Difference between revisions of "Staging page"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
m
Line 4: Line 4:
 
</div>
 
</div>
 
{{#lst:Section editor transclusions|tcl}}
 
{{#lst:Section editor transclusions|tcl}}
−
<big>'''Note: these studies were specific to ALCL or had ALCL subgroups; regimens used in [[Peripheral_T-cell_lymphoma|PTCL, NOS]] are also often used in this condition. Certain regimens have been moved to dedicated pages:
 
−
*'''[[Anaplastic large cell lymphoma, pediatric|Pediatric ALCL]]
 
−
</big>
 
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
Line 13: Line 10:
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 +
''Note: a variant of this disease, aggressive NK-cell leukemia, is usually considered a separate entity (somewhat analogous to [[plasma cell leukemia]] and [[multiple myeloma]]). There are no prospective trials reported for this variant.''
 
=Guidelines=
 
=Guidelines=
 
==[http://www.esmo.org/ ESMO]==
 
==[http://www.esmo.org/ ESMO]==
 
*'''2015:''' d'Amore et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Peripheral-T-Cell-Lymphomas Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
*'''2015:''' d'Amore et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Peripheral-T-Cell-Lymphomas Peripheral T-cell lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 +
=="How I Treat"==
 +
*'''2013:''' Tse E, Kwong YL. How I treat NK/T-cell lymphomas. Blood. 2013 Jun 20;121(25):4997-5005. Epub 2013 May 7. [http://www.bloodjournal.org/content/121/25/4997.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23652805 PubMed]
 +
==[https://www.nccn.org/ NCCN]==
 +
*[https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf NCCN Guidelines - T-cell Lymphomas]
 
=Untreated=
 
=Untreated=
−
==BV-CHP {{#subobject:6964de|Regimen=1}}==
+
==DDGP {{#subobject:abc3fd|Regimen=1}}==
−
BV-CHP: '''<u>B</u>'''rentuximab '''<u>V</u>'''edotin, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>P</u>'''rednisone
+
DDGP: '''<u>D</u>'''examethasone, '''<u>D</u>'''DP (Cisplatin), '''<u>G</u>'''emcitabine, '''<u>P</u>'''egaspargase
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:985a91|Variant=1}}===
+
===Regimen {{#subobject:d2e0fd|Variant=1}}===
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
 
{| 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 32: Line 30:
 
!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/PMC6436818/ Horwitz et al. 2018 (ECHELON-2)]
+
|[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)]
−
|2013-2016
+
|2011-2014
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
+
|style="background-color:#1a9851"|Phase 4 (E-switch-ic)
−
|[[#CHOP|CHOP]]
+
|[[#SMILE|SMILE]]
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: NYR vs NYR<br>(HR 0.66, 95% CI 0.46-0.95)
+
|style="background-color:#91cf60"|Seems to have superior OS<br>OS24: 74% vs 45%
 
|-
 
|-
 
|}
 
|}
 +
''Note: dosing information is from the [https://clinicaltrials.gov/show/NCT01501149 NCT record].''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibody-drug conjugate therapy====
 
−
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+
*[[Dexamethasone (Decadron)]] 15 mg/m<sup>2</sup> IV once per day on days 1 to 5
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''ECHELON-2:''' Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trümper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. Epub 2018 Dec 4. Erratum in: Lancet. 2019 Jan 19;393(10168):228. [https://doi.org/10.1016/S0140-6736(18)32984-2 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436818/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30522922 PubMed] NCT01777152
 
−
==CHOEP-14 {{#subobject:c516ab|Regimen=1}}==
 
−
CHOEP-14: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone every '''<u>14</u>''' days
 
−
<br>CHOPE
 
−
<br>VACOP
 
−
===Example orders===
 
−
*[[Example orders for CHOEP in lymphoma]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f61648|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this subgroup (E-esc)
 
−
|1. [[#CHOEP-21|CHOEP-21]]<br>2. [[#CHOP|CHOP-21]]<br> 3. [[#CHOP-14_99|CHOP-14]]
 
−
|Not reported by subgroup
 
−
|Not reported by subgroup
 
−
|}
 
−
''This regimen was used in 16 ALCL patients in the NHL-B1 trial. The authors did not report a subgroup analysis for this minority population.''
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
+
*[[Pegaspargase (Oncaspar)]] 2500 IU/m<sup>2</sup> IM once on day 1
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
'''21-day cycle for at least 3 cycles'''
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] by the following criteria:
 
−
**Patients less than 75 kg: 300 mcg SC once per day on days 4 to 13
 
−
**Patients at least 75 kg: 480 mcg SC once per day on days 4 to 13
 
−
'''14-day cycle for 6 cycles''', next cycle to start as long as WBC count is greater than 2.5 x 10<sup>9</sup>/L and platelets greater than 80 x 10<sup>9</sup>/L
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with initial bulky disease (mass conglomerate at least 7.5 cm): [[#Radiation_therapy_88|RT]] x 36 Gy to extranodal sites of disease when possible
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''NHL-B1:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. [http://www.bloodjournal.org/content/104/3/626.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14982884 PubMed]
+
# '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149
−
==CHOEP-21 {{#subobject:c621ab|Regimen=1}}==
+
==SMILE {{#subobject:db70b|Regimen=1}}==
−
CHOEP-21: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone every '''<u>21</u>''' days
+
SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide
−
<br>CHOPE
 
−
<br>VACOP
 
−
===Example orders===
 
−
*[[Example orders for CHOEP in lymphoma]]
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:fan248|Variant=1}}===
+
===Regimen {{#subobject:9874b6|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
 
−
|1993-2000
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|1. [[#CHOEP-14|CHOEP-14]]<br>2. [[#CHOP|CHOP-21]]<br>3. [[#CHOP-14_99|CHOP-14]]
 
−
|Not reported by subgroup
 
−
|Not reported by subgroup
 
−
|}
 
−
''This regimen was used in 20 ALCL patients in the NHL-B1 trial. The authors did not report a subgroup analysis for this minority population.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] is by discretion of ordering physician
 
−
'''21-day cycle for 6 cycles''', next cycle to start as long as WBC count is greater than 2.5 x 10<sup>9</sup>/L and platelets greater than 80 x 10<sup>9</sup>/L
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with initial bulky disease (mass conglomerate at least 7.5 cm): [[#Radiation_therapy_88|RT]] x 36 Gy to extranodal sites of disease when possible
 
−
</div></div>
 
−
===References===
 
−
# '''NHL-B1:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. [http://www.bloodjournal.org/content/104/3/626.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14982884 PubMed]
 
−
==CHOP {{#subobject:4ca454|Regimen=1}}==
 
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<br>CHOP-21
 
−
<br>ACOP
 
−
<br>CAVP
 
−
<br>COPA
 
−
<br>VACP
 
−
<br>VCAP
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, capped vincristine {{#subobject:9e662b|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 152: Line 60:
 
!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/PMC6436818/ Horwitz et al. 2018 (ECHELON-2)]
+
|[http://www.bloodjournal.org/content/120/15/2973.long Kwong et al. 2012]
−
|2013-2016
+
|2005-2012
−
|style="background-color:#1a9851"|Phase 3 (C)
+
|style="background-color:#91cf61"|Phase 2
−
|[[#BV-CHP|BV-CHP]]
+
|style="background-color:#d3d3d3"|
−
| style="background-color:#d73027" |Inferior OS
+
|style="background-color:#d3d3d3"|
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/22/21/5223.long Li et al. 2016 (CTTNKTL-III/IV)]
 +
|2011-2014
 +
|style="background-color:#1a9851"|Phase 4 (E-switch-ic)
 +
|[[#DDGP|DDGP]]
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 +
''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, flat-dose vincristine {{#subobject:9e770b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
 
−
|1993-2000
 
−
|style="background-color:#91cf61"|Phase 3, <20 pts in arm (C)
 
−
|1. [[#CHOEP-21|CHOEP-21]]<br>2. [[#CHOP-14_99|CHOP-14]]
 
−
|Not reported by subgroup
 
−
|Not reported by subgroup
 
−
|}
 
−
''This regimen was used in 14 ALCL patients in NHL-B1. The authors did not report a subgroup analysis for this minority population.''
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4
−
====Supportive therapy====
 
−
*At the discretion of ordering physician: [[Filgrastim (Neupogen)]] 300 mcg (for patients less than 75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''NHL-B1:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. [http://www.bloodjournal.org/content/104/3/626.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14982884 PubMed]
 
−
# '''ECHELON-2:''' Horwitz S, O'Connor OA, Pro B, Illidge T, Fanale M, Advani R, Bartlett NL, Christensen JH, Morschhauser F, Domingo-Domenech E, Rossi G, Kim WS, Feldman T, Lennard A, Belada D, Illés Á, Tobinai K, Tsukasaki K, Yeh SP, Shustov A, Hüttmann A, Savage KJ, Yuen S, Iyer S, Zinzani PL, Hua Z, Little M, Rao S, Woolery J, Manley T, Trümper L; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019 Jan 19;393(10168):229-240. Epub 2018 Dec 4. Erratum in: Lancet. 2019 Jan 19;393(10168):228. [https://doi.org/10.1016/S0140-6736(18)32984-2 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436818/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30522922 PubMed] NCT01777152
 
−
==DA-EPOCH {{#subobject:6c5911|Regimen=1}}==
 
−
DA-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:659929|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697904/ Dunleavy et al. 2016 (NCI 93-C-0133<sub>ALCL</sub>)]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: this should be considered a substudy under the master protocol NCI 93-C-0133.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>)
+
*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1
−
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>)
+
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with mesna'''
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 2 hours once on day 5
+
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
+
**Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
−
====Glucocorticoid therapy====
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
+
*[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]]
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
+
**Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
−
*[[Omeprazole (Prilosec)]] 20 mg (or equivalent) PO once per day
+
*[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with [[Ifosfamide (Ifex)]]'''
−
*[[Docusate (Colace)]] (dose not specified) and [[Sennosides (Senna)]] 2 tablets PO twice per day as needed for constipation
+
*Hydration with normal saline (no volume specified) every 8 hours on the day prior to [[Methotrexate (MTX)]]
−
*Lactulose 20 g PO every 6 hours as needed for constipation
+
*Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of greater than or equal to 3 liters per day on days 1 to 4
−
*Hepatitis B surface antigen positive patients: received daily [[:Category:Antivirals|antiviral]] therapy until 8 weeks after completion of chemotherapy
+
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
−
'''21-day cycle for 6 to 8 cycles'''
+
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] or [[Pentamidine (Nebupent)]] for PJP prophylaxis
−
====Dose modifications====
+
*[[Famotidine (Pepcid)]] and potassium slow release tablets (no dose specified) "for [[Dexamethasone (Decadron)]]" on days 2 to 4
−
*Start cycle 1 as described above.
+
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
−
*Obtain CBCs twice per week for nadir measurements.
+
*[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
−
*If nadir ANC greater than 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
+
'''28-day cycle for up to 6 cycles (see note)'''
−
*If nadir ANC less than 500/uL, use same doses as last cycle.
 
−
*If nadir platelet count less than 25 x 10<sup>9</sup>/L, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''NCI 93-C-0133:''' Dunleavy K, Pittaluga S, Shovlin M, Roschewski M, Lai C, Steinberg SM, Jaffe ES, Wilson WH. Phase II trial of dose-adjusted EPOCH in untreated systemic anaplastic large cell lymphoma. Haematologica. 2016 Jan;101(1):e27-9. [http://www.haematologica.org/content/101/1/e27.long link to original article] '''refers to protocol in [https://doi.org/10.1056/NEJMoa1214561 Dunleavy et al. 2013]''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697904/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26518748 PubMed] NCT00001337
+
# Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed]
−
=Relapsed or refractory, salvage therapy=
+
# '''CTTNKTL-III/IV:''' Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. [http://clincancerres.aacrjournals.org/content/22/21/5223.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/27060152 PubMed] NCT01501149
−
==Brentuximab vedotin monotherapy {{#subobject:e32d67|Regimen=1}}==
+
=Relapsed or refractory=
 +
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
 +
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 16 cycles {{#subobject:46fbc9|Variant=1}}===
+
===Regimen {{#subobject:bfe434|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://doi.org/10.1200/jco.2011.38.0402 Pro et al. 2012 (SG035-0004)]
+
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
−
|2009-2010
+
|2004-2009
−
|style="background-color:#91cf61"|Phase 2 (RT)
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#b3e2cd">
+
{{#lst:Allogeneic HSCT|bfe434}}
−
====Antibody-drug conjugate therapy====
+
</div></div>
−
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
+
===References===
−
'''21-day cycle for up to 16 infusions'''
+
<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
−
</div></div><br>
+
# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
 +
==Pembrolizumab monotherapy {{#subobject:84ac5y|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, bridge to transplant {{#subobject:48bjc9|Variant=1}}===
+
===Regimen {{#subobject:ga3na4|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659993/ Gibb et al. 2012]
+
|[https://doi.org/10.1182/blood-2016-12-756841 Kwong et al. 2017]
−
|style="background-color:#91cf61"|Named Patient Programme
+
| style="background-color:#ffffbe" |Case series
 
|-
 
|-
 
|}
 
|}
 +
''Note: prospective trials are underway.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Antibody-drug conjugate therapy====
+
====Immunotherapy====
−
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
+
*[[Pembrolizumab (Keytruda)]] 2 mg/kg IV once on day 1
−
'''21-day cycles until transplant'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, indefinite {{#subobject:46nz3b|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731651/ Gopal et al. 2012 (SGN35-006)]
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in subgroup
 
−
|-
 
−
|}
 
−
''Note: SGN35-006 is a re-treatment trial; all patients were previously exposed to brentuximab vedotin. Patients who had received the 1.2 mg/kg dose on a prior trial also received that dose at re-treatment.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
 
 
'''21-day cycles'''
 
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''SGN35-006:''' Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. [http://www.bloodjournal.org/content/120/3/560.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731651/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22510871 PubMed] NCT01026233
+
#Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Epub 2017 Feb 10. [https://doi.org/10.1182/blood-2016-12-756841 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28188133/ PubMed]
−
## '''Update:''' Bartlett NL, Chen R, Fanale MA, Brice P, Gopal A, Smith SE, Advani R, Matous JV, Ramchandren R, Rosenblatt JD, Huebner D, Levine P, Grove L, Forero-Torres A. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol. 2014 Mar 19;7:24. [http://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-7-24 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994656/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24642247 PubMed]
+
==SMILE {{#subobject:db70b|Regimen=1}}==
−
# '''SG035-0004:''' Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Yang Y, Sievers EL, Kennedy DA, Shustov A. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2190-6. Epub 2012 May 21. [https://doi.org/10.1200/jco.2011.38.0402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22614995 PubMed] NCT00866047
+
SMILE: '''<u>S</u>'''teroid (Dexamethasone), '''<u>M</u>'''ethotrexate, '''<u>I</u>'''fosfamide, '''<u>L</u>'''-asparaginase, '''<u>E</u>'''toposide
−
<!-- ## '''Update: Abstract:''' Barbara Pro, MD, Ranjana Advani, MD, Pauline Brice, MD, Nancy L. Bartlett, MD, Joseph D. Rosenblatt, MD, Tim Illidge, Jeffrey Matous, MD, Radhakrishnan Ramchandern, MD, Michelle A. Fanale, MD, Joseph M. Connors, MD, Yinghui Wang, MS, Dirk Huebner, MD, Dana A. Kennedy, PharmD, BCOP and Andrei R. Shustov, MD. Four-Year Survival Data from an Ongoing Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma. ASH Annual Meeting 2014, Abstract 3095 [https://ash.confex.com/ash/2014/webprogram/Paper67039.html link to abstract] -->
 
−
## '''Update:''' Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, Fenton K, Huebner D, Pinelli JM, Kennedy DA, Shustov A. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017 Dec 21;130(25):2709-2717. Epub 2017 Oct 3. [https://doi.org/10.1182/blood-2017-05-780049 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5746164/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28974506 PubMed]
 
−
# Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. [http://www.haematologica.org/content/98/4/611.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659993/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23065511 PubMed]
 
−
# '''Retrospective:''' Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. Epub 2014 Feb 24. [http://www.tandfonline.com/doi/full/10.3109/10428194.2013.876496 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24359243 PubMed]
 
−
==DHAP {{#subobject:5a2988|Regimen=1}}==
 
−
DHAP: '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (cytarabine), '''<u>P</u>'''latinol (cisplatin)
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:d2a377|Variant=1}}===
+
===Regimen {{#subobject:9874b6|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 33%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 33%"|Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
+
|-
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
|[https://doi.org/10.1111/j.1349-7006.2008.00768.x Yamaguchi et al. 2008]
 +
|2005-2006
 +
| style="background-color:#ffffbe" |Phase 1
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
+
|[http://www.bloodjournal.org/content/120/15/2973.long Kwong et al. 2012]
−
|2003-2011
+
|2005-2012
−
|style="background-color:#91cf61"|Phase 3, <20 in this arm (C)
+
|style="background-color:#91cf61"|Phase 2
−
|[[Anaplastic_large_cell_lymphoma#GDP|GDP]]
 
−
|style="background-color:#eeee01"|Non-inferior ORR
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: [[Asparaginase (Elspar)]] was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include [[Pegaspargase (Oncaspar)]] or [[Asparaginase Erwinia chrysanthemi (Erwinaze)]]. Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2008, describe 28-day cycles.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
+
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 2 to 4
−
'''21-day cycle for up to 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
 
−
# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
 
−
==GDP {{#subobject:21f926|Regimen=1}}==
 
−
GDP: '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ce43d5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!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.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
 
−
|2003-2011
 
−
|style="background-color:#91cf61"|Phase 3, <20 pts in this arm (E-switch-ic)
 
−
|[[#DHAP|DHAP]]
 
−
|style="background-color:#eeee01"|Non-inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
*[[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 6 hours once on day 1
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with mesna'''
−
====Glucocorticoid therapy====
+
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
+
**Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
−
'''21-day cycle for up to 3 cycles'''
+
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 4
−
</div></div>
+
====Supportive therapy====
−
===References===
+
*[[Folinic acid (Leucovorin)]] 45 mg PO every 6 hours on days 2 to 4 (or until serum methotrexate level is below the toxic range), starting 24 hours after completion of [[Methotrexate (MTX)]]
−
<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
+
**Methotrexate levels checked at 24, 48, and 72 hours after methotrexate is given, or until methotrexate levels fall below toxic range. Folinic acid should be continued until methotrexate levels are below toxic range.
−
# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
+
*[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV over 6 hours once per day on days 2 to 4, '''given with [[Ifosfamide (Ifex)]]'''
−
=Consolidation after salvage therapy=
+
*Hydration with normal saline (no volume specified) every 8 hours on the day prior to [[Methotrexate (MTX)]]
−
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
+
*Patients told to drink at least 2 liters of fluid per day on days 1 to 4; target urine output of greater than or equal to 3 liters per day on days 1 to 4
−
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
+
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6, given until ANC greater than 1000/uL
−
<div class="toccolours" style="background-color:#eeeeee">
+
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] or [[Pentamidine (Nebupent)]] for PJP prophylaxis
−
===Regimen {{#subobject:bfe434|Variant=1}}===
+
*[[Famotidine (Pepcid)]] and potassium slow release tablets (no dose specified) "for [[Dexamethasone (Decadron)]]" on days 2 to 4
−
{| class="wikitable" style="width: 40%; text-align:center;"
+
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg PO once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
−
!style="width: 25%"|Study
+
*[[Hydrocortisone (Cortef)]] 100 mg IV once per day on days 8, 10, 12, 14, 16, 18, 20, prior to [[Asparaginase (Elspar)]]
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
'''28-day cycle for up to 6 cycles (see note)'''
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|bfe434}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
+
# '''Phase 1:''' Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. [https://doi.org/10.1111/j.1349-7006.2008.00768.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18294294 PubMed] content property of [http://hemonc.org HemOnc.org]
−
# '''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
+
# Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. [http://www.bloodjournal.org/content/120/15/2973.long link to original article] [http://www.bloodjournal.org/content/120/15/2973/suppl/DC1 supplemental materials] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/22919026 PubMed]
−
[[Category:Anaplastic large cell lymphoma regimens]]
+
[[Category:NK- and T-cell lymphoma regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:T-cell lymphomas]]
 
[[Category:T-cell lymphomas]]

Revision as of 12:04, 29 October 2022

Back to Top

Section editor transclusions

0 regimens on this page
0 variants on this page


Note: a variant of this disease, aggressive NK-cell leukemia, is usually considered a separate entity (somewhat analogous to plasma cell leukemia and multiple myeloma). There are no prospective trials reported for this variant.

Guidelines

ESMO

"How I Treat"

NCCN

Untreated

DDGP

DDGP: Dexamethasone, DDP (Cisplatin), Gemcitabine, Pegaspargase

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Li et al. 2016 (CTTNKTL-III/IV) 2011-2014 Phase 4 (E-switch-ic) SMILE Seems to have superior OS
OS24: 74% vs 45%

Note: dosing information is from the NCT record.

Glucocorticoid therapy

Chemotherapy

21-day cycle for at least 3 cycles

References

  1. CTTNKTL-III/IV: Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. link to original article does not contain dosing details PubMed NCT01501149

SMILE

SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kwong et al. 2012 2005-2012 Phase 2
Li et al. 2016 (CTTNKTL-III/IV) 2011-2014 Phase 4 (E-switch-ic) DDGP Seems to have inferior OS

Note: Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze). Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2011, describe 28-day cycles.

Glucocorticoid therapy

Chemotherapy

  • Methotrexate (MTX) 2000 mg/m2 IV over 6 hours once on day 1
  • Ifosfamide (Ifex) 1500 mg/m2 IV over 6 hours once per day on days 2 to 4, given with mesna
  • Asparaginase (Elspar) 6000 units/m2 IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
    • Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
  • Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 2 to 4

Supportive therapy

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

References

  1. Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. link to original article supplemental materials contains dosing details in supplement PubMed
  2. CTTNKTL-III/IV: Li X, Cui Y, Sun Z, Zhang L, Li L, Wang X, Wu J, Fu X, Ma W, Zhang X, Chang Y, Nan F, Li W, Su L, Wang J, Xue H, Zhang M. DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China. Clin Cancer Res. 2016 Nov 1;22(21):5223-5228. Epub 2016 Apr 8. link to original article PubMed NCT01501149

Relapsed or refractory

FluBuCy, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen

Study Years of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-2009 Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. DSHNHL R3: Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. link to original article link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330

Pembrolizumab monotherapy

Regimen

Study Evidence
Kwong et al. 2017 Case series

Note: prospective trials are underway.

Immunotherapy

21-day cycles

References

  1. Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. Epub 2017 Feb 10. link to original article PubMed

SMILE

SMILE: Steroid (Dexamethasone), Methotrexate, Ifosfamide, L-asparaginase, Etoposide

Regimen

Study Years of enrollment Evidence
Yamaguchi et al. 2008 2005-2006 Phase 1
Kwong et al. 2012 2005-2012 Phase 2

Note: Asparaginase (Elspar) was discontinued by the manufacturer in December 2012, and is now essentially out of stock. Alternatives include Pegaspargase (Oncaspar) or Asparaginase Erwinia chrysanthemi (Erwinaze). Neither paper nor supplement specified the length of each cycle, but other SMILE regimens, e.g. Yamaguchi et al. 2008, describe 28-day cycles.

Glucocorticoid therapy

Chemotherapy

  • Methotrexate (MTX) 2000 mg/m2 IV over 6 hours once on day 1
  • Ifosfamide (Ifex) 1500 mg/m2 IV over 6 hours once per day on days 2 to 4, given with mesna
  • Asparaginase (Elspar) 6000 units/m2 IV over 2 hours once per day on days 8, 10, 12, 14, 16, 18, 20
    • Skin test done for asparaginase before each dose; Asparaginase Erwinia chrysanthemi used for patients who developed sensitivity to L-asparaginase from E. coli
  • Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 2 to 4

Supportive therapy

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

References

  1. Phase 1: Yamaguchi M, Suzuki R, Kwong YL, Kim WS, Hasegawa Y, Izutsu K, Suzumiya J, Okamura T, Nakamura S, Kawa K, Oshimi K. Phase I study of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemia. Cancer Sci. 2008 May;99(5):1016-20. Epub 2008 Feb 19. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
  2. Kwong YL, Kim WS, Lim ST, Kim SJ, Tang T, Tse E, Leung AY, Chim CS; Asia Lymphoma Study Group. SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group. Blood. 2012 Oct 11;120(15):2973-80. Epub 2012 Aug 23. link to original article supplemental materials contains dosing details in supplement PubMed
Retrieved from "https://hemonc.org/w/index.php?title=Staging_page&oldid=63619"