toccolours" style="background-color:#cbd5e8">
+
====Chemotherapy====
−
====Preceding treatment====
+
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''
−
*[[#Helicobacter_pylori_eradication_therapy|H. pylori eradication therapy]]
+
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]] 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])
 +
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
 +
*One of the following growth factors (varies depending on reference):
 +
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
 +
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10
 +
'''21-day cycle for 6 to 8 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LY03:''' Hancock BW, Qian W, Linch D, Delchier JC, Smith P, Jakupovic I, Burton C, Souhami R, Wotherspoon A, Copie-Bergman C, Capella C, Traulle C, Levy M, Cortelazzo S, Ferreri AJ, Ambrosetti A, Pinotti G, Martinelli G, Vitolo U, Cavalli F, Gisselbrecht C, Zucca E. Chlorambucil versus observation after anti-Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial. Br J Haematol. 2009 Feb;144(3):367-75. Epub 2008 Nov 22. [https://doi.org/full/10.1111/j.1365-2141.2008.07486.x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659366/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19036078 PubMed] NCT00003617
+
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [https://doi.org/10.1016/S1470-2045(17)30622-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28882536 PubMed] ISRCTN07742377
−
=Relapsed or refractory, randomized data=
+
==Doxorubicin & Ifosfamide {{#subobject:e28770|Regimen=1}}==
−
==Rituximab monotherapy {{#subobject:29dc8b|Regimen=1}}==
+
AIM: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:73277c|Variant=1}}===
+
===Regimen variant #1, 50/5000 {{#subobject:78d03a|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 584: Line 684:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/102/8/2741.long Conconi et al. 2003 (IELSG 6)]
+
|[https://doi.org/10.1200/JCO.2000.18.14.2676 Le Cesne et al. 2000 (EORTC 62903)]
−
|2000-2001
+
|1992-1995
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|style="background-color:#d3d3d3"|
+
|[[#Doxorubicin_.26_Ifosfamide|AIM]]; 75/5000
−
|style="background-color:#d3d3d3"|
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.08.128 Martinelli et al. 2005]
 
−
|NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|style="background-color:#d3d3d3"|
 
−
|style="background-color:#d3d3d3"|
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
'''28-day course'''
+
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV once on day 1
−
</div></div>
+
'''21-day cycles'''
−
===References===
+
</div></div><br>
−
# '''IELSG 6:''' Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. [http://www.bloodjournal.org/content/102/8/2741.long link to orginal article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12842999 PubMed]
 
−
# Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. [https://doi.org/10.1200/jco.2005.08.128 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15668468 PubMed]
 
−
 
 
−
=Relapsed or refractory, non-randomized or retrospective data=
 
−
==Bortezomib monotherapy {{#subobject:448e81|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 1.3 mg/m<sup>2</sup> {{#subobject:583593|Variant=1}}===
+
===Regimen variant #2, 5-day course, lower dose doxorubicin - AI 75/10,000 {{#subobject:9c1374|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 615: Line 704:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdq416 Conconi et al. 2011 (IELSG 25A)]
+
|[https://doi.org/10.1097/00000421-199806000-00025 Patel et al. 1998]
−
|2005-2009
+
|1995-1996
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#ffffbe" |Pilot, <20 patients reported
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.3 mg/m<sup>2</sup> IV once per day on days 1, 4, 8, 11
+
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 75 mg/m<sup>2</sup>)
 +
*[[Ifosfamide (Ifex)]] 2000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
====Supportive therapy====
 
====Supportive therapy====
−
*No routine growth factors, antibiotic, or antiviral prophylaxis was given
+
*[[Mesna (Mesnex)]] 400 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]], then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours
 +
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
 +
*If febrile neutropenia occurs, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] is used in subsequent cycles
 
'''21-day cycle for up to 6 cycles'''
 
'''21-day cycle for up to 6 cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 1.5 mg/m<sup>2</sup> {{#subobject:fd9bf5|Variant=1}}===
+
===Regimen variant #3, 4-day course, higher dose doxorubicin - AI 90/10,000 {{#subobject:2fd91c|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 634: Line 726:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675689/ Troch et al. 2009 (Velcade-MALT-Lymphoma)]
+
|[https://doi.org/10.1097/00000421-199806000-00025 Patel et al. 1998]
−
|NR
+
|1995-1996
−
| style="background-color:#ffffbe" |Phase 2, <20 pts
+
| style="background-color:#ffffbe" |Pilot, <20 patients reported
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Bortezomib (Velcade)]] 1.5 mg/m<sup>2</sup> IV bolus once per day on days 1, 4, 8, 11
+
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 90 mg/m<sup>2</sup>)
 +
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 4
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV immediately before [[Bortezomib (Velcade)]]
+
*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]], then 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours
−
*500 mL NS after [[Bortezomib (Velcade)]]
+
***Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
−
'''21-day cycle for up to 8 cycles'''
+
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL
 +
'''21-day cycle for up to 6 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Velcade-MALT-Lymphoma:''' Troch M, Jonak C, Müllauer L, Püspök A, Formanek M, Hauff W, Zielinski CC, Chott A, Raderer M. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009 May;94(5):738-42. Epub 2009 Mar 31. [http://www.haematologica.org/content/94/5/738.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675689/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19336742 PubMed] NCT00373906
+
# Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. [https://doi.org/10.1097/00000421-199806000-00025 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9626808 PubMed]
−
# '''IELSG 25A:''' Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJ, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E; International Extranodal Lymphoma Study Group. Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol. 2011 Mar;22(3):689-95. [https://doi.org/10.1093/annonc/mdq416 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20810546 PubMed] NCT00210327
+
# '''EORTC 62903:''' Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, Van Oosterom A, Tursz T, Verweij J. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000 Jul;18(14):2676-84. [https://doi.org/10.1200/JCO.2000.18.14.2676 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10894866 PubMed]
−
==Cladribine & Rituximab {{#subobject:bedbe7|Regimen=1}}==
+
==Doxorubicin, Ifosfamide, RT {{#subobject:e36470|Regimen=1}}==
 +
AIM & RT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:d0a8c|Variant=1}}===
+
===Regimen {{#subobject:0acb5d|Variant=1}} ===
−
{| class="wikitable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
 
!style="width: 33%"|Years of enrollment
 
!style="width: 33%"|Years of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561434/ Troch et al. 2012 (AGMT MALT)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6946838/ Spunt et al. 2019 (COG ARST0332 Arm D)]
−
|2008-2010
+
|2007-2012
−
|style="background-color:#ffffbe"|Phase 2, <20 patients reported
+
| style="background-color:#91cf61" |Phase 3b
 
|-
 
|-
 
|}
 
|}
 +
''Note: Regimen details are derived from ClinicalTrials.gov.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cladribine (Leustatin)]] 0.1 mg/kg SC once per day on days 1 to 4
+
*[[Doxorubicin (Adriamycin)]] as follows:
−
====Targeted therapy====
+
**Cycles 1 to 5: 37.5 mg/m<sup>2</sup>/day (maximum dose of 75 mg/day) IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 75 mg/m<sup>2</sup>)
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
**Doses are held when patients are receiving concurrent radiation therapy (for example, held during cycles 2 and 3, if radiation therapy is initiated with cycle 2). The missed doses are then administered in a different cycle, to maintain a total regimen dose of 375 mg/m<sup>2</sup>. If doses are held in 2 of 6 cycles, a doxorubicin-only "Cycle 7" may be given 21 days following cycle 6. 
 +
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Acetaminophen (Tylenol)]] 1000 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
+
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV over 15 minutes once per day on days 1 to 3, given 15 minutes prior to each dose of [[Ifosfamide (Ifex)]], then at 3 hours, 6 hours, and 9 hours after start of [[Ifosfamide (Ifex)]]
−
*[[:Category:Antihistamines|Antihistamine]] IV once on day 1, prior to [[Rituximab (Rituxan)]]
+
*Hydration:
−
*One of the following:
+
**Before first [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS IV at rate of 200 mL/m<sup>2</sup>/hr IV until urine output > 2 mL/kg/hr
−
**[[Ondansetron (Zofran)]] IV once per day on days 1 to 4, prior to [[Cladribine (Leustatin)]]
+
**With [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS with 10 mEq KCL/L IV at rate of 125 mL/m<sup>2</sup>/hr IV beginning immediately after ifosfamide infusion and continuing until next ifosfamide dose, or until 24 hours after last dose.
−
**[[Tropisetron (Navoban)]] IV once per day on days 1 to 4, prior to [[Cladribine (Leustatin)]]
+
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg (max 480 mcg) SC once per day, starting on day 4, given until ANC is at least 2000/uL after nadir. Filgrastim should not be administered within 24 hours of chemotherapy.
 
'''21-day cycle for up to 6 cycles'''
 
'''21-day cycle for up to 6 cycles'''
 +
====Radiotherapy====
 +
*[[External beam radiotherapy]] beginning with cycle 2 (week 4)
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
* Definitive [[Surgery#Surgical_resection|resection]] of primary tumor after recovery from cycle 3 (week 13)
 +
* Definitive [[Surgery#Surgical_resection|resection]] of residual metastasis after completion of chemotherapy
 +
</div></div>
 +
===References===
 +
<!-- # '''Abstract:''' Venkatramani R, Anderson JR, Million L, Coffin CM, McCarville B, Randall RL, et al. Risk-based treatment for synovial sarcoma in patients under 30 years of age: Children’s Oncology Group study ARST0332. J Clin Oncol [Internet]. 2015;33(15). [https://doi.org/10.1200/jco.2015.33.15_suppl.10012 link to original abstract] -->
 +
#'''COG ARST0332:''' Spunt SL, Million L, Chi YY, Anderson J, Tian J, Hibbitts E, Coffin C, McCarville MB, Randall RL, Parham DM, Black JO, Kao SC, Hayes-Jordan A, Wolden S, Laurie F, Speights R, Kawashima E, Skapek SX, Meyer W, Pappo AS, Hawkins DS. A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol. 2020 Jan;21(1):145-161. Epub 2019 Nov 27. [https://doi.org/10.1016/s1470-2045(19)30672-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6946838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31786124/ PubMed] NCT00346164
 +
==Epirubicin & Ifosfamide {{#subobject:820f20|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:55e5db|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/jco.1998.16.4.1438 Reichardt et al. 1998]
 +
|1993-1996
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Epirubicin (Ellence)]] 45 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 2 (total dose per cycle: 90 mg/m<sup>2</sup>)
 +
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 12,500 mg/m<sup>2</sup>)
 +
**Each day's dose is mixed with mesna in 3 liters of "fluids with electrolytes"
 +
====Supportive therapy====
 +
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 120 hours, started on day 1, '''given with [[Ifosfamide (Ifex)]]''' (total dose per cycle: 7500 mg/m<sup>2</sup>)
 +
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"
 +
*[[Ondansetron (Zofran)]] 8 to 24 mg/day (route not specified) prn nausea
 +
*[[Dexamethasone (Decadron)]] (dose/schedule not specified) for antiemesis if necessary
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''AGMT MALT:''' Troch M, Kiesewetter B, Willenbacher W, Willenbacher E, Zebisch A, Linkesch W, Fridrik M, Müllauer L, Greil R, Raderer M. Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie. Haematologica. 2013 Feb;98(2):264-8. Epub 2012 Sep 14. [http://www.haematologica.org/content/98/2/264.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561434/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22983582 PubMed] NCT00656812
+
# Reichardt P, Tilgner J, Hohenberger P, Dörken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. [https://doi.org/10.1200/jco.1998.16.4.1438 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9552049 PubMed]
−
==Clarithromycin monotherapy {{#subobject:bfabe7|Regimen=1}}==
+
==Gemcitabine & Vinorelbine {{#subobject:4dd538|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:a1a8c|Variant=1}}===
+
===Regimen {{#subobject:b605f7|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdv214 Ferreri et al. 2015 (HD-K)]
+
|[https://doi.org/10.1002/cncr.22609 Dileo et al. 2007]
−
|style="background-color:#91cf61"|Phase 2
+
|2003-2005
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibiotic therapy====
+
====Chemotherapy====
−
*[[Clarithromycin (Biaxin)]] 2000 mg PO once per day on days 1 to 14
+
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8
−
'''21-day cycle for 4 cycles'''
+
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 8
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''HD-K:''' Ferreri AJ, Sassone M, Kiesewetter B, Govi S, Scarfò L, Donadoni G, Raderer M. High-dose clarithromycin is an active monotherapy for patients with relapsed/refractory extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT): the HD-K phase II trial. Ann Oncol. 2015 Aug;26(8):1760-5. Epub 2015 May 1. [https://doi.org/10.1093/annonc/mdv214 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25935794 PubMed] NCT01516606
+
# Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. [https://doi.org/10.1002/cncr.22609 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17385194 PubMed]
−
==Lenalidomide monotherapy {{#subobject:2b1ccb|Regimen=1}}==
+
==MAID {{#subobject:71cfab|Regimen=1}}==
 +
MAID: '''<u>M</u>'''esna, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>I</u>'''fosfamide, '''<u>D</u>'''acarbazine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:f1de78|Variant=1}}===
+
===Regimen {{#subobject:156439|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1993.11.7.1276 Antman et al. 1993]
 +
|1987-1989
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Dacarbazine_.26_Doxorubicin|AD]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659944/ Kiesewetter et al. 2012 (LEN-MALT)]
+
|[https://doi.org/10.1007/s10637-008-9217-1 Fayette et al. 2009]
−
|style="background-color:#ffffbe"|Phase 2, <20 patients reported
+
|1994-1997
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[#MAID|MAID]; higher-intensity
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdr282 Bui-Nguyen et al. 2011]
 +
|2000-2008
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>In Antman et al. 1993, although this arm seemed to have superior TTP, the control arm seemed to have superior OS.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
+
*[[Doxorubicin (Adriamycin)]]
 +
*[[Ifosfamide (Ifex)]]
 +
*[[Dacarbazine (DTIC)]]
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Aspirin]] 100 mg PO once per day
+
*[[Mesna (Mesnex)]]
−
'''28-day cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LEN-MALT:''' Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M. A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma). Haematologica. 2013 Mar;98(3):353-6. Epub 2012 Aug 16. [http://www.haematologica.org/content/98/3/353.long link to orginal article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659944/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22899582 PubMed] NCT00923663
+
# Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, Doroshow JH, Aisner J, Pugh RP, Weiss RB, Cooper BA, Clamond GH, Baker LH. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. [https://doi.org/10.1200/JCO.1993.11.7.1276 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8315425 PubMed]
−
=Prognosis=
+
# Fayette J, Penel N, Chevreau C, Blay JY, Cupissol D, Thyss A, Guillemet C, Rios M, Rolland F, Fargeot P, Bay JO, Mathoulin-Pelissier S, Coindre JM, Bui-Nguyen B. Phase III trial of standard versus dose-intensified doxorubicin, ifosfamide and dacarbazine (MAID) in the first-line treatment of metastatic and locally advanced soft tissue sarcoma. Invest New Drugs. 2009 Oct;27(5):482-9. Epub 2009 Jan 16. [https://doi.org/10.1007/s10637-008-9217-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19148579 PubMed]
−
==MALT-IPI (2017)==
+
# Bui-Nguyen B, Ray-Coquard I, Chevreau C, Penel N, Bay JO, Coindre JM, Cupissol D, Italiano A, Bonichon F, Lotz JP, Thyss A, Jimenez M, Mathoulin-Pélissier S, Blay JY; GSF-GETO. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial. Ann Oncol. 2012 Mar;23(3):777-84. Epub 2011 Jun 7. [https://doi.org/10.1093/annonc/mdr282 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21652583 PubMed]
−
===Risk factors===
+
=Dermatofibrosarcoma protuberans, all lines of therapy=
−
*Stage III or IV
+
==Imatinib monotherapy {{#subobject:d700c4|Regimen=1}}==
−
*Age older than 70 years
+
<div class="toccolours" style="background-color:#eeeeee">
−
*LDH greater than the upper limit of normal
+
===Regimen variant #1, 400 mg/day {{#subobject:966ba9|Variant=1}}===
−
===Calculation===
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
*'''Low risk:''' zero risk factors present
+
!style="width: 33%"|Study
−
*'''Intermediate risk:''' one risk factor present
+
!style="width: 33%"|Years of enrollment
−
*'''High risk:''' two or more risk factors present
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040044/ Rutkowski et al. 2010 (SWOG S0345)]
 +
|2005-2006
 +
| style="background-color:#ffffbe" |Phase 2, <20 pts
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Imatinib (Gleevec)]] 400 mg PO once per day
 +
'''48-week course'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 800 mg/day {{#subobject:7389b7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040044/ Rutkowski et al. 2010 (EORTC 62027)]
 +
|2004-2007
 +
| style="background-color:#ffffbe" |Phase 2, <20 pts (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Imatinib (Gleevec)]] 400 mg PO twice per day
 +
'''Continued indefinitely, unless complete (R0) surgical resection became possible'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Thieblemont C, Cascione L, Conconi A, Kiesewetter B, Raderer M, Gaidano G, Martelli M, Laszlo D, Coiffier B, Lopez Guillermo A, Torri V, Cavalli F, Johnson PW, Zucca E. A MALT lymphoma prognostic index. Blood. 2017 Sep 21;130(12):1409-1417. Epub 2017 Jul 18. [http://www.bloodjournal.org/content/130/12/1409.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/28720586 PubMed]
+
# '''EORTC 62027:''' Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; [[Study_Groups#SWOG|SWOG]]. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010 Apr 1;28(10):1772-9. Epub 2010 Mar 1. [https://doi.org/10.1200/JCO.2009.25.7899 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20194851 PubMed] NCT00085475
−
=Response criteria=
+
# '''SWOG S0345:''' Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; [[Study_Groups#EORTC|EORTC]] Soft Tissue and Bone Sarcoma Group; [[Study_Groups#SWOG|SWOG]]. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010 Apr 1;28(10):1772-9. Epub 2010 Mar 1. [https://doi.org/10.1200/JCO.2009.25.7899 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20194851 PubMed] NCT00084630
−
==NCI Sponsored International Working Group Criteria (1999)==
+
[[Category:Soft tissue sarcoma regimens]]
−
# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [https://doi.org/10.1200/jco.1999.17.4.1244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561185 PubMed]
 
−
[[Category:MALT lymphoma regimens]]
 
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Marginal zone lymphomas]]
+
[[Category:Soft tissue sarcomas]]
−
[[Category:Non-Hodgkin lymphomas]]
 

Revision as of 01:46, 15 October 2022

Back to Top

Section editor transclusions

0 regimens on this page
0 variants on this page

Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
Note: this page is for subtype-nonspecific soft tissue sarcoma regimens, some subtypes with very few subtype-specific regimens, as well as for sarcomas that are not readily categorized, e.g., alveolar soft part sarcoma. Please see the category page for links to other sarcoma types or use one of these links:


Guidelines

ESMO/EURACAN/GENTURIS

Older

NCCN

Neoadjuvant therapy

Epirubicin & Ifosfamide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gronchi et al. 2012 2002-2007 Non-randomized portion of phase 3 RCT
Gronchi et al. 2017 (ISG-STS 1001) 2011-2016 Phase 3 (C) Histotype-tailored therapy Did not meet primary endpoint of DFS1

1Reported efficacy for ISG-STS 1001 is based on the 2020 update.

Chemotherapy

Supportive therapy

  • Mesna (Mesnex) 1000 mg/m2 IV every 3 hours to every 4 hours on days 1 to 3

21-day cycle for 3 cycles

Subsequent treatment

References

  1. Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, Mariani L, Valagussa P, Miceli R, Stacchiotti S, Dei Tos AP, De Paoli A, Longhi A, Poveda A, Quagliuolo V, Comandone A, Casali PG, Picci P; Italian Sarcoma Group; Spanish Sarcoma Group. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012 Mar 10;30(8):850-6. Epub 2012 Feb 6. link to original article contains dosing details in manuscript PubMed EudraCT 2004-003979-36
  2. ISG-STS 1001: Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. link to original article contains dosing details in abstract PubMed NCT01710176
    1. Update: Gronchi A, Palmerini E, Quagliuolo V, Martin Broto J, Lopez Pousa A, Grignani G, Brunello A, Blay JY, Tendero O, Diaz Beveridge R, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Braglia L, Donati DM, Palassini E, Bianchi G, Marrari A, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups. J Clin Oncol. 2020 Jul 1;38(19):2178-2186. Epub 2020 May 18. link to original article PubMed

EIA

EIA: Etoposide, Ifosfamide, Adriamycin (Doxorubicin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Issels et al. 2010 (EORTC 62961/ESHO 95) 1997-2006 Phase 3 (C) EIA & regional hyperthermia Seems to have inferior OS

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

References

  1. EORTC 62961/ESHO 95: Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. Epub 2010 Apr 29. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00003052
    1. Update: Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):483-492. link to original article link to PMC article PubMed

Adjuvant therapy

EIA

EIA: Etoposide, Ifosfamide, Adriamycin (Doxorubicin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Issels et al. 2010 (EORTC 62961/ESHO 95) 1997-2006 Phase 3 (C) EIA & regional hyperthermia Seems to have inferior OS

Preceding treatment

  • Neoadjuvant EIA x 4, then surgery, then adjuvant RT

Chemotherapy

21-day cycle for 4 cycles

References

  1. EORTC 62961/ESHO 95: Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, Abdel-Rahman S, Daugaard S, Salat C, Wendtner CM, Vujaskovic Z, Wessalowski R, Jauch KW, Dürr HR, Ploner F, Baur-Melnyk A, Mansmann U, Hiddemann W, Blay JY, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study. Lancet Oncol. 2010 Jun;11(6):561-70. Epub 2010 Apr 29. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00003052
    1. Update: Issels RD, Lindner LH, Verweij J, Wessalowski R, Reichardt P, Wust P, Ghadjar P, Hohenberger P, Angele M, Salat C, Vujaskovic Z, Daugaard S, Mella O, Mansmann U, Dürr HR, Knösel T, Abdel-Rahman S, Schmidt M, Hiddemann W, Jauch KW, Belka C, Gronchi A; European Organization for the Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group; European Society for Hyperthermic Oncology. Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: the EORTC 62961-ESHO 95 randomized clinical trial. JAMA Oncol. 2018 Apr 1;4(4):483-492. link to original article link to PMC article PubMed

Locally advanced or metastatic disease, single-agent regimens

Cisplatin monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Blay et al. 2015 (EFC10145) 2008-2012 Phase 3 (C) Cisplatin & Ombrabulin Seems to have inferior PFS

Note: PFS was very poor in both groups (less than 2 months); the difference was not considered clinically meaningful.

Chemotherapy

21-day cycles

References

  1. EFC10145: Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. Epub 2015 Apr 8. link to original article contains dosing details in abstract PubMed NCT00699517

Dacarbazine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Buesa et al. 1991 1984-1986 Phase 2
García-Del-Muro et al. 2011 2005-2008 Randomized Phase 2 (C) Dacarbazine & Gemcitabine Seems to have inferior OS

Chemotherapy

Supportive therapy

  • Buesa et al. 1991: Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.

21-day cycles

References

  1. Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R; EORTC Soft Tissue and Bone Sarcoma Group. High-dose DTIC in advanced soft-tissue sarcomas in the adult: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. link to original article contains dosing details in manuscript PubMed
  2. García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. link to original article contains dosing details in manuscript PubMed EudraCT 2005-001709-24

Doxorubicin monotherapy

Regimen variant #1, 75 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cruz et al. 1979 (COG 7231A) NR Phase 3 (E-switch-ic) 1. Actinomycin & Melphalan
2. Melphalan & Vincristine
3. Melphalan & NSC-1026 		Superior ORR
Mouridsen et al. 1987 (EORTC 62801) 1980-1983 Phase 3 (E-switch-ic) Epirubicin Did not meet primary endpoint of ORR
Santoro et al. 1995 1985-1990 Phase 3 (C) 1. Doxorubicin & Ifosfamide
2. CYVADIC 		Did not meet endpoints of ORR/DOR/OS
Nielsen et al. 1998 NR Phase 3 (C) Epirubicin Did not meet primary endpoint of ORR
Lorigan et al. 2007 (EORTC 62971) 1998-2001 Phase 3 (C) 1. Ifos 3 Did not meet primary endpoint of PFS
2. Ifos 9 Did not meet primary endpoint of PFS
Judson et al. 2014 (EORTC 62012) 2003-2010 Phase 3 (C) Doxorubicin & Ifosfamide; intensified Might have inferior OS
Blay et al. 2014 (CR015769) 2008-2012 Phase 3 (C) Trabectedin Did not meet primary endpoint of PFS
Ryan et al. 2016 (PICASSO III) 2010-2012 Phase 3 (C) Doxorubicin & Palifosfamide Did not meet primary endpoint of PFS
Tap et al. 2016 (CP15-0806) 2010-2013 Randomized Phase 2 (C) Doxorubicin & Olaratumab Inferior OS
Seddon et al. 2017 (GeDDiS) 2010-2014 Phase 3 (C) Docetaxel & Gemcitabine Might have superior PFS
Tap et al. 2017 (TH CR-406/SARC021) 2011-2014 Phase 3 (C) Doxorubicin & Evofosfamide Did not meet primary endpoint of OS
Tap et al. 2020 (ANNOUNCE) 2015-2018 Phase 3 (C) Doxorubicin & Olaratumab Did not meet primary endpoint of OS

Note: in EORTC 62801, treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m2, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician. Patients in CR015769 had translocation-related sarcomas.

Chemotherapy

Supportive therapy

21-day cycle for up to 6 to 8 cycles (see note)


Regimen variant #2, 80 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Edmonson et al. 1993 1987-1990 Phase 3 (C) 1. Doxorubicin & Ifosfamide Seems to have inferior ORR
2. MAC Might have inferior ORR

Chemotherapy

21-day cycles

References

  1. COG 7231-A: Cruz AB Jr, Thames EA Jr, Aust JB, Metter G, Ramirez G, Fletcher WS, Altman SJ, Frelick RW, Hill GJ 2nd. Combination chemotherapy for soft-tissue sarcomas: a phase III study. J Surg Oncol. 1979;11(4):313-23. link to original article PubMed
  2. EORTC 62801: Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R; EORTC Soft Tissue and Bone Sarcoma Group. Adriamycin versus epirubicin in advanced soft tissue sarcomas: a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. link to original article contains dosing details in manuscript PubMed
  3. Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269-75. link to original article contains dosing details in abstract PubMed
  4. Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa J, Casali P, Spooner D, Rankin E, Kirkpatrick A, van Glabbeke M, van Oosterom A; EORTC Soft Tissue and Bone Sarcoma Group. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537-45. link to original article PubMed
  5. Nielsen OS, Dombernowsky P, Mouridsen H, Crowther D, Verweij J, Buesa J, Steward W, Daugaard S, van Glabbeke M, Kirkpatrick A, Tursz T; EORTC soft tissue and bone sarcoma group. High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas: a study of the EORTC soft tissue and bone sarcoma group. Br J Cancer. 1998 Dec;78(12):1634-9. linkt o original article link to PMC article PubMed
  6. Meta-analysis: Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. link to original article link to PMC article PubMed
  7. EORTC 62971: Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; EORTC Soft Tissue and Bone Sarcoma Group. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. link to original article contains dosing details in manuscript PubMed NCT00003212
  8. CR015769: Blay JY, Leahy MG, Nguyen BB, Patel SR, Hohenberger P, Santoro A, Staddon AP, Penel N, Piperno-Neumann S, Hendifar A, Lardelli P, Nieto A, Alfaro V, Chawla SP. Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas. Eur J Cancer. 2014 Apr;50(6):1137-47. Epub 2014 Feb 7. link to original article contains dosing details in abstract PubMed NCT00796120
  9. EORTC 62012: Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. link to original article PubMed NCT00061984
  10. CP15-0806: Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01185964
  11. PICASSO III: Ryan CW, Merimsky O, Agulnik M, Blay JY, Schuetze SM, Van Tine BA, Jones RL, Elias AD, Choy E, Alcindor T, Keedy VL, Reed DR, Taub RN, Italiano A, Garcia Del Muro X, Judson IR, Buck JY, Lebel F, Lewis JJ, Maki RG, Schöffski P. PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma. J Clin Oncol. 2016 Nov 10;34(32):3898-3905. Epub 2016 Sep 30. link to original article PubMed NCT01168791
  12. TH CR-406/SARC021: Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. Epub 2017 Jun 23. link to original article contains dosing details in abstract PubMed NCT01440088
  13. GeDDiS: Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. link to original article link to PMC article contains dosing details in manuscript PubMed ISRCTN07742377
  14. ANNOUNCE: Tap WD, Wagner AJ, Schöffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, Yen CC, Abdul Razak AR, Spira A, Kawai A, Le Cesne A, Van Tine BA, Naito Y, Park SH, Fedenko A, Pápai Z, Soldatenkova V, Shahir A, Mo G, Wright J, Jones RL; ANNOUNCE Investigators. Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial. JAMA. 2020 Apr 7;323(13):1266-1276. link to original article link to PMC article PubMed NCT02451943

Epirubicin monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Mouridsen et al. 1987 (EORTC 62801) 1980-1983 Phase 3 (E-switch-ic) Doxorubicin Did not meet primary endpoint of ORR

Chemotherapy

21-day cycle for up to 7 cycles (cumulative epirubicin dosage of 550 mg/m2) (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)

References

  1. EORTC 62801: Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D, Sylvester R. Adriamycin versus epirubicin in advanced soft tissue sarcomas: a randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. link to original article contains dosing details in manuscript PubMed

Ifosfamide monotherapy

Regimen variant #1, short infusion (Ifos 3)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lorigan et al. 2007 (EORTC 62971) 1998-2001 Phase 3 (E-switch-ic) 1. Doxorubicin Did not meet primary endpoint of PFS
2. Ifosfamide; Ifos 9 Did not meet primary endpoint of PFS

Chemotherapy

  • Ifosfamide (Ifex) 3000 mg/m2 IV over 4 hours on days 1 to 3, mixed with mesna in 1 liter of normal saline

Supportive therapy

  • Mesna (Mesnex) 600 mg/m2 IV bolus once on day 1, given immediately prior to mesna/ifosfamide infusion, then 1500 mg/m2 IV over 4 hours on days 1 to 3, given with Ifosfamide (Ifex), then 1200 mg/m2 IV twice per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna
    • An alternative is to use oral mesna instead of intravenous: Mesna (Mesnex) 1200 mg/m2 PO twice per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna
  • Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
  • Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion

21-day cycle for up to 6 cycles


Regimen variant #2, continuous infusion (Ifos 9)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lorigan et al. 2007 (EORTC 62971) 1998-2001 Phase 3 (E-esc) 1. Doxorubicin Did not meet primary endpoint of PFS
2. Ifosfamide; Ifos 3 Did not meet primary endpoint of PFS

Chemotherapy

  • Ifosfamide (Ifex) 3000 mg/m2/day IV continuous infusion over 72 hours, started on day 1, given with mesna (total dose per cycle: 9000 mg/m2)
    • Each day's dose is mixed with mesna in 3 liters of normal saline

Supportive therapy

  • Mesna (Mesnex) 600 mg/m2 IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then 3000 mg/m2/day IV continuous infusion over 72 hours, starting on day 1, given with Ifosfamide (Ifex), then 1800 mg/m2 IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna
    • An alternative is to use oral mesna instead of intravenous: Mesna (Mesnex) 1200 mg/m2 PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna
  • Sodium bicarbonate 150 mmol IV once per day on days 1 to 3
  • Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion

21-day cycle for up to 6 cycles


Regimen variant #3

Study Years of enrollment Evidence
van Oosterom et al. 2002 1992-1994 Phase 2

Chemotherapy

  • Ifosfamide (Ifex) 3000 mg/m2 IV over 4 hours once per day on days 1 to 3, dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed with mesna in an additional 1 liter of dextrose/saline

Supportive therapy

  • Mesna (Mesnex) 600 mg/m2 IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then 1500 mg/m2 IV over 4 hours on days 1 to 3, given with Ifosfamide (Ifex), then 500 mg/m2 IV twice per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna
  • "Antiemetics were prescribed according to local conventions"
  • 1 liter of fluid PO twice per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna

21-day cycle for at least 2 cycles, except in cases of rapid disease progression

References

  1. van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
  2. EORTC 62971: Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; EORTC Soft Tissue and Bone Sarcoma Group. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. link to original article contains dosing details in manuscript PubMed NCT00003212

Pazopanib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
van der Graaf et al. 2012 (PALETTE) 2008-2010 Phase 3 (E-RT-esc) Placebo Superior PFS
Median PFS: 4.6 vs 1.6 mo
(HR 0.31, 95% CI 0.24-0.40)

Targeted therapy

Continued indefinitely

References

  1. PALETTE: van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. link to original article contains dosing details in manuscript PubMed NCT00753688
    1. Subgroup analysis: Kawai A, Araki N, Hiraga H, Sugiura H, Matsumine A, Ozaki T, Ueda T, Ishii T, Esaki T, Machida M, Fukasawa N. A randomized, double-blind, placebo-controlled, phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup. Jpn J Clin Oncol. 2016 Mar;46(3):248-53. Epub 2016 Feb 10. link to original article link to PMC article PubMed

Regorafenib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Mir et al. 2016 (REGOSARC) 2013-2014 Randomized Phase 2 (E-esc) Placebo Superior PFS

Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.

Targeted therapy

28-day cycles

References

  1. REGOSARC: Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. link to original article contains dosing details in abstract PubMed NCT01900743

Temozolomide monotherapy

Regimen variant #1, 5 out of 28 days

Study Years of enrollment Evidence
Talbot et al. 2003 1998-2000 Phase 2

Note: patients on study could be reconsented to receive therapy beyond 1 year. Treatment given on an empty stomach, and doses rounded up if needed to next available dosage based on capsule doses.

Chemotherapy

  • Temozolomide (Temodar) 200 mg/m2 PO once on day 1, then 12 hours later, 90 mg/m2 PO every 12 hours on days 1 to 5 (total of 10 doses per cycle)

Supportive therapy

  • Antiemetics "prescribed as clinically indicated by the treating physician"

28-day cycle for up to 13 cycles (1 year)


Regimen variant #2, 6 out of 9 weeks

Study Years of enrollment Evidence
Garcia del Muro et al. 2005 1999-2001 Phase 2

Note: Initial dose used in the study was 75 mg/m2, but due to lack of toxicity, protocol was amended to use 100 mg/m2 doses.

Chemotherapy

  • Temozolomide (Temodar) 100 mg/m2 PO once per day on days 1 to 42, no food 1 hour before and after temozolomide doses

Supportive therapy

9-week cycle for up to 3 cycles

References

  1. Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. link to original article contains dosing details in manuscript PubMed
  2. Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. link to original article contains dosing details in manuscript PubMed

Trabectedin monotherapy

Regimen #1, 1.2 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kawai et al. 2015 2012-2014 Randomized Phase 2 (E-esc) Placebo Superior PFS

Chemotherapy

21-day cycles

Regimen #2, 1.5 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Le Cesne et al. 2021 (T-SAR) 2015 Phase 3 (E-esc) Best supportive care Superior PFS
Median PFS: 3.1 vs 1.5 mo
(HR 0.39, 95% CI 0.24-0.64)

Chemotherapy

21-day cycles

References

  1. Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. link to original article contains dosing details in abstract PubMed JapicCTI-121850
  2. T-SAR: Le Cesne A, Blay JY, Cupissol D, Italiano A, Delcambre C, Penel N, Isambert N, Chevreau C, Bompas E, Bertucci F, Chaigneau L, Piperno-Neumann S, Salas S, Rios M, Guillemet C, Bay JO, Ray-Coquard I, Haddag L, Bonastre J, Kapso R, Fraslin A, Bouvet N, Mir O, Foulon S. A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial. Ann Oncol. 2021 Aug;32(8):1034-1044. Epub 2021 Apr 29. link to original article contains dosing details in manuscript PubMed NCT02672527

Locally advanced or metastatic disease, combination regimens

Dacarbazine & Doxorubicin

AD: Adriamycin (Doxorubicin) & Dacarbazine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Baker et al. 1987 (SWOG S7613) 1976-1979 Phase 3 (C) 1. AD & Cyclophosphamide
2. AD & Dactinomycin 		Did not meet endpoints of RR/OS
Zalupski et al. 1991 1980-1986 Phase 3 (C) Dacarbazine & Doxorubicin; CI Did not meet primary endpoint of OS50%
Antman et al. 1993 1987-1989 Phase 3 (C) MAID Seems to have superior OS1

1In Antman et al. 1993, although the experimental arm seemed to have superior TTP, this arm seemed to have superior OS.
Here for historic purposes.

Chemotherapy

21-day cycles

References

  1. SWOG S7613: Baker LH, Frank J, Fine G, Balcerzak SP, Stephens RL, Stuckey WJ, Rivkin S, Saiki J, Ward JH. Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial: a phase III, Southwest Oncology Group Study (7613). J Clin Oncol. 1987 Jun;5(6):851-61. link to original article PubMed
  2. Zalupski M, Metch B, Balcerzak S, Fletcher WS, Chapman R, Bonnet JD, Weiss GR, Ryan J, Benjamin RS, Baker LH; SWOG. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Jul 3;83(13):926-32. link to original article contains dosing details in abstract PubMed
  3. Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, Doroshow JH, Aisner J, Pugh RP, Weiss RB, Cooper BA, Clamond GH, Baker LH. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. link to original article PubMed

Dacarbazine & Gemcitabine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
García-Del-Muro et al. 2011 2005-2008 Randomized Phase 2, <20 pts in this subgroup (E-esc) Dacarbazine Seems to have superior OS

Chemotherapy

14-day cycle for at least 12 cycles

References

  1. García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. link to original article contains dosing details in manuscript PubMed EudraCT 2005-001709-24

Docetaxel & Gemcitabine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Seddon et al. 2017 (GeDDiS) 2010-2014 Phase 3 (E-switch-ic) Doxorubicin Might have inferior PFS

Chemotherapy

Supportive therapy

  • Dexamethasone (Decadron) 8 mg PO twice per day on days 7 to 9 (the day before, the day of, and day after Docetaxel (Taxotere))
  • Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel
  • One of the following growth factors (varies depending on reference):
    • G-CSF (type not specified) 150 mcg/m2 (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements
    • Pegfilgrastim (Neulasta) 6 mg SC once on either day 9 or 10

21-day cycle for 6 to 8 cycles

References

  1. GeDDiS: Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. link to original article link to PMC article PubMed ISRCTN07742377

Doxorubicin & Ifosfamide

AIM: Adriamycin (Doxorubicin), Ifosfamide, Mesna

Regimen variant #1, 50/5000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Le Cesne et al. 2000 (EORTC 62903) 1992-1995 Phase 3 (C) AIM; 75/5000 Did not meet primary endpoint of ORR

Chemotherapy

21-day cycles


Regimen variant #2, 5-day course, lower dose doxorubicin - AI 75/10,000

Study Years of enrollment Evidence
Patel et al. 1998 1995-1996 Pilot, <20 patients reported

Chemotherapy

Supportive therapy

  • Mesna (Mesnex) 400 mg/m2 IV once on day 1, given simultaneously with the first dose of Ifosfamide (Ifex), then 1200 mg/m2/day IV continuous infusion over 120 hours
    • Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
  • If febrile neutropenia occurs, G-CSF is used in subsequent cycles

21-day cycle for up to 6 cycles


Regimen variant #3, 4-day course, higher dose doxorubicin - AI 90/10,000

Study Years of enrollment Evidence
Patel et al. 1998 1995-1996 Pilot, <20 patients reported

Chemotherapy

Supportive therapy

  • Mesna (Mesnex) 500 mg/m2 IV once on day 1, given simultaneously with the first dose of Ifosfamide (Ifex), then 1500 mg/m2/day IV continuous infusion over 96 hours
      • Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate
  • G-CSF (type not specified) 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL

21-day cycle for up to 6 cycles

References

  1. Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. link to original article contains dosing details in manuscript PubMed
  2. EORTC 62903: Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, Van Oosterom A, Tursz T, Verweij J. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000 Jul;18(14):2676-84. link to original article contains dosing details in abstract PubMed

Doxorubicin, Ifosfamide, RT

AIM & RT: Adriamycin (Doxorubicin), Ifosfamide, Mesna, Radiation Therapy

Regimen

Study Years of enrollment Evidence
Spunt et al. 2019 (COG ARST0332 Arm D) 2007-2012 Phase 3b

Note: Regimen details are derived from ClinicalTrials.gov.

Chemotherapy

  • Doxorubicin (Adriamycin) as follows:
    • Cycles 1 to 5: 37.5 mg/m2/day (maximum dose of 75 mg/day) IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 75 mg/m2)
    • Doses are held when patients are receiving concurrent radiation therapy (for example, held during cycles 2 and 3, if radiation therapy is initiated with cycle 2). The missed doses are then administered in a different cycle, to maintain a total regimen dose of 375 mg/m2. If doses are held in 2 of 6 cycles, a doxorubicin-only "Cycle 7" may be given 21 days following cycle 6.
  • Ifosfamide (Ifex) 3000 mg/m2 IV over 3 hours once per day on days 1 to 3

Supportive therapy

  • Mesna (Mesnex) 600 mg/m2 IV over 15 minutes once per day on days 1 to 3, given 15 minutes prior to each dose of Ifosfamide (Ifex), then at 3 hours, 6 hours, and 9 hours after start of Ifosfamide (Ifex)
  • Hydration:
    • Before first Ifosfamide (Ifex) infusion: D5 1/2 NS IV at rate of 200 mL/m2/hr IV until urine output > 2 mL/kg/hr
    • With Ifosfamide (Ifex) infusion: D5 1/2 NS with 10 mEq KCL/L IV at rate of 125 mL/m2/hr IV beginning immediately after ifosfamide infusion and continuing until next ifosfamide dose, or until 24 hours after last dose.
  • G-CSF (type not specified) 5 mcg/kg (max 480 mcg) SC once per day, starting on day 4, given until ANC is at least 2000/uL after nadir. Filgrastim should not be administered within 24 hours of chemotherapy.

21-day cycle for up to 6 cycles

Radiotherapy

Subsequent treatment

  • Definitive resection of primary tumor after recovery from cycle 3 (week 13)
  • Definitive resection of residual metastasis after completion of chemotherapy

References

  1. COG ARST0332: Spunt SL, Million L, Chi YY, Anderson J, Tian J, Hibbitts E, Coffin C, McCarville MB, Randall RL, Parham DM, Black JO, Kao SC, Hayes-Jordan A, Wolden S, Laurie F, Speights R, Kawashima E, Skapek SX, Meyer W, Pappo AS, Hawkins DS. A risk-based treatment strategy for non-rhabdomyosarcoma soft-tissue sarcomas in patients younger than 30 years (ARST0332): a Children's Oncology Group prospective study. Lancet Oncol. 2020 Jan;21(1):145-161. Epub 2019 Nov 27. link to original article link to PMC article PubMed NCT00346164

Epirubicin & Ifosfamide

Regimen

Study Years of enrollment Evidence
Reichardt et al. 1998 1993-1996 Phase 2

Chemotherapy

  • Epirubicin (Ellence) 45 mg/m2/day IV continuous infusion over 48 hours, started on day 2 (total dose per cycle: 90 mg/m2)
  • Ifosfamide (Ifex) 2500 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 12,500 mg/m2)
    • Each day's dose is mixed with mesna in 3 liters of "fluids with electrolytes"

Supportive therapy

  • Mesna (Mesnex) 1500 mg/m2 IV continuous infusion over 120 hours, started on day 1, given with Ifosfamide (Ifex) (total dose per cycle: 7500 mg/m2)
  • G-CSF (type not specified) 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"
  • Ondansetron (Zofran) 8 to 24 mg/day (route not specified) prn nausea
  • Dexamethasone (Decadron) (dose/schedule not specified) for antiemesis if necessary

21-day cycles

References

  1. Reichardt P, Tilgner J, Hohenberger P, Dörken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. link to original article contains dosing details in manuscript PubMed

Gemcitabine & Vinorelbine

Regimen

Study Years of enrollment Evidence
Dileo et al. 2007 2003-2005 Phase 2

Chemotherapy

21-day cycles

References

  1. Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. link to original article contains dosing details in manuscript PubMed

MAID

MAID: Mesna, Adriamycin (Doxorubicin), Ifosfamide, Dacarbazine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Antman et al. 1993 1987-1989 Phase 3 (E-esc) AD Seems to have inferior OS1
Fayette et al. 2009 1994-1997 Phase 3 (C) MAID]; higher-intensity Did not meet primary endpoint of ORR
Bui-Nguyen et al. 2011 2000-2008 Non-randomized portion of phase 3 RCT

1In Antman et al. 1993, although this arm seemed to have superior TTP, the control arm seemed to have superior OS.

Chemotherapy

Supportive therapy

References

  1. Antman K, Crowley J, Balcerzak SP, Rivkin SE, Weiss GR, Elias A, Natale RB, Cooper RM, Barlogie B, Trump DL, Doroshow JH, Aisner J, Pugh RP, Weiss RB, Cooper BA, Clamond GH, Baker LH. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993 Jul;11(7):1276-85. link to original article PubMed
  2. Fayette J, Penel N, Chevreau C, Blay JY, Cupissol D, Thyss A, Guillemet C, Rios M, Rolland F, Fargeot P, Bay JO, Mathoulin-Pelissier S, Coindre JM, Bui-Nguyen B. Phase III trial of standard versus dose-intensified doxorubicin, ifosfamide and dacarbazine (MAID) in the first-line treatment of metastatic and locally advanced soft tissue sarcoma. Invest New Drugs. 2009 Oct;27(5):482-9. Epub 2009 Jan 16. link to original article PubMed
  3. Bui-Nguyen B, Ray-Coquard I, Chevreau C, Penel N, Bay JO, Coindre JM, Cupissol D, Italiano A, Bonichon F, Lotz JP, Thyss A, Jimenez M, Mathoulin-Pélissier S, Blay JY; GSF-GETO. High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial. Ann Oncol. 2012 Mar;23(3):777-84. Epub 2011 Jun 7. link to original article PubMed

Dermatofibrosarcoma protuberans, all lines of therapy

Imatinib monotherapy

Regimen variant #1, 400 mg/day

Study Years of enrollment Evidence
Rutkowski et al. 2010 (SWOG S0345) 2005-2006 Phase 2, <20 pts

Targeted therapy

48-week course


Regimen variant #2, 800 mg/day

Study Years of enrollment Evidence
Rutkowski et al. 2010 (EORTC 62027) 2004-2007 Phase 2, <20 pts (RT)

Targeted therapy

Continued indefinitely, unless complete (R0) surgical resection became possible

References

  1. EORTC 62027: Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; EORTC Soft Tissue and Bone Sarcoma Group; SWOG. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010 Apr 1;28(10):1772-9. Epub 2010 Mar 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00085475
  2. SWOG S0345: Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, Lazar A, Gelderblom H, Sciot R, Lopez-Terrada D, Hohenberger P, van Oosterom AT, Schuetze SM; EORTC Soft Tissue and Bone Sarcoma Group; SWOG. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol. 2010 Apr 1;28(10):1772-9. Epub 2010 Mar 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00084630
Retrieved from "https://hemonc.org/w/index.php?title=Staging_page&oldid=63161"