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>
−
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? Please go to the [[Chronic_lymphocytic_leukemia|main CLL/SLL regimen page]] to find other regimens.
+
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Non-small_cell_lung_cancer|main NSCLC page]] for current regimens.
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
Line 10: Line 10:
 
|}  
 
|}  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
−
=First-line therapy=
+
=Neoadjuvant therapy=
−
==CAP {{#subobject:6a668f|Regimen=1}}==
+
==MIC {{#subobject:6be6b3|Regimen=1}}==
−
CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
+
MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:e29575|Variant=1}}===
+
===Regimen {{#subobject:c1b1e|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 22: Line 22:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.3109/10428199009069292 Keating et al. 1990 (SWOG-7410)]
+
|[https://doi.org/10.1056/NEJM199401203300301 Rosell et al. 1994]
−
|1974-1979
+
|1989-1991
−
| style="background-color:#91cf61" |Phase 2
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
| style="background-color:#d3d3d3" |
+
|[[Non-small_cell_lung_cancer_-_null_regimens#No_neoadjuvant_therapy|No preoperative therapy]]
−
| style="background-color:#d3d3d3" |
+
| style="background-color:#1a9850" |Superior OS
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(96)91681-5 Johnson et al. 1996]
+
|[https://doi.org/10.1200/JCO.2002.20.1.247 Depierre et al. 2002]
−
|1990-1992
+
|1991-1997
−
|style="background-color:#1a9851"|Phase 3 (C)
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#Fludarabine_monotherapy|Fludarabine]]
+
|[[Non-small_cell_lung_cancer_-_null_regimens#No_neoadjuvant_therapy|No preoperative therapy]]
−
|style="background-color:#d73027"|Inferior TTP<sup>1</sup>
+
| style="background-color:#ffffbf" |Seems not superior
−
|-
 
−
|rowspan=2|[http://www.bloodjournal.org/content/98/8/2319.long Leporrier et al. 2001 (FCGCLL 1996)]
 
−
|rowspan=2|1990-1998
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#CHOP|CHOP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Fludarabine_monotherapy|Fludarabine]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>The inferior endpoint in Johnson et al. 1996 was only observed in this subgroup, not pretreated patients.''<br>
 
−
''Note: To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1
−
====Glucocorticoid therapy====
+
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
====Supportive therapy====
−
'''1-month cycle for 6 cycles'''
+
*[[Mesna (Mesnex)]] 1000 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''admixed with ifosfamide'''
 +
*[[Metoclopramide (Reglan)]] 3 mg/kg IV, given 30 minutes prior and 90 minutes after chemotherapy
 +
*[[Dexamethasone (Decadron)]] 20 mg IV once, given 30 minutes prior to chemotherapy
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Lung_cancer_surgery|Surgery]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''SWOG-7410:''' Keating MJ, Hester JP, McCredie KB, Burgess MA, Murphy WK, Freireich EJ. Long-term results of CAP therapy in chronic lymphocytic leukemia. Leuk Lymphoma. 1990;2(6):391-7. [https://doi.org/10.3109/10428199009069292 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27457043 PubMed]
+
# Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, Mate JL, Li S, Roig J, Olazábal A, Canela M, Ariza A, Skacel Z, Morera-Prat J, Abad A. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994 Jan 20;330(3):153-8. [https://doi.org/10.1056/NEJM199401203300301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8043059 PubMed]
−
# Johnson S, Smith AG, Löffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W; French Cooperative Group on CLL. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. Lancet. 1996 May 25;347(9013):1432-8. [https://doi.org/10.1016/S0140-6736(96)91681-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8676625 PubMed]
+
# Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, Braun D, Breton JL, Lemarié E, Gouva S, Paillot N, Bréchot JM, Janicot H, Lebas FX, Terrioux P, Clavier J, Foucher P, Monchâtre M, Coëtmeur D, Level MC, Leclerc P, Blanchon F, Rodier JM, Thiberville L, Villeneuve A, Westeel V, Chastang C; IFCT. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol. 2002 Jan 1;20(1):247-53. [https://doi.org/10.1200/JCO.2002.20.1.247 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11773176 PubMed]
−
# '''FCGCLL 1996:''' Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C; French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001 Oct 15;98(8):2319-25. [http://www.bloodjournal.org/content/98/8/2319.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11588025 PubMed]
+
=Adjuvant therapy=
−
==Chlorambucil monotherapy {{#subobject:69ac3|Regimen=1}}==
+
==Radiation therapy {{#subobject:743aa8|Regimen=1}}==
 +
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 0.1 mg/kg {{#subobject:512687|Variant=1}}===
+
===Regimen {{#subobject:426dfc|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 68: Line 65:
 
!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/S0140-6736(86)91663-6 Binet et al. 1986 (FRE-CLL-80)]
+
|[https://doi.org/10.1056/nejm200010263431703 Keller et al. 2000 (ECOG E3590)]
−
|1980-1985
+
|1991-1997
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Chronic_lymphocytic_leukemia#Observation|Observation]]<sup>1</sup>
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(86)91663-6 Binet et al. 1986 (FRE-CLL-80)]
 
−
|1980-1985
 
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#CVP|CVP]]<sup>1</sup>
+
|[[#Cisplatin_.26_Etoposide_.28EP.29_.26_RT|EP & RT]]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+
|style="background-color:#ffffbf"|Did not meet endpoint of OS
−
|-
 
−
|[https://doi.org/10.1056/NEJM199805213382104 Dighiero et al. 1998 (FRE-CLL-85)]
 
−
|1985-1990
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Chronic_lymphocytic_leukemia#Observation|Observation]]
 
−
|style="background-color:#91cf60"|Seems to have superior PFS
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>In FRE-CLL-80, this was the experimental arm for Binet Stage A and the control arm for Binet Stage B.''<br>
+
<div class="toccolours" style="background-color:#cbd5e8">
−
''Note: FRE-CLL-85 is one of two trials reported in Dighiero et al. 1998; the other was comparing chlorambucil & prednisone vs. observation.''
+
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]]
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Radiotherapy====
−
*[[Chlorambucil (Leukeran)]] 0.1 mg/kg PO once per day
+
*[[External_beam_radiotherapy|Radiation therapy]], 1.8 Gy fractions x 28 fractions (total dose: 50.4 Gy)
−
'''Continued indefinitely'''
+
'''5-week course'''
−
</div></div><br>
+
</div></div>
 +
===References===
 +
# '''ECOG E3590:''' Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH; [[Study_Groups#ECOG|ECOG]]. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000 Oct 26;343(17):1217-22. [https://doi.org/10.1056/nejm200010263431703 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11071672 PubMed]
 +
=Induction therapy for locally advanced disease=
 +
==MIC {{#subobject:ebf0c1|Regimen=1}}==
 +
MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
 +
<br>MIP: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 0.4 mg/kg {{#subobject:ca331d|Variant=1}}===
+
===Regimen {{#subobject:d1267e|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 103: Line 96:
 
!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.2008.20.8389 Knauf et al. 2009]
+
|[https://doi.org/10.1023/a:1008319506107 Sculier et al. 1999]
−
|2002-2006
+
|1989-1996
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdh105 Sculier et al. 2004]
 +
|1996-2002
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#Bendamustine_monotherapy|Bendamustine]]
+
|[[#SuperMIP_99|SuperMIP]]
−
|style="background-color:#d73027"|Inferior PFS
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen was intended for previously untreated CLL patients up to 75 years of age with [[#Binet_staging_.281981.29|Binet stage]] B or C disease in need for treatment per the [[#NCI_Sponsored_Working_Group_Criteria_.281996.29|NCI-WG guidelines]] or [[#International_Workshop_on_Chronic_Lymphocytic_Leukemia_guidelines_.282008.29|IWCLL guidelines]].''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 0.4 mg/kg PO once per day on days 1 to 2, 15 to 16
+
*[[Mitomycin (Mutamycin)]]
−
'''28-day cycle for up to 6 cycles'''
+
*[[Ifosfamide (Ifex)]]
−
</div></div><br>
+
*[[Cisplatin (Platinol)]]
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Sculier et al. 1999: MIP x 3 versus [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
 +
*Sculier et al. 2004: [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
 +
</div></div>
 +
===References===
 +
# Sculier JP, Paesmans M, Lafitte JJ, Baumöhl J, Thiriaux J, van Cutsem O, Recloux P, Bureau G, Berchier MC, Zacharias C, Mommen P, Bosschaerts T, Berghmans T, van Houtte P, Ninane V, Klastersky J; European Lung Cancer Working Party. A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. Ann Oncol. 1999 Mar;10(3):295-303. [https://doi.org/10.1023/a:1008319506107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10355573 PubMed]
 +
# Sculier JP, Lafitte JJ, Berghmans T, Van Houtte P, Lecomte J, Thiriaux J, Efremidis A, Koumakis G, Giner V, Richez M, Corhay JL, Wackenier P, Lothaire P, Paesmans M, Mommen P, Ninane V; European Lung Cancer Working Party. A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer. Ann Oncol. 2004 Mar;15(3):399-409. [https://doi.org/10.1093/annonc/mdh105 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14998841 PubMed]
 +
==PEV {{#subobject:ebf0c1|Regimen=1}}==
 +
PEV: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>V</u>'''inblastine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, 0.4 mg/kg, with dose escalation {{#subobject:1ac4ad|Variant=1}}===
+
===Regimen {{#subobject:d1267e|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 125: Line 134:
 
!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/114/16/3382.long Eichhorst et al. 2009 (GCLLSG CLL5)]
+
|[https://doi.org/10.1097/00000421-200206000-00007 Kim et al. 2002]
−
|1999-2004
+
|1988-1992
−
|style="background-color:#1a9851"|Phase 3 (C)
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#Fludarabine_monotherapy|Fludarabine]]
+
|[[Non-small_cell_lung_cancer_-_null_regimens#No_induction|No]] induction
−
|style="background-color:#ffffbf"|Did not meet primary endpoints of PFS/OS
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen was intended for untreated patients between 65 and 80 years with [[#Binet_staging_.281981.29|Binet stage]] C, or [[#Binet_staging_.281981.29|Binet stage]] B or A if they had rapid disease progression (lymphocyte doubling time less than 3 months) or symptoms from enlarged lymph nodes and organs, or if they had severe B symptoms.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] as follows:
+
*[[Cisplatin (Platinol)]]
−
**Cycle 1: 0.4 mg/kg PO once on day 1
+
*[[Etoposide (Vepesid)]]
−
**To be increased as tolerated by 0.1 mg/kg each cycle, up to a maximum of 0.8 mg/kg PO once on day 1
+
*[[Vinblastine (Velban)]]
−
'''14-day cycle for up to 24 cycles'''
+
</div>
−
</div></div><br>
+
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
 +
</div></div>
 +
===References===
 +
# Kim TY, Yang SH, Lee SH, Park YS, Im YH, Kang WK, Ha SH, Park CI, Heo DS, Bang YJ, Kim NK. A phase III randomized trial of combined chemoradiotherapy versus radiotherapy alone in locally advanced non-small-cell lung cancer. Am J Clin Oncol. 2002 Jun;25(3):238-43. [https://doi.org/10.1097/00000421-200206000-00007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12040280 PubMed]
 +
=Definitive therapy for locally advanced disease=
 +
==MVP & RT {{#subobject:10d15d|Regimen=1}}==
 +
MVP & RT: '''<u>M</u>'''itomycin, '''<u>V</u>'''indesine, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #4, 0.5 mg/kg {{#subobject:ad0508|Variant=1}}===
+
===Regimen {{#subobject:8fd069|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 149: Line 165:
 
!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/10.1056/NEJMoa1313984 Goede et al. 2014 (GCLLSG CLL11)]
+
|[https://doi.org/10.1200/JCO.1999.17.9.2692 Furuse et al. 1999 (JCOG9202)]
−
|rowspan=2|2010-2012
+
|1992-1994
−
|rowspan = "2" style="background-color:#1a9851"|Phase 3 (C)
+
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
−
|1. [[Chronic_lymphocytic_leukemia#Chlorambucil_.26_Obinutuzumab_.28GClb.29|Chlorambucil & Obinutuzumab]]
+
|[[#MVP_.28Vindesine.29_88|MVP]], then [[#Radiation_therapy_88|RT]]
−
|style="background-color:#d73027"|Inferior OS
+
| style="background-color:#91cf60" |Seems to have superior OS
−
|-
 
−
|2. [[Chronic_lymphocytic_leukemia#Chlorambucil_.26_Rituximab_.28RClb.29|Chlorambucil & Rituximab]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722809/ Burger et al. 2015 (RESONATE-2)]
 
−
|2013-NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Chronic_lymphocytic_leukemia#Ibrutinib_monotherapy|Ibrutinib]]
 
−
|style="background-color:#d73027"|Inferior OS<sup>1</sup>
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy for RESONATE-2 is based on the 2019 update.''<br>
 
−
''Note: Patients enrolled on RESONATE-2 were allowed to increase the dose up to 0.8 mg/kg if "there was not an unacceptable level of toxic effects."''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 0.5 mg/kg PO once per day on days 1 & 15
+
*[[Mitomycin (Mutamycin)]]
−
'''28-day cycle for 6 to 12 cycles'''
+
*[[Vindesine (Eldisine)]]
−
</div></div><br>
+
*[[Cisplatin (Platinol)]]
 +
====Radiotherapy====
 +
*[[External beam radiotherapy]]
 +
</div></div>
 +
===References===
 +
# '''JCOG9202:''' Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. [https://doi.org/10.1200/JCO.1999.17.9.2692 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561343 PubMed]
 +
=Consolidation or maintenance after definitive therapy for inoperable disease=
 +
==Bacillus Calmette-Guérin (BCG) monotherapy==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #5, 0.8 mg/kg {{#subobject:cea31d|Variant=1}}===
+
===Regimen===
 
{| 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 181: Line 193:
 
!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.2008.20.8389 Knauf et al. 2009]
+
|[https://doi.org/10.1016/S0140-6736(76)90213-0 Pines 1976]
−
|2002-2006
+
|1970-1973
−
|style="background-color:#1a9851"|Phase 3 (C)
+
|style="background-color:#1a9851"|Randomized (C)
−
|[[Chronic_lymphocytic_leukemia#Bendamustine_monotherapy|Bendamustine]]
+
|[[Non-small_cell_lung_cancer#Observation_2|Observation]]
−
|style="background-color:#d73027"|Inferior PFS
+
| style="background-color:#91cf60" |Seems to have superior OS
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420789/ Chanan-Khan et al. 2017 (ORIGIN)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lenalidomide_monotherapy|Lenalidomide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen was intended for previously untreated CLL patients up to 75 years of age with [[#Binet_staging_.281981.29|Binet stage]] B or C disease in need for treatment per the [[#NCI_Sponsored_Working_Group_Criteria_.281996.29|NCI-WG guidelines]] or [[#International_Workshop_on_Chronic_Lymphocytic_Leukemia_guidelines_.282008.29|IWCLL guidelines]].''
+
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Regimen_classes#Radiotherapy-based_regimen|RT]]
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Immunotherapy====
−
*[[Chlorambucil (Leukeran)]] 0.8 mg/kg PO once per day on days 1 & 15
+
*[[Bacillus Calmette-Guérin (BCG)]]
−
'''28-day cycle for up to 6 cycles (Knauf et al. 2009) or indefinitely (ORIGIN)'''
+
</div></div>
−
</div></div><br>
+
===References===
 +
# Pines A. A 5-year controlled study of BCG and radiotherapy inoperable lung cancer. Lancet. 1976 Feb 21;1(7956):380-1. [https://doi.org/10.1016/S0140-6736(76)90213-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/55647 PubMed]
 +
=Advanced or metastatic disease, first-line=
 +
==CAMP {{#subobject:2d62ce|Regimen=1}}==
 +
CAMP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rocarbazine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #6, 10 mg/m<sup>2</sup> {{#subobject:ec8dfe|Variant=1}}===
+
===Regimen {{#subobject:f79237|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/10.1016/S0140-6736(07)61125-8 Catovsky et al. 2007 (LRF CLL4)]
+
|[https://jamanetwork.com/journals/jama/article-abstract/362874 Bitran et al. 1978]
−
|rowspan=2|1999-2004
+
| style="background-color:#91cf61" |Non-randomized
−
|rowspan = "2" style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#FC|FC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Fludarabine_monotherapy|Fludarabine]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(15)60027-7 Hillmen et al. 2015 (COMPLEMENT 1)]
 
−
|2008-2011
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Chronic_lymphocytic_leukemia#Chlorambucil_.26_Ofatumumab|Chlorambucil & Ofatumumab]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 10 mg/m<sup>2</sup> PO once per day on days 1 to 7
+
*[[Cyclophosphamide (Cytoxan)]]
−
====Supportive therapy====
+
*[[Doxorubicin (Adriamycin)]]
−
*Per '''Catovsky et al. 2007''': Patients with stage C disease (hemoglobin less than 10 g/dL or platelet count less than 100 x 10<sup>9</sup>/L) received [[Prednisolone (Millipred)]] 30 mg/m<sup>2</sup> PO once per day for 3 weeks, then 1 week taper before starting [[Chlorambucil (Leukeran)]] to reduce its myelotoxicity
+
*[[Methotrexate (MTX)]]
−
'''28-day cycle for up to 12 cycles'''
+
*[[Procarbazine (Matulane)]]
−
</div></div><br>
+
</div></div>
 +
===References===
 +
# Bitran JD, Desser RK, DeMeester T, Golomb HM. Metastatic non-oat-cell bronchogenic carcinoma: therapy with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP). JAMA. 1978 Dec 15;240(25):2743-6. [https://jamanetwork.com/journals/jama/article-abstract/362874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/713008 PubMed]
 +
# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
 +
==CAP (Platinol) {{#subobject:379e5f|Regimen=1}}==
 +
CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #7, 40 mg/m<sup>2</sup> {{#subobject:e1b84b|Variant=1}}===
+
===Regimen {{#subobject:e7847b|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 241: Line 244:
 
!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/10.1056/NEJM200012143432402 Rai et al. 2000 (CALGB 9011)]
+
|[https://doi.org/10.1200/jco.1984.2.5.391 Robert et al. 1984]
−
|rowspan=2|1990-1994
+
|1978-1981
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|1. [[#Chlorambucil_.26_Fludarabine_99|Chlorambucil & Fludarabine]]
+
|1. [[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_99|Cyclophosphamide & Doxorubicin (AC)]]<br>2. [[#CAMF_99|CAMF]]
−
|style="background-color:#d3d3d3"|Not reported
+
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
|-
 
|-
−
|2. [[#Fludarabine_monotherapy|Fludarabine]]
+
|[https://doi.org/10.1200/JCO.1986.4.4.502 Miller et al. 1986 (SWOG S8012)]
−
|style="background-color:#d73027"|Inferior PFS
+
|1980-1983
−
|-
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[https://doi.org/10.1200/jco.2007.12.9098 Hillmen et al. 2007 (CAM 307)]
+
|1. [[#FOMi_88|FOMi]]<br>2. [[#FOMi.2FCAP_88|FOMi/CAP]]
−
|2001-2004
+
| style="background-color:#fc8d59" |Seems to have inferior OS
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Chronic_lymphocytic_leukemia#Alemtuzumab_monotherapy|Alemtuzumab]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
−
''Note: In CALGB 9011, this regimen was intended for previously untreated patients with CLL who were high-risk ([[#Original_Rai_staging_.281975.29|Rai stage]] III or IV) or intermediate-risk ([[#Original_Rai_staging_.281975.29|Rai stage]] I or II) if they had at least one of the following: disease-related symptoms such as weight loss, extreme fatigue, night sweats, or fever without evidence of infection; massive or progressive splenomegaly or lymphadenopathy, or more than a 50 percent increase in the number of peripheral-blood lymphocytes over a 2-month period or an anticipated doubling of these cells within less than 12 months. In CAM 307, this regimen was intended for patients who were at least 18 years old with flow cytometry–confirmed diagnosis of B-cell CLL, [[#Original_Rai_staging_.281975.29|Rai stage]] I through IV with evidence of progression according to the [[#NCI_Sponsored_International_Working_Group_Criteria_.281999.29|National Cancer Institute Working Group (NCI-WG) 1996 criteria]], no previous chemotherapy for CLL, a life expectancy of at least 12 weeks, [[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29|WHO performance status]] of 0 to 2, and adequate renal and liver function.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 40 mg/m<sup>2</sup> PO once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
−
'''28-day cycle for up to 12 cycles'''
+
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
−
 
 
===References===
 
===References===
−
# Ezdinli EZ, Stutzman L. Chlorambucil therapy for lymphomas and chronic lymphocytic leukemia. JAMA. 1965 Feb 8;191:444-50. [https://doi.org/10.1001/jama.1965.03080060018003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14238023 PubMed]
+
# Robert F, Omura GA, Birch R, Krauss S, Oldham R; SECG. Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial. J Clin Oncol. 1984 May;2(5):391-5. [https://doi.org/10.1200/jco.1984.2.5.391 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6374050/ PubMed]
−
# '''FRE-CLL-80:''' Binet JL, Chastang C, Dighiero G, Travad P; French Cooperative Group on Chronic Lymphocytic Leukaemia. Effectiveness of "CHOP" regimen in advanced untreated chronic lymphocytic leukaemia. Lancet. 1986 Jun 14;1(8494):1346-9. [https://doi.org/10.1016/S0140-6736(86)91663-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2872470 PubMed]
+
# '''SWOG S8012:''' Miller TP, Chen TT, Coltman CA Jr, O'Bryan RM, Vance RB, Weiss GB, Fletcher WS, Stephens RL, Livingston RB. Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung: a Southwest Oncology Group Study. J Clin Oncol. 1986 Apr;4(4):502-8. [https://doi.org/10.1200/JCO.1986.4.4.502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3007683 PubMed]
−
# '''FRE-CLL-85:''' Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet JL, Travade P; French Cooperative Group on Chronic Lymphocytic Leukemia. Chlorambucil in indolent chronic lymphocytic leukemia. N Engl J Med. 1998 May 21;338(21):1506-14. [https://doi.org/10.1056/NEJM199805213382104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9593789 PubMed]
+
==Carboplatin & Cisplatin {{#subobject:a0e2a9|Regimen=1}}==
−
# '''CALGB 9011:''' Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [https://doi.org/10.1056/NEJM200012143432402 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11114313 PubMed]
+
CC: '''<u>C</u>'''isplatin & '''<u>C</u>'''arboplatin
−
# '''LRF CLL4:''' Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-9. [https://doi.org/10.1016/S0140-6736(07)61125-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17658394 PubMed] NCT00004218
 
−
## '''Update:''' Else M, Wade R, Oscier D, Catovsky D. The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years. Br J Haematol. 2016 Jan;172(2):228-37. Epub 2015 Oct 12. [https://doi.org/10.1111/bjh.13824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832371/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26457986 PubMed]
 
−
# '''CAM 307:''' Hillmen P, Skotnicki AB, Robak T, Jaksic B, Dmoszynska A, Wu J, Sirard C, Mayer J. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007 Dec 10;25(35):5616-23. Epub 2007 Nov 5. [https://doi.org/10.1200/jco.2007.12.9098 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17984186 PubMed] NCT00046683
 
−
<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 6-9, 2008, and San Francisco, CA, December 8-11, 2007. -->
 
−
# Knauf WU, Lissichkov T, Aldaoud A, Liberati A, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Tremmel L, Merkle K, Montillo M. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol. 2009 Sep 10;27(26):4378-84. Epub 2009 Aug 3. [https://doi.org/10.1200/jco.2008.20.8389 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19652068 PubMed]
 
−
## '''Update:''' Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM, Loscertales J, Herbrecht R, Juliusson G, Postner G, Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet F, Del Giudice I, Klein P, Merkle K, Montillo M. Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukaemia: updated results of a randomized phase III trial. Br J Haematol. 2012 Oct;159(1):67-77. Epub 2012 Aug 4. [https://doi.org/10.1111/bjh.12000 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22861163 PubMed]
 
−
<!-- Results from an interim analysis were presented, in part, at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003. Preliminary results from the final analysis were presented, in part, at the 14th International CLL Workshop, London, United Kingdom, September 14-16, 2007, as well as at the 49th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007. -->
 
−
# '''GCLLSG CLL5:''' Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhöfer N, Rohrberg R, Söling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Döhner H, Emmerich B, Hallek M; German CLL Study Group. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15;114(16):3382-91. Epub 2009 Jul 15. [http://www.bloodjournal.org/content/114/16/3382.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19605849 PubMed] NCT00262795
 
−
<!-- # '''Abstract:''' Valentin Goede, Kirsten Fischer, Kathryn Humphrey, Elina Asikanius, Raymonde Busch, Anja Engelke, Clemens M. Wendtner, Olga Samoylova, Tatiana Chagorova, Marie-Sarah Dilhuydy, Javier De La Serna Torroba, Thomas Illmer, Stephen Opat, Carolyn Owen, Karl A Kreuzer, Anton W Langerak, Matthias Ritgen, Stephan Stilgenbauer, Michael Wenger, Michael Hallek; German CLL Study Group. Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial. J Clin Oncol 31, 2013 (suppl; abstr 7004) [http://meetinglibrary.asco.org/content/116249-132 link to abstract] -->
 
−
# '''GCLLSG CLL11:''' Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Döhner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20;370(12):1101-10. Epub 2014 Jan 8. [https://doi.org/10.1056/NEJMoa1313984 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24401022 PubMed] NCT01010061
 
−
## '''Update:''' Goede V, Fischer K, Engelke A, Schlag R, Lepretre S, Casado Montero LF, Montillo M, Fegan C, Asikanius E, Humphrey K, Fingerle-Rowson G, Hallek M. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia. 2015 Jul;29(7):1602-4. Epub 2015 Jan 30. [https://doi.org/10.1038/leu.2015.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25634683 PubMed]
 
−
<!-- # '''Abstract:''' Hillmen P, Tadeusz R, Janssens A, Govindbabu K, Grosicki S, Mayer J, Panagiotidis P, Kimby E, Schuh A, Boyd T, Montillo M, McKeown A, Carey J, Gupta I, Chang C, Lisby S, Offner F. Ofatumumab + Chlorambucil Versus Chlorambucil Alone In Patients With Untreated Chronic Lymphocytic Leukemia (CLL): Results Of The Phase III Study Complement 1 (OMB110911). ASH 2013 Annual Meeting abstract 528. [https://ash.confex.com/ash/2013/webprogram/Paper58498.html link to abstract] -->
 
−
# '''COMPLEMENT 1:''' Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, Pettitt AR, Boyd T, Montillo M, Gupta IV, Wright O, Dixon I, Carey JL, Chang CN, Lisby S, McKeown A, Offner F; COMPLEMENT 1 Study Investigators. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. 2015 May 9;385(9980):1873-83. Epub 2015 Apr 13. [https://doi.org/10.1016/S0140-6736(15)60027-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25882396 PubMed] NCT00748189
 
−
## '''Update:''' Offner F, Robak T, Janssens A, Govind Babu K, Kloczko J, Grosicki S, Mayer J, Panagiotidis P, Schuh A, Pettitt A, Montillo M, Werner O, Vincent G, Khanna S, Hillmen P. A five-year follow-up of untreated patients with chronic lymphocytic leukaemia treated with ofatumumab and chlorambucil: final analysis of the Complement 1 phase 3 trial. Br J Haematol. 2020 Sep;190(5):736-740. Epub 2020 Mar 31. [https://doi.org/10.1111/bjh.16625 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32236950 PubMed]
 
−
# '''RESONATE-2:''' Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, Bairey O, Hillmen P, Bartlett NL, Li J, Simpson D, Grosicki S, Devereux S, McCarthy H, Coutre S, Quach H, Gaidano G, Maslyak Z, Stevens DA, Janssens A, Offner F, Mayer J, O'Dwyer M, Hellmann A, Schuh A, Siddiqi T, Polliack A, Tam CS, Suri D, Cheng M, Clow F, Styles L, James DF, Kipps TJ; RESONATE-2 Investigators. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015 Dec 17;373(25):2425-37. Epub 2015 Dec 6. [https://doi.org/10.1056/NEJMoa1509388 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4722809/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26639149 PubMed] NCT01722487
 
−
## '''Update:''' Barr PM, Robak T, Owen C, Tedeschi A, Bairey O, Bartlett NL, Burger JA, Hillmen P, Coutre S, Devereux S, Grosicki S, McCarthy H, Li J, Simpson D, Offner F, Moreno C, Zhou C, Styles L, James D, Kipps TJ, Ghia P. Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2. Haematologica. 2018 Sep;103(9):1502-1510. Epub 2018 Jun 7. [http://www.haematologica.org/content/103/9/1502 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6119145/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29880603 PubMed]
 
−
## '''Update:''' Burger JA, Barr PM, Robak T, Owen C, Ghia P, Tedeschi A, Bairey O, Hillmen P, Coutre SE, Devereux S, Grosicki S, McCarthy H, Simpson D, Offner F, Moreno C, Dai S, Lal I, Dean JP, Kipps TJ. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020 Mar;34(3):787-798. Epub 2019 Oct 18. [https://doi.org/10.1038/s41375-019-0602-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/31628428 PubMed]
 
−
# '''ORIGIN:''' Chanan-Khan A, Egyed M, Robak T, Martinelli de Oliveira FA, Echeveste MA, Dolan S, Desjardins P, Blonski JZ, Mei J, Golany N, Zhang J, Gribben JG. Randomized phase 3 study of lenalidomide versus chlorambucil as first-line therapy for older patients with chronic lymphocytic leukemia (the ORIGIN trial). Leukemia. 2017 May;31(5):1240-1243. Epub 2017 Jan 31. [https://www.nature.com/articles/leu201747 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420789/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28140392 PubMed] NCT00910910
 
−
==Chlorambucil & Prednisone {{#subobject:f03d93|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 0.3/40 {{#subobject:157c8a|Variant=1}}===
+
===Regimen {{#subobject:e1bc46|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 297: Line 278:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM199805213382104 Dighiero et al. 1998 (FRE-CLL-85)]
+
|[https://doi.org/10.1200/JCO.1998.16.4.1388 Sculier et al. 1998]
−
|1985-1990
+
|1990-1995
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#Observation|Observation]]
+
|[[#CCI|CCI]]
−
|style="background-color:#1a9850"|Superior PFS
+
| style="background-color:#d73027" |Inferior ORR
 
|-
 
|-
 
|}
 
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 0.3 mg/kg PO once per day on days 1 to 5
+
*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup> IV once on day 1
−
====Glucocorticoid therapy====
+
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 2 & 3
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
</div></div>
−
'''1-month cycle for up to 36 cycles (3 years)'''
+
===References===
−
</div></div><br>
+
# Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. [https://doi.org/10.1200/JCO.1998.16.4.1388 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9552042 PubMed]
 +
==CCI {{#subobject:a0532c|Regimen=1}}==
 +
CCI: '''<u>C</u>'''isplatin, '''<u>C</u>'''arboplatin, '''<u>I</u>'''fosfamide
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 12/30 {{#subobject:6ce9db|Variant=1}}===
+
===Regimen {{#subobject:ebjb16|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 320: Line 304:
 
!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/96/8/2723 Robak et al. 2000 (PALG CLL1)]
+
|[https://doi.org/10.1200/JCO.1998.16.4.1388 Sculier et al. 1998]
−
|1995-1998
+
|1990-1995
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[#Carboplatin_.26_Cisplatin|CC]]
 +
| style="background-color:#1a9850" |Superior ORR
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdf154 Sculier et al. 2002]
 +
|1998-2000
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Cladribine_.26_Prednisone_88|Cladribine & Prednisone]]
+
|1. [[Stub#CCG|CCG]]<br>2. [[#Ifosfamide_.26_Gemcitabine|IG]]
−
| style="background-color:#d73027" |Inferior ORR
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 12 mg/m<sup>2</sup> PO once per day on days 1 to 7
+
*[[Carboplatin (Paraplatin)]]
−
====Glucocorticoid therapy====
+
*[[Cisplatin (Platinol)]]
−
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup> PO once per day on days 1 to 7
+
*[[Ifosfamide (Ifex)]]
−
'''28-day cycles, continued until CR'''
+
</div></div>
−
</div></div><br>
+
===References===
 +
# Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. [https://doi.org/10.1200/JCO.1998.16.4.1388 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9552042 PubMed]
 +
# Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. [https://doi.org/10.1093/annonc/mdf154 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12123332 PubMed]
 +
==Cisplatin monotherapy {{#subobject:a0eb49|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, 30/80 {{#subobject:213140|Variant=1}}===
+
===Regimen {{#subobject:e32b46|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 343: Line 336:
 
!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.1991.9.5.770 Raphael et al. 1991 (ECOG E2480)]
+
|[https://doi.org/10.1200/JCO.1993.11.5.873 Gandara et al. 1993]
 +
|1988-1990
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[#Cisplatin_monotherapy_99|HDCP]]<br>2. [[#Cisplatin_.26_Mitomycin_99|HDCP-M]]
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.6.1351 von Pawel et al. 2000 (CATAPULT I)]
 
|NR
 
|NR
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#CVP|CVP]]
+
|[[#Cisplatin_.26_Tirapazamine_77|Cisplatin & Tirapazamine]]
−
|style="background-color:#ffffbf"|Did not meet efficacy endpoints
+
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.19.3390 Gatzemeier et al. 2000]
 +
|1995-1996
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 +
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
|-
 
|-
 
|}
 
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Chlorambucil (Leukeran)]] 30 mg/m<sup>2</sup> PO once on day 1
+
*[[Cisplatin (Platinol)]]
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 80 mg PO once per day on days 1 to 5
 
−
'''14-day cycle for up to 39 cycles (18 months)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Raphael BG, Silber R, Moore DF, et al: Survival duration and complete remission (CR) incidence in advanced chronic lymphocytic leukemia (CLL). Blood 67: 229A, 1986 -->
+
# Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, Neefe JR, Hutchins LF, Roach RW, Grunberg SM, Braun TJ, Natale RB, Balcerzak SP; [[Study_Groups#SWOG|SWOG]]. Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol. 1993 May;11(5):873-8. [https://doi.org/10.1200/JCO.1993.11.5.873 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8387576 PubMed]
−
# '''ECOG E2480:''' Raphael B, Andersen JW, Silber R, Oken M, Moore D, Bennett J, Bonner H, Hahn R, Knospe WH, Mazza J, Glick J. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol. 1991 May;9(5):770-6. [https://doi.org/10.1200/jco.1991.9.5.770 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2016618 PubMed]
+
# '''CATAPULT I:''' von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, Talbot D, Rey A, Butler TW, Hirsh V, Olver I, Bergman B, Ayoub J, Richardson G, Dunlop D, Arcenas A, Vescio R, Viallet J, Treat J. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group: cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J Clin Oncol. 2000 Mar;18(6):1351-9. [https://doi.org/10.1200/JCO.2000.18.6.1351 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10715308 PubMed]
−
# '''FRE-CLL-85:''' Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet JL, Travade P. Chlorambucil in indolent chronic lymphocytic leukemia: French Cooperative Group on Chronic Lymphocytic Leukemia. N Engl J Med. 1998 May 21;338(21):1506-14. [https://doi.org/10.1056/NEJM199805213382104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9593789 PubMed]
+
# Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. [https://doi.org/10.1200/JCO.2000.18.19.3390 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11013280 PubMed]
−
# '''PALG CLL1:''' Robak T, Bloński JZ, Kasznicki M, Blasińska-Morawiec M, Krykowski E, Dmoszyńska A, Mrugala-Spiewak H, Skotnicki AB, Nowak W, Konopka L, Ceglarek B, Maj S, Dwilewicz-Trojaczek J, Hellmann A, Urasiński I, Zdziarska B, Kotlarek-Haus S, Potoczek S, Grieb P. Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial. Blood. 2000 Oct 15;96(8):2723-9. [http://www.bloodjournal.org/content/96/8/2723 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11023504 PubMed]
+
==Cisplatin & Pemetrexed {{#subobject:af12b4|Regimen=1}}==
−
==CHOP {{#subobject:3b1abe|Regimen=1}}==
+
Pem-Cis: '''<u>Pem</u>'''etrexed & '''<u>Cis</u>'''platin
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
<br>Cis-Pem: '''<u>Cis</u>'''platin & '''<u>Pem</u>'''etrexed
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:557db6|Variant=1}}===
+
===Regimen {{#subobject:8fdaa3|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 373: Line 376:
 
!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/S0140-6736(86)91663-6 Binet et al. 1986 (FRE-CLL-80)]
+
|[https://doi.org/10.1200/jco.2007.15.0375 Scagliotti et al. 2008 (JMDB)]
−
|1980-1985
+
|2004-2005
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
−
|[[#CVP|CVP]]
+
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
−
|style="background-color:#1a9850"|Superior OS
+
|style="background-color:#eeee01"|Seems to have non-inferior OS
−
|-
 
−
|rowspan=2|[http://www.bloodjournal.org/content/98/8/2319.long Leporrier et al. 2001 (FCGCLL 1996)]
 
−
|rowspan=2|1990-1998
 
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#CAP|CAP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Fludarabine_monotherapy|Fludarabine]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: although this regimen is still current for nonsquamous NSCLC, the JMDB trial was unselected by histology.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1, '''given second'''
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
+
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
−
*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> IV once on day 1
+
====Supportive therapy====
−
====Glucocorticoid therapy====
+
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to [[Pemetrexed (Alimta)]]
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*Folic acid 1 mg PO once per day
−
'''28-day cycle for 6 cycles'''
+
*In Sequist et al. 2013: Patients "received folic acid, vitamin B12, and dexamethasone, as per package recommendations for [[Pemetrexed (Alimta)]]."
 +
'''21-day cycle for 4 to 6 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''FRE-CLL-80:''' Binet JL, Chastang C, Dighiero G, Travad P; French Cooperative Group on Chronic Lymphocytic Leukaemia. Effectiveness of "CHOP" regimen in advanced untreated chronic lymphocytic leukaemia. Lancet. 1986 Jun 14;1(8494):1346-9. [https://doi.org/10.1016/S0140-6736(86)91663-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2872470 PubMed]
+
# '''JMDB:''' Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [https://doi.org/10.1200/jco.2007.15.0375 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18506025 PubMed]
−
## '''Update:''' Benichou J, Binet JL, Chastang C, Chevret S, Dighiero G, Travade P; French Cooperative Group on Chronic Lymphocytic Leukaemia. Long-term results of the CHOP regimen in stage C chronic lymphocytic leukaemia. Br J Haematol. 1989 Nov;73(3):334-40. [https://doi.org/10.1111/j.1365-2141.1989.tb07749.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/2690923 PubMed]
+
==Cisplatin & Vinblastine {{#subobject:2fe6d3|Regimen=1}}==
−
# '''FCGCLL 1996:''' Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C; French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001 Oct 15;98(8):2319-25. [http://www.bloodjournal.org/content/98/8/2319.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11588025 PubMed]
+
VP: '''<u>V</u>'''inblastine & '''<u>P</u>'''latinol (Cisplatin)
−
==CMC {{#subobject:25f5b2|Regimen=1}}==
 
−
CMC: '''<u>C</u>'''ladribine, '''<u>M</u>'''itoxantrone, '''<u>C</u>'''yclophosphamide
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:c2431|Variant=1}}===
+
===Regimen {{#subobject:c5e07c|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 413: Line 407:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|rowspan=2|[http://www.bloodjournal.org/content/108/2/473.long Robak et al. 2006 (PALG CLL2)]
+
|[https://doi.org/10.1200/JCO.1994.12.6.1113 Kosty et al. 1994 (CALGB 8931)]
−
|rowspan=2|1998-2003
+
|1989-1991
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|1. [[Chronic_lymphocytic_leukemia#Cladribine_monotherapy|Cladribine]]
+
|[[#Cisplatin.2C_Hydrazine.2C_Vinblastine_77|VP & Hydrazine]]
−
|style="background-color:#1a9850"|Superior CR rate
+
|style="background-color:#ffffbf"|Seems not superior
−
|-
 
−
|2. [[Chronic_lymphocytic_leukemia#Cladribine_.26_Cyclophosphamide_.28CC.29|CC]]
 
−
|style="background-color:#91cf60"|Seems to have superior CR rate
 
 
|-
 
|-
 
|}
 
|}
 
<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 3
+
*[[Cisplatin (Platinol)]]
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
+
*[[Vinblastine (Velban)]]  
−
*[[Cyclophosphamide (Cytoxan)]] 650 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Preliminary results of this study were presented at the 44th Annual Meeting of the American Society of Hematology, Philadelphia, PA, December 6-10, 2002; and at the 10th International Workshop on CLL, Stresa, Lake Maggiore, Italy, October 10-12, 2003; and at the 46th Annual Meeting of the American Society of Hematology, San Diego, CA, December 4-7, 2004; and at the 11th International Workshop on CLL, New York, NY, September 16-18, 2005. -->
+
# '''CALGB 8931:''' Kosty MP, Fleishman SB, Herndon JE 2nd, Coughlin K, Kornblith AB, Scalzo A, Morris JC, Mortimer J, Green MR; [[Study_Groups#CALGB|CALGB]]. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1994 Jun;12(6):1113-20. [https://doi.org/10.1200/JCO.1994.12.6.1113 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8201372 PubMed]
−
# '''PALG CLL2:''' Robak T, Blonski JZ, Gora-Tybor J, Jamroziak K, Dwilewicz-Trojaczek J, Tomaszewska A, Konopka L, Ceglarek B, Dmoszynska A, Kowal M, Kloczko J, Stella-Holowiecka B, Sulek K, Calbecka M, Zawilska K, Kuliczkowski K, Skotnicki AB, Warzocha K, Kasznicki M; Polish Adult Leukemia Group. Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2). Blood. 2006 Jul 15;108(2):473-9. Epub 2006 Mar 21. [http://www.bloodjournal.org/content/108/2/473.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16551966 PubMed]
+
==Cisplatin & Vindesine {{#subobject:80fe2|Regimen=1}}==
−
==CVP {{#subobject:c1b3ad|Regimen=1}}==
+
VP: '''<u>V</u>'''indesine & '''<u>P</u>'''latinol (Cisplatin)
−
CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
+
<br>VdsC: '''<u>V</u>'''in'''<u>d</u>'''e'''<u>s</u>'''ine & '''<u>C</u>'''isplatin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, PO cyclophosphamide; uncapped vincristine {{#subobject:88f0a5|Variant=1}}===
+
===Regimen {{#subobject:2d16cd|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 444: Line 433:
 
!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.1991.9.5.770 Raphael et al. 1991 (ECOG E2480)]
+
|[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
−
|NR
+
|1981-1983
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
−
|[[#Chlorambucil_.26_Prednisone|Chlorambucil & Prednisone]]
+
|1. [[Non-small_cell_lung_cancer_-_historical#CAMP|CAMP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29|EC]]<br> 3. [[#MVP_.28Vinblastine.29|MVP]]
−
|style="background-color:#ffffbf"|Did not meet efficacy endpoints
+
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.1988.6.4.633 Rapp et al. 1988]
 +
|1983-1986
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[#Best_supportive_care|Best supportive care]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|[https://doi.org/10.1111/j.1440-1843.1996.tb00010.x Masutani et al. 1999]
 +
|1987-1992
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[Stub#PVI|PVI]]<br>2. [[#MVP_.28Vindesine.29|PVM]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1016/s0169-5002(02)00008-9 Kodani et al. 2002]
 +
|1987-1992
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#PVI|PVI]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ Negoro et al. 2003]
 +
|1995-1998
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1023/a:1012208711013 Vansteenkiste et al. 2001]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|1996-1999
−
====Chemotherapy====
+
|style="background-color:#1a9851"|Phase 3 (C)
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
|[[#Gemcitabine_monotherapy|Gemcitabine]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
+
| style="background-color:#fc8d59" |Seems to have inferior clinical benefit
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for up to 26 cycles (18 months)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, capped vincristine {{#subobject:14a751|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/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
+
|[https://doi.org/10.1200/JCO.2004.06.114 Kubota et al. 2004]
−
|NR
+
|1998-2000
−
|style="background-color:#91cf61"|Non-randomized portion of phase 3 RCT
+
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+
*[[Cisplatin (Platinol)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Vindesine (Eldisine)]]  
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Rituximab_monotherapy_2|Rituximab]] maintenance versus [[#Observation_2|observation]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Raphael BG, Silber R, Moore DF, et al: Survival duration and complete remission (CR) incidence in advanced chronic lymphocytic leukemia (CLL). Blood 67: 229A, 1986 -->
+
# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
−
# '''ECOG E2480:''' Raphael B, Andersen JW, Silber R, Oken M, Moore D, Bennett J, Bonner H, Hahn R, Knospe WH, Mazza J, Glick J. Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial. J Clin Oncol. 1991 May;9(5):770-6. [https://doi.org/10.1200/jco.1991.9.5.770 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2016618 PubMed]
+
# Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. [https://doi.org/10.1200/JCO.1988.6.4.633 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2833577 PubMed]
−
# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed] NCT00003204
+
# Masutani M, Akusawa H, Kadota A, Ohchi Y, Takahashi N, Tanigawa S, Koya Y, Horie T. A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer. Respirology. 1996 Mar;1(1):49-54. [https://doi.org/10.1111/j.1440-1843.1996.tb00010.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/9432405 PubMed]
−
==FC {{#subobject:42f3ac|Regimen=1}}==
+
# Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. [https://doi.org/10.1023/a:1012208711013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11697832 PubMed]
−
FC: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide
+
# Kodani T, Ueoka H, Kiura K, Tabata M, Takigawa N, Segawa Y, Moritaka T, Hiraki S, Harada M, Tanimoto M. A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors. Lung Cancer. 2002 Jun;36(3):313-9. [https://doi.org/10.1016/s0169-5002(02)00008-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12009244 PubMed]
 +
# Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. [https://doi.org/10.1038/sj.bjc.6600725 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12569373 PubMed]
 +
# Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. [https://doi.org/10.1200/JCO.2004.06.114 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14722033 PubMed]
 +
==Docetaxel monotherapy {{#subobject:ec36b5|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 75/750 (IV fludarabine) {{#subobject:ad1330|Variant=1}}===
+
===Regimen {{#subobject:dd8369|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 498: Line 499:
 
!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/10.1016/S0140-6736(07)61125-8 Catovsky et al. 2007 (LRF CLL4)]
+
|[https://doi.org/10.1016/s0169-5002(00)00094-5 Roszkowski et al. 2000]
−
|rowspan=2|1999-2004
+
|1995-NR
−
|rowspan = "2" style="background-color:#1a9851"|Phase 3 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]
+
|[[#Best_supportive_care|Best supportive care]]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+
| style="background-color:#91cf60" |Seems to have superior OS
−
|-
 
−
|2. [[#Fludarabine_monotherapy|Fludarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(10)61381-5 Hallek et al. 2010 (GCLLSG CLL8)]
+
|[https://doi.org/10.1016/j.lungcan.2007.07.021 Georgoulias et al. 2007]
−
|2003-2006
+
|2002-2004
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#FCR|FCR]]
+
|[[#Docetaxel_.26_Gemcitabine|DG]]
−
|style="background-color:#d73027"|Inferior OS<sup>1</sup>
+
| style="background-color:#fc8d59" |Seems to have inferior OS
−
|-
 
−
|[https://doi.org/10.1200/jco.2009.25.9630 Robak et al. 2010 (PALG-CLL3)]
 
−
|2004-2007
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[Chronic_lymphocytic_leukemia#Cladribine_.26_Cyclophosphamide_.28CC.29|CC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy for GCLLSG CLL8 is based on the updated 2016 results.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
*[[Docetaxel (Taxotere)]]
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 to 3
+
</div></div>
−
====Supportive therapy====
+
===References===
−
*Per '''Robak et al. 2010''': "No routine prophylaxis with antibiotics, antiviral agents, or growth factors."
+
# Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, Parisi A, Pham Tran N, Olivares R, Berille J. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer. 2000 Mar;27(3):145-57. [https://doi.org/10.1016/s0169-5002(00)00094-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10699688 PubMed]
−
'''28-day cycle for up to 6 cycles'''
+
# Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. [https://doi.org/10.1016/j.lungcan.2007.07.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17765354 PubMed]
−
</div></div><br>
+
==Docetaxel & Gemcitabine {{#subobject:80fe2|Regimen=1}}==
 +
DG: '''<u>D</u>'''ocetaxel & '''<u>G</u>'''emcitabine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 90/750 {{#subobject:c2ddf9|Variant=1}}===
+
===Regimen {{#subobject:2d16cd|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 17%"|Study
+
!style="width: 20%"|Study
−
!style="width: 15%"|Years of enrollment
+
!style="width: 20%"|Years of enrollment
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 17%"|Comparator
+
!style="width: 20%"|Comparator
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/107/3/885.long Eichhorst et al. 2005 (GCLLSG CLL4)]
+
|[https://doi.org/10.1016/j.lungcan.2007.07.021 Georgoulias et al. 2007]
−
|1999-2003
+
|2002-2004
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#Fludarabine_monotherapy|Fludarabine]]
+
|[[#Docetaxel_monotherapy|Docetaxel]]
−
|style="background-color:#1a9850"|Superior PFS
+
| style="background-color:#91cf60" |Seems to have superior OS
−
|style="background-color:#ffffbf"|No statistical difference in HRQoL
 
 
|-
 
|-
 
|}
 
|}
 +
''Note: while this is a superior arm of a phase III RCT, the comparator (single-agent docetaxel) is not usually used in the first-line treatment and this regimen is not currently recommended by ESMO guidelines.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
+
*[[Docetaxel (Taxotere)]]
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
+
*[[Gemcitabine (Gemzar)]]  
−
====Supportive therapy====
+
</div></div>
−
*No routine antibiotic, antiviral, or growth factor use
+
===References===
−
'''28-day cycle for up to 6 cycles'''
+
# Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. [https://doi.org/10.1016/j.lungcan.2007.07.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17765354 PubMed]
−
</div></div><br>
+
==Ifosfamide & Gemcitabine {{#subobject:80fe2|Regimen=1}}==
 +
IG: '''<u>I</u>'''fosfamide & '''<u>G</u>'''emcitabine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, 100/600 {{#subobject:447aa0|Variant=1}}===
+
===Regimen {{#subobject:2d16cd|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 564: Line 556:
 
!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.2006.08.0762 Flinn et al. 2007 (ECOG E2997)]
+
|[https://doi.org/10.1093/annonc/mdf154 Sculier et al. 2002]
−
|1999-NR
+
|1998-2000
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#Fludarabine_monotherapy|Fludarabine]]
+
|1. [[#CCI|CCI]]<br>2. [[Stub#CCG|CCG]]
−
|style="background-color:#1a9850"|Superior PFS
+
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[http://ar.iiarjournals.org/content/33/12/5477.long Berghmans et al. 2013 (ELCWP-01041)]
 +
|2003-2009
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[#GIP|GIP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|DP]]
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen was intended for untreated patients greater than or equal to 18 years with a diagnosis of progressive CLL using the [[#NCI_Sponsored_Working_Group_Criteria_.281996.29|National Cancer Institute criteria]].''
+
''Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Ifosfamide (Ifex)]]
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
+
*[[Gemcitabine (Gemzar)]]  
−
'''28-day cycle for up to 6 cycles'''
+
</div></div>
−
</div></div><br>
+
===References===
 +
# Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. [https://doi.org/10.1093/annonc/mdf154 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12123332 PubMed]
 +
# '''ELCWP-01041:''' Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. [http://ar.iiarjournals.org/content/33/12/5477.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/24324084 PubMed] NCT00622349
 +
==Gemcitabine monotherapy {{#subobject:826de2|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #4, 120/750 (PO fludarabine) {{#subobject:20616|Variant=1}}===
+
===Regimen {{#subobject:4b26cd|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 587: Line 588:
 
!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/123/21/3255.long Geisler et al. 2014 (HOVON-68)]
+
|[https://doi.org/10.1023/a:1012208711013 Vansteenkiste et al. 2001]
−
|2006-2010
+
|1996-1999
 +
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 +
|[[#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]
 +
| style="background-color:#91cf60" |Seems to have superior clinical benefit
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.01.2781 Sederholm et al. 2005]
 +
|1998-2001
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#FCA|FCA]]
+
|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]
−
|style="background-color:#d73027"|Inferior PFS
+
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|}
 +
''Note: this regimen is considered current in elderly patients or those with poor PS; these trials were unselected by these parameters.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]]
 +
</div></div>
 +
===References===
 +
# Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. [https://doi.org/10.1023/a:1012208711013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11697832 PubMed]
 +
# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [https://doi.org/10.1200/jco.2005.01.2781 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16293868 PubMed]
 +
==GIP {{#subobject:2c098d|Regimen=1}}==
 +
GIP: '''<u>G</u>'''emcitabine, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:9a4cf6|Variant=1}}===
 +
{| class="wikitable" 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/10.1093/annonc/mdm084 Sculier et al. 2007]
 +
|2000-2004
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen was intended for patients with previously untreated CLL diagnosed and in need of treatment according to the [[#NCI_Sponsored_Working_Group_Criteria_.281996.29|National Cancer Institute guidelines]], 18 to 75 years of age, with [[Performance_status#ECOG_performance_status_.28WHO.2FZubrod_score.29|WHO performance status]] less than 3 and no severe comorbidities, with high-risk CLL as defined by the presence of either unmutated IGHV, [[#Risk_by_FISH_.282000.29|17p deletion, 11q deletion, or trisomy 12 by FISH]].''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 3
+
*[[Gemcitabine (Gemzar)]]
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> PO once per day on days 1 to 3
+
*[[Ifosfamide (Ifex)]]
−
====Supportive therapy====
+
*[[Cisplatin (Platinol)]]
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS) | Cotrimoxazole]] 400/80 mg PO once per day until 6 months after end of treatment
+
</div></div>
−
*One of the following:
+
===References===
−
**[[Acyclovir (Zovirax)]] 400 mg PO three times per day until 3 months after end of treatment
+
# Sculier JP, Lafitte JJ, Lecomte J, Alexopoulos CG, Van Cutsem O, Giner V, Efremidis A, Berchier MC, Collon T, Meert AP, Scherpereel A, Ninane V, Paesmans M, Berghmans T; European Lung Cancer Working Party. A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer. Ann Oncol. 2007 Jun;18(6):1037-42. Epub 2007 Apr 2. [https://doi.org/10.1093/annonc/mdm084 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17404152 PubMed]
−
**[[Valacyclovir (Valtrex)]] 500 mg PO twice per day until 3 months after end of treatment
+
==MACC {{#subobject:3f2f0c|Regimen=1}}==
−
'''28-day cycle for 6 cycles'''
+
MACC: '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>C</u>'''CNU (Lomustine)
−
</div></div><br>
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #5, 120/750 (all PO) {{#subobject:470e55|Variant=1}}===
+
===Regimen {{#subobject:cec9d6|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 615: Line 642:
 
!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/10.1016/S0140-6736(07)61125-8 Catovsky et al. 2007 (LRF CLL4)]
+
|[https://jamanetwork.com/journals/jama/article-abstract/353407 Chahinian et al. 1977]
−
|rowspan=2|1999-2004
+
|NR
−
|rowspan = "2" style="background-color:#1a9851"|Phase 3 (E-esc)
+
| style="background-color:#91cf61" |Non-randomized
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]
+
| style="background-color:#d3d3d3" |
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|2. [[#Fludarabine_monotherapy|Fludarabine]]
+
|[https://doi.org/10.1002/1097-0142(19820901)50:5%3C845::AID-CNCR2820500507%3E3.0.CO;2-S Cormier et al. 1982]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+
|NR
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[#Placebo|Placebo]]
 +
|style="background-color:#1a9850"|Superior OS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 24 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Methotrexate (MTX)]]
−
*[[Cyclophosphamide (Cytoxan)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Doxorubicin (Adriamycin)]]
−
'''28-day cycle for up to 6 cycles'''
+
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Lomustine (CCNU)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GCLLSG CLL4:''' Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jäger U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Döhner H, Brittinger G, Emmerich B, Hallek M; German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006 Feb 1;107(3):885-91. Epub 2005 Oct 11. [http://www.bloodjournal.org/content/107/3/885.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16219797 PubMed] NCT00276848
+
# Chahinian PA, Arnold DJ, Cohen JM, Purpora DP, Jaffrey IS, Teirstein AS, Kirschner PA, Holland JF. Chemotherapy for bronchogenic carcinoma: methotrexate, doxorubicin, cyclophosphamide, and lomustine. JAMA. 1977 May 30;237(22):2392-6. [https://jamanetwork.com/journals/jama/article-abstract/353407 link to original article] [https://pubmed.ncbi.nlm.nih.gov/576939 PubMed]
−
## '''HRQoL analysis:''' Eichhorst BF, Busch R, Obwandner T, Kuhn-Hallek I, Herschbach P, Hallek M; German CLL Study Group. Health-related quality of life in younger patients with chronic lymphocytic leukemia treated with fludarabine plus cyclophosphamide or fludarabine alone for first-line therapy: a study by the German CLL Study Group. J Clin Oncol. 2007 May 1;25(13):1722-31. Epub 2007 Mar 26. [https://doi.org/10.1200/JCO.2006.05.6929 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17389338 PubMed]
+
# Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. [https://doi.org/10.1002/1097-0142(19820901)50:5%3C845::AID-CNCR2820500507%3E3.0.CO;2-S link to original article] [https://pubmed.ncbi.nlm.nih.gov/7093924 PubMed]
−
<!-- Presented in part at the 46th Annual Meeting of the American Society of Hematology, December 3-7, 2004, San Diego, CA. -->
+
==MIC {{#subobject:d1b4dd|Regimen=1}}==
−
# '''ECOG E2997:''' Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, Hussein MA, Appelbaum FR, Larson RA, Moore DF Jr, Tallman MS. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007 Mar 1;25(7):793-8. Epub 2007 Feb 5. [https://doi.org/10.1200/jco.2006.08.0762 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17283364 PubMed] NCT00003764
+
MIC: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>C</u>'''isplatin
−
## '''Update:''' Lucas DM, Ruppert AS, Lozanski G, Dewald GW, Lozanski A, Claus R, Plass C, Flinn IW, Neuberg DS, Paietta EM, Bennett JM, Jelinek DF, Gribben JG, Hussein MA, Appelbaum FR, Larson RA, Moore DF Jr, Tallman MS, Byrd JC, Grever MR. Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997. Leuk Lymphoma. 2015;56(11):3031-7. Epub 2015 Mar 30. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1023800 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688910/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25721902 PubMed]
+
<br>MIP: '''<u>M</u>'''itomycin, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
−
# '''LRF CLL4:''' Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-9. [https://doi.org/10.1016/S0140-6736(07)61125-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17658394 PubMed] NCT00004218
 
−
## '''Update:''' Else M, Wade R, Oscier D, Catovsky D. The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years. Br J Haematol. 2016 Jan;172(2):228-37. Epub 2015 Oct 12. [https://doi.org/10.1111/bjh.13824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832371/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26457986 PubMed]
 
−
<!-- Presented at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL; the 12th Congress of the European Hematology Association, June 7-10, 2007, Vienna, Austria; the XII International Workshop on Chronic Lymphocytic Leukemia, September 14-16, 2007, London, United Kingdom; the 49th Annual Meeting of the American Society of Hematology, December 8-11, 2007, Atlanta, GA; the 13th Congress of the European Hematology Association, June 12-15, 2008, Copenhagen, Denmark; and the 50th Annual Meeting of the American Society of Hematology, December 6-9, 2008, San Francisco, CA. -->
 
−
# '''PALG-CLL3:''' Robak T, Jamroziak K, Gora-Tybor J, Stella-Holowiecka B, Konopka L, Ceglarek B, Warzocha K, Seferynska I, Piszcz J, Calbecka M, Kostyra A, Dwilewicz-Trojaczek J, Dmoszyñska A, Zawilska K, Hellmann A, Zdunczyk A, Potoczek S, Piotrowska M, Lewandowski K, Blonski JZ; Polish Adult Leukemia Group. Comparison of cladribine plus cyclophosphamide with fludarabine plus cyclophosphamide as first-line therapy for chronic lymphocytic leukemia: a phase III randomized study by the Polish Adult Leukemia Group (PALG-CLL3 Study). J Clin Oncol. 2010 Apr 10;28(11):1863-9. Epub 2010 Mar 8. [https://doi.org/10.1200/jco.2009.25.9630 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20212251 PubMed]
 
−
# '''GCLLSG CLL8:''' Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010 Oct 2;376(9747):1164-74. [https://doi.org/10.1016/S0140-6736(10)61381-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20888994 PubMed] NCT00281918
 
−
## '''Update:''' Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, Langerbeins P, von Tresckow J, Engelke A, Maurer C, Kovacs G, Herling M, Tausch E, Kreuzer KA, Eichhorst B, Böttcher S, Seymour JF, Ghia P, Marlton P, Kneba M, Wendtner CM, Döhner H, Stilgenbauer S, Hallek M. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016 Jan 14;127(2):208-15. Epub 2015 Oct 20. [http://www.bloodjournal.org/content/127/2/208.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/26486789 PubMed]
 
−
## '''HRQoL analysis:''' Kutsch N, Busch R, Bahlo J, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Wendtner CM, Maria Fink A, Fischer K, Hallek M, Eichhorst B. FCR front-line therapy and quality of life in patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2017 Feb;58(2):399-407. Epub 2016 Jun 29. [https://doi.org/10.1080/10428194.2016.1190966 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27357445 PubMed]
 
−
<!-- Presented in abstract form at the 53rd annual meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011, and the XV International Workshop on CLL, Cologne, Germany, September 8-11, 2013. -->
 
−
# '''HOVON-68:''' Geisler CH, van T' Veer MB, Jurlander J, Walewski J, Tjønnfjord G, Itälä Remes M, Kimby E, Kozak T, Polliack A, Wu KL, Wittebol S, Abrahamse-Testroote MC, Doorduijn J, Ghidey Alemayehu W, van Oers MH. Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL. Blood. 2014 May 22;123(21):3255-62. Epub 2014 Apr 15. [http://www.bloodjournal.org/content/123/21/3255.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24735962 PubMed] NTR529
 
−
==FCM {{#subobject:f6adfc|Regimen=1}}==
 
−
FCM: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1 {{#subobject:e76bd1|Variant=1}}===
+
===Regimen {{#subobject:99a9f2|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 657: Line 677:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1111/j.1365-2141.2010.08317.x Hillmen et al. 2011 (NCRI CLL201)]
+
|[https://doi.org/10.1200/JCO.1999.17.10.3188 Cullen et al. 1999 (MIC2)]
−
|2005-2007
+
|1988-1996
−
|style="background-color:#1a9851"|Randomized Phase 2 (C)
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[Chronic_lymphocytic_leukemia_-_historical#R-FCM|FCM-R]]
+
|[[#Best_supportive_care|Best supportive care]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
+
|style="background-color:#91cf60"|Seems to have superior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.1999.17.11.3522 Crinò et al. 1999]
 +
|1995-1997
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#fc8d59" |Seems to have inferior ORR
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363584/ Sculier et al. 2000]
 +
|1995-1998
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#CarboMIP|CarboMIP]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1002/cncr.11535 Danson et al. 2003]
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+
|1997-2001
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|style="background-color:#1a9851"|Phase 3 (C)
−
====Chemotherapy====
+
|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|GC]]
−
*[[Fludarabine (Fludara)]] 24 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
|style="background-color:#ffffbf"|Seems not superior
−
*[[Cyclophosphamide (Cytoxan)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
*[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:455511|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/10.1158/1078-0432.CCR-07-1371 Bosch et al. 2008]
+
|[https://doi.org/10.1093/annonc/mdl078 Booton et al. 2006 (BTOG1)]
−
|2001-2004
+
|2001-2002
−
|style="background-color:#91cf61"|Phase 2
+
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer#Carboplatin_.26_Docetaxel|DCb]]
 +
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
+
*[[Mitomycin (Mutamycin)]]
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
+
*[[Ifosfamide (Ifex)]]
−
*[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+
*[[Cisplatin (Platinol)]]
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factor]] (type not specified) 300 mcg SC once per day on days 1 to 7
 
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 5
 
−
'''28-day cycle for 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Bosch F, Ferrer A, Villamor N, González M, Briones J, González-Barca E, Abella E, Gardella S, Escoda L, Pérez-Ceballos E, Asensi A, Sayas MJ, Font L, Altés A, Muntañola A, Bertazzoni P, Rozman M, Aymerich M, Giné E, Montserrat E. Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication. Clin Cancer Res. 2008 Jan 1;14(1):155-61. [https://doi.org/10.1158/1078-0432.CCR-07-1371 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172266 PubMed]
+
# '''MIC2:''' Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. [https://doi.org/10.1200/JCO.1999.17.10.3188 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10506617 PubMed]
−
<!--
+
# Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. [https://doi.org/10.1200/JCO.1999.17.11.3522 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10550150 PubMed]
−
# Hillmen P, Pocock C, Cohen D, Cocks K, Sayala HA, Rawstron A, et al. NCRI CLL201 trial: a randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated CLL. Blood 2007;110(11):752.
+
# Sculier JP, Lafitte JJ, Paesmans M, Thiriaux J, Alexopoulos CG, Baumöhl J, Schmerber J, Koumakis G, Florin MC, Zacharias C, Berghmans T, Mommen P, Ninane V, Klastersky J. Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer. Br J Cancer. 2000 Nov;83(9):1128-35. [https://doi.org/10.1054/bjoc.2000.1413 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363584/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11027424 PubMed]
−
# Hillmen P, Pocock C, Cohen D, Gregory W, Cocks K, Rawstron AC, et al. NCRI CLL201 Trial: a randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated CLL. British Journal of Haematology 2008;141(Suppl 1):119.
+
# Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://doi.org/10.1002/cncr.11535 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12879472 PubMed]
−
-->
+
# '''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599 PubMed]
−
# Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, Kennedy DB, Fegan C, Milligan DW, Radford J, Mercieca J, Dearden C, Ezekwisili R, Smith AF, Brown J, Booth GA, Varghese AM, Pocock C; NCRI CLL Sub-Group. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol. 2011 Mar;152(5):570-8. Epub 2011 Jan 14. [https://doi.org/10.1111/j.1365-2141.2010.08317.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21231927 PubMed]
+
==MVP (Vinblastine) {{#subobject:eb48eb|Regimen=1}}==
−
==Fludarabine monotherapy {{#subobject:aaed0b|Regimen=1}}==
+
MVP: '''<u>M</u>'''itomycin, '''<u>V</u>'''inblastine, '''<u>P</u>'''latinol (Cisplatin)
−
F: '''<u>F</u>'''ludarabine
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, IV {{#subobject:63d019|Variant=1}}===
+
===Regimen {{#subobject:883648|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 17%"|Study
+
!style="width: 20%"|Study
−
!style="width: 15%"|Years of enrollment
+
!style="width: 20%"|Years of enrollment
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 17%"|Comparator
+
!style="width: 20%"|Comparator
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(96)91681-5 Johnson et al. 1996]
+
|[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
−
|1990-1992
+
|1981-1983
 
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
−
|[[#CAP|CAP]]
+
|1. [[Non-small_cell_lung_cancer_-_historical#CAMP|CAMP]]<br>2. [[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide_.28EP.29|EC]]<br> 3. [[#Cisplatin_.26_Vindesine|VC]]
−
|style="background-color:#1a9850"|Superior TTP<sup>1</sup>
+
|style="background-color:#ffffbf"|Seems not superior
−
|
 
 
|-
 
|-
−
|rowspan=2|[https://doi.org/10.1056/NEJM200012143432402 Rai et al. 2000 (CALGB 9011)]
+
|[https://doi.org/10.1200/JCO.1989.7.11.1602 Bonomi et al. 1989 (ECOG E1583)]
−
|rowspan=2|1990-1994
+
|1984-1985
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]
+
|1. [[#Cisplatin_.26_Vinblastine_99|VP]]<br>2. [[#MVP.2FCAMP_99|MVP/CAMP]]<br> 3. [[#Carboplatin_monotherapy_99|Carboplatin]]<br> 4. [[#Iproplatin_monotherapy_77|Iproplatin]]
−
|style="background-color:#1a9850"|Superior PFS
+
|style="background-color:#ffffbf"|Seems not superior
−
|
 
 
|-
 
|-
−
|2. [[#Chlorambucil_.26_Fludarabine_99|Chlorambucil & Fludarabine]]
+
|[https://doi.org/10.1002/1097-0142(19921101)70:9%3C2281::AID-CNCR2820700912%3E3.0.CO;2-9 Veeder et al. 1992]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
+
|NR
−
|
+
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Mitomycin_monotherapy_99|Mitomycin]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 
|-
 
|-
−
|rowspan=2|[http://www.bloodjournal.org/content/98/8/2319.long Leporrier et al. 2001 (FCGCLL 1996)]
+
|[https://doi.org/10.1200/JCO.2001.19.5.1336 Smith et al. 2001]
−
|rowspan=2|1990-1998
+
|1995-1998
−
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
−
|1. [[#CAP|CAP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|2. [[#CHOP|CHOP]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1038/leu.2017.246 Hoechstetter et al. 2017 (GCLLSG CLL1)]
 
−
|1997-2004
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Chronic_lymphocytic_leukemia#Observation|Observation]]
 
−
|style="background-color:#1a9850"|Superior PFS<br>Median PFS: 30.1 vs 12.9 mo
 
−
|
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/3/885.long Eichorst et al. 2005 (GCLLSG CLL4)]
 
−
|1999-2003
 
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#FC|FC]]
+
|[[#MVP_.28Vinblastine.29|MVP]] x 3
−
|style="background-color:#d73027"|Inferior PFS
+
|style="background-color:#ffffbf"|Seems not superior
−
|style="background-color:#ffffbf"|No statistical difference in HRQoL
 
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2006.08.0762 Flinn et al. 2007 (ECOG E2997)]
+
|[https://doi.org/10.1002/cncr.11535 Danson et al. 2003]
−
|1999-NR
+
|1997-2001
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#FC|FC]]
+
|[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29|GC]]
−
|style="background-color:#d73027"|Inferior PFS
+
|style="background-color:#ffffbf"|Seems not superior
−
|
 
−
|-
 
−
|rowspan = "2" |[https://doi.org/10.1016/S0140-6736(07)61125-8 Catovsky et al. 2007 (LRF CLL4)]
 
−
|rowspan=2|1999-2004
 
−
|rowspan = "2" style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|2. [[#FC|FC]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|[http://www.bloodjournal.org/content/114/16/3382.long Eichhorst et al. 2009 (GCLLSG CLL5)]
 
−
|1999-2004
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Chlorambucil_monotherapy|Chlorambucil]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoints of PFS/OS
 
−
|
 
 
|-
 
|-
−
|[https://doi.org/10.1016/S1470-2045(11)70242-X Elter et al. 2011 (CAM 314)]
+
|[https://doi.org/10.1093/annonc/mdl078 Booton et al. 2006 (BTOG1)]
−
|2004-2008
+
|2001-2002
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#Fludarabine_.26_Alemtuzumab|Fludarabine & Alemtuzumab]]
+
|[[Non-small_cell_lung_cancer#Carboplatin_.26_Docetaxel|DCb]]
−
| style="background-color:#fc8d59" |Seems to have inferior OS
+
|style="background-color:#ffffbf"|Seems not superior
−
|
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>The superior endpoint in Johnson et al. 1996 was only observed in this subgroup, not pretreated patients.''<br>
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*CALGB 9011: intended for previously untreated patients with CLL who were high-risk ([[#Original_Rai_staging_.281975.29|Rai stage]] III or IV) or intermediate-risk ([[#Original_Rai_staging_.281975.29|Rai stage]] I or II) if they had at least one of the following: disease-related symptoms such as weight loss, extreme fatigue, night sweats, or fever without evidence of infection; massive or progressive splenomegaly or lymphadenopathy, or more than a 50 percent increase in the number of peripheral-blood lymphocytes over a 2-month period or an anticipated doubling of these cells within less than 12 months.
 
−
*ECOG E2997: intended for untreated patients greater than or equal to 18 years with a diagnosis of progressive CLL using the [[#NCI_Sponsored_Working_Group_Criteria_.281996.29|National Cancer Institute criteria]].''
 
−
*GCLLSG CLL5: intended for untreated patients between 65 and 80 years with [[#Binet_staging_.281981.29|Binet stage]] C, or [[#Binet_staging_.281981.29|Binet stage]] B or A if they had rapid disease progression (lymphocyte doubling time less than 3 months) or symptoms from enlarged lymph nodes and organs, or if they had severe B symptoms.''
 
−
</div>
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Mitomycin (Mutamycin)]]
−
'''28-day cycle for up to 6 to 12 cycles'''
+
*[[Vinblastine (Velban)]]
−
</div></div><br>
+
*[[Cisplatin (Platinol)]]
 +
</div></div>
 +
===References===
 +
# '''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
 +
# '''ECOG E1583:''' Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1989 Nov;7(11):1602-13. [https://doi.org/10.1200/JCO.1989.7.11.1602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2553879 PubMed]
 +
# Veeder MH, Jett JR, Su JQ, Mailliard JA, Foley JF, Dalton RJ, Etzell PS, Marschke RF Jr, Kardinal CG, Maksymiuk AW, Ebbert LP, Tazelaar HD, Witrak GA. A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer. 1992 Nov 1;70(9):2281-7. [https://doi.org/10.1002/1097-0142(19921101)70:9%3C2281::AID-CNCR2820700912%3E3.0.CO;2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1394057 PubMed]
 +
# Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001 Mar 1;19(5):1336-43. [https://doi.org/10.1200/JCO.2001.19.5.1336 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11230476 PubMed]
 +
# Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://doi.org/10.1002/cncr.11535 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12879472 PubMed]
 +
# '''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599 PubMed]
 +
==MVP (Vindesine) {{#subobject:5258ea|Regimen=1}}==
 +
MVP: '''<u>M</u>'''itomycin, '''<u>V</u>'''indesine, '''<u>P</u>'''latinol (Cisplatin)
 +
<br>PVM: '''<u>P</u>'''latinol (Cisplatin), '''<u>V</u>'''indesine, '''<u>M</u>'''itomycin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, PO {{#subobject:d44d0d|Variant=1}}===
+
===Regimen {{#subobject:ffec94|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 810: Line 793:
 
!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/10.1016/S0140-6736(07)61125-8 Catovsky et al. 2007 (LRF CLL4)]
+
|[https://doi.org/10.1093/oxfordjournals.annonc.a058834 González Barón et al. 1994]
−
|rowspan=2|1999-2004
+
|1989-1992
−
|rowspan = "2" style="background-color:#1a9851"|Phase 3 (C)
+
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
−
|1. [[#Chlorambucil_monotherapy|Chlorambucil]]
+
|[[#MIC_3|MIP]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|2. [[#FC|FC]]
+
|[https://doi.org/10.1093/oxfordjournals.annonc.a010761 Gridelli et al. 1996]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+
|1990-1994
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#MEV|MEV]]
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1016/s0169-5002(01)00239-2 Jelić et al. 2001]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|1990-1996
−
====Chemotherapy====
+
|style="background-color:#1a9851"|Phase 3 (C)
−
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
|[[Stub#MVC|MVC]]
−
'''28-day cycle for up to 6 to 12 cycles'''
+
| style="background-color:#d73027" |Inferior OS
−
</div></div>
 
−
===References===
 
−
# Johnson S, Smith AG, Löffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W; French Cooperative Group on CLL. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. Lancet. 1996 May 25;347(9013):1432-8. [https://doi.org/10.1016/S0140-6736(96)91681-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8676625 PubMed]
 
−
# '''CALGB 9011:''' Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000 Dec 14;343(24):1750-7. [https://doi.org/10.1056/NEJM200012143432402 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11114313 PubMed]
 
−
# '''FCGCLL 1996:''' Leporrier M, Chevret S, Cazin B, Boudjerra N, Feugier P, Desablens B, Rapp MJ, Jaubert J, Autrand C, Divine M, Dreyfus B, Maloum K, Travade P, Dighiero G, Binet JL, Chastang C; French Cooperative Group on Chronic Lymphocytic Leukemia. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood. 2001 Oct 15;98(8):2319-25. [http://www.bloodjournal.org/content/98/8/2319.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11588025 PubMed]
 
−
# '''GCLLSG CLL4:''' Eichhorst BF, Busch R, Hopfinger G, Pasold R, Hensel M, Steinbrecher C, Siehl S, Jäger U, Bergmann M, Stilgenbauer S, Schweighofer C, Wendtner CM, Döhner H, Brittinger G, Emmerich B, Hallek M; German CLL Study Group. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006 Feb 1;107(3):885-91. Epub 2005 Oct 11. [http://www.bloodjournal.org/content/107/3/885.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16219797 PubMed] NCT00276848
 
−
## '''HRQoL analysis:''' Eichhorst BF, Busch R, Obwandner T, Kuhn-Hallek I, Herschbach P, Hallek M; German CLL Study Group. Health-related quality of life in younger patients with chronic lymphocytic leukemia treated with fludarabine plus cyclophosphamide or fludarabine alone for first-line therapy: a study by the German CLL Study Group. J Clin Oncol. 2007 May 1;25(13):1722-31. Epub 2007 Mar 26. [https://doi.org/10.1200/JCO.2006.05.6929 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17389338 PubMed]
 
−
<!-- Presented in part at the 46th Annual Meeting of the American Society of Hematology, December 3-7, 2004, San Diego, CA. -->
 
−
# '''ECOG E2997:''' Flinn IW, Neuberg DS, Grever MR, Dewald GW, Bennett JM, Paietta EM, Hussein MA, Appelbaum FR, Larson RA, Moore DF Jr, Tallman MS. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007 Mar 1;25(7):793-8. Epub 2007 Feb 5. [https://doi.org/10.1200/jco.2006.08.0762 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17283364 PubMed] NCT00003764
 
−
## '''Update:''' Lucas DM, Ruppert AS, Lozanski G, Dewald GW, Lozanski A, Claus R, Plass C, Flinn IW, Neuberg DS, Paietta EM, Bennett JM, Jelinek DF, Gribben JG, Hussein MA, Appelbaum FR, Larson RA, Moore DF Jr, Tallman MS, Byrd JC, Grever MR. Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997. Leuk Lymphoma. 2015;56(11):3031-7. Epub 2015 Mar 30. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1023800 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688910/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25721902 PubMed]
 
−
# '''LRF CLL4:''' Catovsky D, Richards S, Matutes E, Oscier D, Dyer MJ, Bezares RF, Pettitt AR, Hamblin T, Milligan DW, Child JA, Hamilton MS, Dearden CE, Smith AG, Bosanquet AG, Davis Z, Brito-Babapulle V, Else M, Wade R, Hillmen P; UK National Cancer Research Institute Haematological Oncology Clinical Studies Group; NCRI Chronic Lymphocytic Leukaemia Working Group. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007 Jul 21;370(9583):230-9. [https://doi.org/10.1016/S0140-6736(07)61125-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17658394 PubMed] NCT00004218
 
−
## '''Update:''' Else M, Wade R, Oscier D, Catovsky D. The long-term outcome of patients in the LRF CLL4 trial: the effect of salvage treatment and biological markers in those surviving 10 years. Br J Haematol. 2016 Jan;172(2):228-37. Epub 2015 Oct 12. [https://doi.org/10.1111/bjh.13824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832371/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26457986 PubMed]
 
−
<!-- Results from an interim analysis were presented, in part, at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003. Preliminary results from the final analysis were presented, in part, at the 14th International CLL Workshop, London, United Kingdom, September 14-16, 2007, as well as at the 49th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 8-11, 2007. -->
 
−
# '''GCLLSG CLL5:''' Eichhorst BF, Busch R, Stilgenbauer S, Stauch M, Bergmann MA, Ritgen M, Kranzhöfer N, Rohrberg R, Söling U, Burkhard O, Westermann A, Goede V, Schweighofer CD, Fischer K, Fink AM, Wendtner CM, Brittinger G, Döhner H, Emmerich B, Hallek M; German CLL Study Group. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009 Oct 15;114(16):3382-91. Epub 2009 Jul 15. [http://www.bloodjournal.org/content/114/16/3382.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19605849 PubMed] NCT00262795
 
−
# '''CAM 314:''' Elter T, Gercheva-Kyuchukova L, Pylylpenko H, Robak T, Jaksic B, Rekhtman G, Kyrcz-Krzemień S, Vatutin M, Wu J, Sirard C, Hallek M, Engert A. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol. 2011 Dec;12(13):1204-13. Epub 2011 Oct 10. [https://doi.org/10.1016/S1470-2045(11)70242-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/21992852 PubMed] NCT00086580
 
−
<!-- # '''Abstract:''' Manuela A. Bergmann, MD, Raymonde Busch, PhD, Barbara Eichhorst, MD, Andreas Buehler, MD, Norbert Fischer, MD, Michael J Eckart, MD, Ursula Vehling-Kaiser, MD, Ulrich Jäger, MD, Georg Hopfinger, MD, Clemens Wendtner, MD, Kirsten Fischer, MD, Bertold Emmerich, MD, Hartmut Döhner, MD, Michael Hallek, M.D. Ph.D. and Stephan Stilgenbauer, MD; German CLL Study Group. Overall Survival In Early Stage Chronic Lymphocytic Leukemia Patients With Treatment Indication Due To Disease Progression: Follow-Up Data Of The CLL1 Trial Of The German CLL Study Group (GCLLSG). Blood 2013 122:4127. [http://www.bloodjournal.org/content/122/21/4127 link to abstract] -->
 
−
#'''GCLLSG CLL1:''' Hoechstetter MA, Busch R, Eichhorst B, Bühler A, Winkler D, Eckart MJ, Vehling-Kaiser U, Schimke H, Jäger U, Hurtz HJ, Hopfinger G, Hartmann F, Fuss H, Abenhardt W, Blau I, Freier W, Müller L, Goebeler M, Wendtner CM, Bahlo J, Fischer K, Bentz M, Emmerich B, Döhner H, Hallek M, Stilgenbauer S. Early, risk-adapted treatment with fludarabine in Binet stage A chronic lymphocytic leukemia patients: results of the CLL1 trial of the German CLL study group. Leukemia. 2017 Dec;31(12):2833-2837. Epub 2017 Aug 14. [https://doi.org/10.1038/leu.2017.246 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28804126/ PubMed] NCT00262782
 
−
==Fludarabine & Prednisone {{#subobject:d4f71b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:408021|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]]
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/82/6/1695.long O'Brien et al. 1993]
+
|[https://doi.org/10.1016/s0959-8049(98)00231-7 Boni et al. 1998]
−
|1988-1991
+
|1992-1996
−
|style="background-color:#91cf61"|Phase 2
+
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#MVP_.28Vindesine.29|MVP]]; CI
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
+
*[[Mitomycin (Mutamycin)]]
−
====Glucocorticoid therapy====
+
*[[Vindesine (Eldisine)]]
−
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Cisplatin (Platinol)]]
−
'''28-day cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M. Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment. Blood. 1993 Sep 15;82(6):1695-700. [http://www.bloodjournal.org/content/82/6/1695.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8400226 PubMed]
+
# González Barón M, Feliu J, Espinosa E, García Girón C, Blanco E, Garrido P, Colmenarejo A, Ordóñez A, Moyano A, de la Gándara I, Zamora P; ONCOPAZ Cooperative Group. Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. Ann Oncol. 1994 Apr;5(4):323-7. [https://doi.org/10.1093/oxfordjournals.annonc.a058834 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8075028 PubMed]
−
## '''Update:''' Keating MJ, O'Brien S, Lerner S, Koller C, Beran M, Robertson LE, Freireich EJ, Estey E, Kantarjian H. Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving fludarabine regimens as initial therapy. Blood. 1998 Aug 15;92(4):1165-71. [http://www.bloodjournal.org/content/92/4/1165.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9694704 PubMed]
+
# Gridelli C, Perrone F, Palmeri S, D'Aprile M, Cognetti F, Rossi A, Gebbia V, Pepe R, Veltri E, Airoma G, Russo A, Incoronato P, Scinto AF, Palazzolo G, Natali M, Leonardi V, Gallo C, De Placido S, Bianco AR; GOSCI. Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. Ann Oncol. 1996 Oct;7(8):821-6. [https://doi.org/10.1093/oxfordjournals.annonc.a010761 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8922196 PubMed]
−
==Fludarabine & Rituximab (FR) {{#subobject:94f00c|Regimen=1}}==
+
# Boni C, Savoldi L, Bisagni G, Ceci G, Crinò L, De Lisi V, Di Costanzo F, Lasagni L, Manenti AL, Moretti G, Rondini E, Sassi M, Zadro A; GOIRC. Bolus versus 5-day continuous infusion of cisplatin with mitomycin and vindesine in the treatment of advanced non-small cell lung cancer (NSCLC): a phase III prospective randomised trial of the Italian Oncology Group for Clinical Research (GOIRC). Eur J Cancer. 1998 Nov;34(12):1974-6. [https://doi.org/10.1016/s0959-8049(98)00231-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10023325 PubMed]
−
FR: '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab
+
# Jelić S, Mitrović L, Radosavljević D, Elezar E, Babović N, Kovcin V, Tomasević Z, Kovacević S, Gavrilović D, Radulović S. Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study. Lung Cancer. 2001 Oct;34(1):1-13. [https://doi.org/10.1016/s0169-5002(01)00239-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11557107 PubMed]
 +
==Paclitaxel monotherapy {{#subobject:a87044|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:4ee0e6|Variant=1}}===
+
===Regimen variant #1, 100 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:866dac|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 875: Line 839:
 
!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/101/1/6.long Byrd et al. 2002 (CALGB 9712)]
+
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ Comella et al. 2004 (SICOG 9909)]
−
|1998-2000
+
|rowspan=2|1999-2003
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
+
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-de-esc)
−
|[[#Fludarabine_monotherapy|F]], then [[Chronic_lymphocytic_leukemia#Rituximab_monotherapy|R]]
+
|1. [[Non-small_cell_lung_cancer#Gemcitabine_monotherapy|Gemcitabine]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of CR rate
+
|style="background-color:#d3d3d3"|Not reported
 +
|-
 +
|2. [[Non-small_cell_lung_cancer#Gemcitabine_.26_Paclitaxel|GT]]<br> 3. [[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|GV]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 20 to 30 minutes once per day on days 1 to 5
+
*[[Paclitaxel (Taxol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
−
====Targeted therapy====
+
'''28-day cycle for up to 6 cycles'''
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1 & 4
 
−
**Cycles 2 to 6: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*Cycle 1: [[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 14
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg IV once per infusion, 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once per infusion, 30 minutes prior to [[Rituximab (Rituxan)]]
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*If restaging done 2 months after 6 cycles of therapy shows SD or better: [[Chronic_lymphocytic_leukemia#Rituximab_monotherapy_2|Rituximab]] consolidation
 
−
</div></div>
 
−
===References===
 
−
<!-- Byrd JC, Peterson B, Park K, Morrison V, Vardiman JW, Jacobson RJ, et al. Rituximab added to fludarabine improves response in previously untreated chronic lymphocytic leukemia: preliminary results from CALGB 9712. Journal of Clinical Oncology 2001;20 (Pt 1):280a. -->
 
−
<!-- Byrd JC, Peterson BL, Park K. Concurrent rituximab and fludarabine has a higher complete response rate than sequential treatment in untreated chronic lymphocytic leukemia (CLL) patients: results from CALGB 9712. Blood 2001;98(1):A-3212. -->
 
−
# '''CALGB 9712:''' Byrd JC, Peterson BL, Morrison VA, Park K, Jacobson R, Hoke E, Vardiman JW, Rai K, Schiffer CA, Larson RA. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003 Jan 1;101(1):6-14. Epub 2002 Jul 5. [http://www.bloodjournal.org/content/101/1/6.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12393429 PubMed]
 
−
## '''Update:''' Byrd JC, Rai K, Peterson BL, Appelbaum FR, Morrison VA, Kolitz JE, Shepherd L, Hines JD, Schiffer CA, Larson RA. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood. 2005 Jan 1;105(1):49-53. Epub 2004 May 11. [http://www.bloodjournal.org/content/105/1/49.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15138165 PubMed]
 
−
## '''Update:''' Woyach JA, Ruppert AS, Heerema NA, Peterson BL, Gribben JG, Morrison VA, Rai KR, Larson RA, Byrd JC. Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712. J Clin Oncol. 2011 Apr 1;29(10):1349-55. Epub 2011 Feb 14. [https://doi.org/10.1200/jco.2010.31.1811 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084002/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21321292 PubMed]
 
−
==Idelalisib & Rituximab {{#subobject:7bacdd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:33cbcc|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/PMC4732760/ O'Brien et al. 2015 (Study 101-08)]
 
−
|2010-NR
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: In a letter dated 3/21/2016, Gilead states that idelalisib should '''not''' be used for first line treatment of CLL.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Idelalisib (Zydelig)]] 150 mg PO twice per day
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 & 2: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''28-day cycle for 12 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients who had not progressed could continue on an extension study
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Susan Mary O'Brien, Nicole Lamanna, Thomas J. Kipps, Ian Flinn, Andrew David Zelenetz, Jan Andreas Burger, Leanne Holes, David Michael Johnson, Jessie Gu, Roger D. Dansey, Ronald L. Dubowy, Steven E. Coutre. A phase II study of the selective phosphatidylinositol 3-kinase delta (PI3Kd) inhibitor idelalisib (GS-1101) in combination with rituximab (R) in treatment-naive patients (pts) ≥65 years with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). J Clin Oncol 31, 2013 (suppl; abstr 7005) [http://meetinglibrary.asco.org/content/117245-132 link to abstract] -->
 
−
# '''Study 101-08:''' O'Brien SM, Lamanna N, Kipps TJ, Flinn I, Zelenetz AD, Burger JA, Keating M, Mitra S, Holes L, Yu AS, Johnson DM, Miller LL, Kim Y, Dansey RD, Dubowy RL, Coutre SE. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chronic lymphocytic leukemia. Blood. 2015 Dec 17;126(25):2686-94. Epub 2015 Oct 15. [http://www.bloodjournal.org/content/126/25/2686.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732760/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26472751 PubMed] NCT01203930
 
−
==Lenalidomide monotherapy {{#subobject:9820ba|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, target 10 mg/day {{#subobject:2c7fe5|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874217/ Chen et al. 2010 (Rev-CLL)]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#9ebcda" |ORR: 56%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] as follows:
 
−
**Cycle 1: 2.5 mg PO once per day on days 1 to 21
 
−
**Cycle 2: Increased if tolerated to 5 mg PO once per day on days 1 to 21
 
−
**Cycle 3 onwards: Increased if tolerated to 10 mg PO once per day on days 1 to 21
 
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 mg PO once per day
 
−
'''28-day cycles'''
 
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, target 15 mg/day {{#subobject:a6761e|Variant=1}}===
+
===Regimen variant #2, 200 mg/m<sup>2</sup> q3wk {{#subobject:5e38ca|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
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 965: Line 863:
 
!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/PMC5420789/ Chanan-Khan et al. 2017 (ORIGIN)]
+
|[https://academic.oup.com/jnci/article/92/13/1074/2909527 Ranson et al. 2000]
−
|2009-2013
+
|1995-1997
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#Chlorambucil_monotherapy|Chlorambucil]]
+
|[[#Best_supportive_care|Best supportive care]]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
 
|}
 
|}
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have been previously published with encouraging non-randomized results.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Lenalidomide (Revlimid)]] 5 mg PO once per day, increased to a target dose of 15 mg PO once per day
+
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
−
'''Continued indefinitely'''
+
'''21-day cycles'''
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, target 25 mg/day {{#subobject:3acdbb|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123422/ Badoux et al. 2011 (MDACC 2006-0715)]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#bfd3e6" |ORR: 65%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 5 mg PO once per day on days 1 to 56, then increased to a target dose of 25 mg PO once per day
 
−
'''Continued indefinitely'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Presented in part at the 49th Annual Meeting of the American Society of Hematology, December 7-11, 2007, Atlanta, GA; at the 50th Annual Meeting of the American Society of Hematology, December 6-9, 2008, San Francisco, CA; and at the International Workshop for CLL October 16-18, 2009, Barcelona, Spain. -->
+
# Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. [https://academic.oup.com/jnci/article/92/13/1074/2909527 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10880550 PubMed]
−
# '''Rev-CLL:''' Chen CI, Bergsagel PL, Paul H, Xu W, Lau A, Dave N, Kukreti V, Wei E, Leung-Hagesteijn C, Li ZH, Brandwein J, Pantoja M, Johnston J, Gibson S, Hernandez T, Spaner D, Trudel S. Single-agent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia. J Clin Oncol. 2011 Mar 20;29(9):1175-81. Epub 2010 Dec 28. [https://doi.org/10.1200/jco.2010.29.8133 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874217/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21189385 PubMed] NCT00751296
+
# '''SICOG 9909:''' Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. [https://doi.org/10.1038/sj.bjc.6602011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15266334 PubMed]
−
## '''Update:''' Chen CI, Paul H, Wang T, Le LW, Dave N, Kukreti V, Nong Wei E, Lau A, Bergsagel PL, Trudel S. Long-term follow-up of a phase 2 trial of single agent lenalidomide in previously untreated patients with chronic lymphocytic leukaemia. Br J Haematol. 2014 Jun;165(5):731-3. Epub 2014 Feb 24. [https://doi.org/10.1111/bjh.12785 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24611934 PubMed]
+
==Vindesine monotherapy {{#subobject:f9f7b9|Regimen=1}}==
−
<!-- Presented in part at the 50th annual meeting of the American Society of Hematology, San Francisco, CA, December 6-8, 2008, and at the American Society of Clinical Oncology Annual Meeting, Chicago, IL, June 4-8, 2010. -->
 
−
# '''MDACC 2006-0715:''' Badoux XC, Keating MJ, Wen S, Lee BN, Sivina M, Reuben J, Wierda WG, O'Brien SM, Faderl S, Kornblau SM, Burger JA, Ferrajoli A. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood. 2011 Sep 29;118(13):3489-98. Epub 2011 Jul 1. [http://www.bloodjournal.org/content/118/13/3489.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123422/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21725050 PubMed]
 
−
## '''Update:''' Strati P, Keating MJ, Wierda WG, Badoux XC, Calin S, Reuben JM, O'Brien S, Kornblau SM, Kantarjian HM, Gao H, Ferrajoli A. Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia. Blood. 2013 Aug 1;122(5):734-7. Epub 2013 Jun 25. [http://www.bloodjournal.org/content/122/5/734.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23801633 PubMed]
 
−
# '''ORIGIN:''' Chanan-Khan A, Egyed M, Robak T, Martinelli de Oliveira FA, Echeveste MA, Dolan S, Desjardins P, Blonski JZ, Mei J, Golany N, Zhang J, Gribben JG. Randomized phase 3 study of lenalidomide versus chlorambucil as first-line therapy for older patients with chronic lymphocytic leukemia (the ORIGIN trial). Leukemia. 2017 May;31(5):1240-1243. Epub 2017 Jan 31. [https://www.nature.com/articles/leu201747 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420789/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28140392 PubMed] NCT00910910
 
−
==R-FCM {{#subobject:290a43|Regimen=1}}==
 
−
R-FCM: '''<u>R</u>'''ituximab, '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone
 
−
<br>FCM-R: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone, '''<u>R</u>'''ituximab
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1 {{#subobject:73c565|Variant=1}}===
+
===Regimen {{#subobject:d123895|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 1,015: Line 888:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1111/j.1365-2141.2010.08317.x Hillmen et al. 2011 (NCRI CLL201)]
+
|[https://doi.org/10.1200/JCO.1986.4.7.1037 Einhorn et al. 1986]
−
|2005-2007
+
|1982-1984
−
|style="background-color:#1a9851"|Randomized Phase 2 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#FCM|FCM]]
+
|1. [[#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br>2. [[#MVP_.28Vindesine.29|MVP]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR at 2 mo
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|}
+
|[https://doi.org/10.1093/oxfordjournals.annonc.a010760 Furuse et al. 1996]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|1991-1993
−
====Targeted therapy====
+
|style="background-color:#1a9851"|Phase 3 (C)
−
*[[Rituximab (Rituxan)]] as follows:
+
|[[#Vinorelbine_monotherapy|Vinorelbine]]
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
+
| style="background-color:#d73027" |Inferior ORR
−
**Cycles 2 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 24 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
*[[Cyclophosphamide (Cytoxan)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
*[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:63498|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2009.22.0442 Bosch et al. 2009]
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycles 2 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] 6 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Pegylated granulocyte colony-stimulating factor]] once on day 4
 
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 5
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose not specified) PO twice per week for up to 9 months after completion of therapy
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with a PR or CR at 3 months: [[#Rituximab_monotherapy_2|Rituximab]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:523a98|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/j.leukres.2009.07.008 Faderl et al. 2009]
 
−
|style="background-color:#91cf61"|Phase 2
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
 
−
**Cycles 2 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] as follows:
+
*[[Vindesine (Eldisine)]]
−
**Cycle 1: 25 mg/m<sup>2</sup>/day (route not specified) on days 2 to 4
 
−
**Cycles 2 to 6: 25 mg/m<sup>2</sup>/day (route not specified) on days 1 to 3
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycle 1: 250 mg/m<sup>2</sup>/day (route not specified) on days 2 to 4
 
−
**Cycles 2 to 6: 250 mg/m<sup>2</sup>/day (route not specified) on days 1 to 3
 
−
*[[Mitoxantrone (Novantrone)]] as follows:
 
−
**Cycle 1: 6 mg/m<sup>2</sup> IV once on day 2
 
−
**Cycles 2 to 6: 6 mg/m<sup>2</sup> IV once on day 2
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 25 to 50 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Ondansetron (Zofran)]] 24 mg IV once, prior to chemotherapy
 
−
*[[Pegfilgrastim (Neulasta)]] (dose not specified) following the last day of each treatment cycle
 
−
*[[:Category:Antivirals|Antiviral]] prophylaxis was at the physician's discretion
 
−
*[[:Category:PCP prophylaxis|PCP]] prophylaxis was at the physician's discretion
 
−
'''4- to 6-week cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Presented in part at the 43rd Annual Meeting of the American Society of Hematology, December 8-11, 2007, Atlanta, GA. -->
+
# Einhorn LH, Loehrer PJ, Williams SD, Meyers S, Gabrys T, Nattan SR, Woodburn R, Drasga R, Songer J, Fisher W, Stephens D, Hui S. Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer. J Clin Oncol. 1986 Jul;4(7):1037-43. [https://doi.org/10.1200/JCO.1986.4.7.1037 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3088219 PubMed]
−
# Bosch F, Abrisqueta P, Villamor N, Terol MJ, González-Barca E, Ferra C, González Diaz M, Abella E, Delgado J, Carbonell F, García Marco JA, Escoda L, Ferrer S, Monzó E, González Y, Estany C, Jarque I, Salamero O, Muntañola A, Montserrat E. Rituximab, fludarabine, cyclophosphamide, and mitoxantrone: a new, highly active chemoimmunotherapy regimen for chronic lymphocytic leukemia. J Clin Oncol. 2009 Sep 20;27(27):4578-84. Epub 2009 Aug 24. [https://doi.org/10.1200/jco.2009.22.0442 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19704063 PubMed] EudraCT 2005-001569-33
+
# Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010760 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8922195 PubMed]
−
## '''Update:''' Abrisqueta P, Villamor N, Terol MJ, González-Barca E, González M, Ferrà C, Abella E, Delgado J, García-Marco JA, González Y, Carbonell F, Ferrer S, Monzó E, Jarque I, Muntañola A, Constants M, Escoda L, Calvo X, Bobillo S, Montoro JB, Montserrat E, Bosch F. Rituximab maintenance after first-line therapy with rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) for chronic lymphocytic leukemia. Blood. 2013 Dec 5;122(24):3951-9. Epub 2013 Oct 11. [http://www.bloodjournal.org/content/122/24/3951.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24124086 PubMed]
+
==Vinorelbine monotherapy {{#subobject:f8gub9|Regimen=1}}==
−
# Faderl S, Wierda W, O'Brien S, Ferrajoli A, Lerner S, Keating MJ. Fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL less than 70 Years. Leuk Res. 2010 Mar;34(3):284-8. Epub 2009 Jul 30. [https://doi.org/10.1016/j.leukres.2009.07.008 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4845644/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19646755 PubMed]
 
−
<!--
 
−
# Hillmen P, Pocock C, Cohen D, Cocks K, Sayala HA, Rawstron A, et al. NCRI CLL201 trial: a randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated CLL. Blood 2007;110(11):752.
 
−
# Hillmen P, Pocock C, Cohen D, Gregory W, Cocks K, Rawstron AC, et al. NCRI CLL201 Trial: a randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated CLL. British Journal of Haematology 2008;141(Suppl 1):119.
 
−
-->
 
−
# '''NCRI CLL201:''' Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, Kennedy DB, Fegan C, Milligan DW, Radford J, Mercieca J, Dearden C, Ezekwisili R, Smith AF, Brown J, Booth GA, Varghese AM, Pocock C; NCRI CLL Sub-Group. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol. 2011 Mar;152(5):570-8. Epub 2011 Jan 14. [https://doi.org/10.1111/j.1365-2141.2010.08317.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21231927 PubMed]
 
−
# '''ADMIRE:''' Munir T, Howard DR, McParland L, Pocock C, Rawstron AC, Hockaday A, Varghese A, Hamblin M, Bloor A, Pettitt A, Fegan C, Blundell J, Gribben JG, Phillips D, Hillmen P. Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL. Leukemia. 2017 Oct;31(10):2085-2093. Epub 2017 Apr 20. [https://doi.org/10.1038/leu.2017.65 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28216660 PubMed] ISRCTN42165735
 
−
==Uracil mustard monotherapy {{#subobject:6440d3|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:969dcc|Variant=1}}===
+
===Regimen {{#subobject:dab895|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.1996.14.10.2774 Crawford et al. 1996]
 +
|1990-1992
 +
|style="background-color:#1a9851"|Randomized (E-RT-switch-ic)
 +
|[[#FULV_88|FULV]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM196104202641603 Kennedy & Theologides 1961]
+
|[https://doi.org/10.1093/oxfordjournals.annonc.a010760 Furuse et al. 1996]
−
| style="background-color:#91cf61" |Non-randomized
+
|1991-1993
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 +
|[[#Vindesine_monotherapy|Vindesine]]
 +
| style="background-color:#1a9850" |Superior ORR
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Uracil mustard]]
+
*[[Vinorelbine (Navelbine)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Kennedy BJ, Theologides A. Uracil mustard, a new alkylating agent for oral administration in the management of patients with leukemia and lymphoma. N Engl J Med. 1961 Apr 20;264:790-3. [https://doi.org/10.1056/NEJM196104202641603 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13752496 PubMed]
+
# Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. [https://doi.org/10.1200/JCO.1996.14.10.2774 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8874339 PubMed]
−
=Subsequent lines of therapy=
+
==VIP {{#subobject:e6f7b9|Regimen=1}}==
−
==CAP {{#subobject:6f74d0|Regimen=1}}==
+
VIP: '''<u>V</u>'''inblastine, '''<u>I</u>'''fosfamide, '''<u>P</u>'''latinol (Cisplatin)
−
CAP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:e29575|Variant=1}}===
+
===Regimen {{#subobject:d00565|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 1,136: Line 948:
 
!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/S0140-6736(96)91681-5 Johnson et al. 1996]
+
|[https://doi.org/10.1093/oxfordjournals.annonc.a010642 Kosmidis et al. 1996a]
−
|1990-1992
+
|1992-1994
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Fludarabine_monotherapy_2|Fludarabine]]
+
|[[#VIP-16_99|VIP-16]]
−
| style="background-color:#fc8d59" |Seems to have inferior ORR<sup>1</sup>
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>The inferior endpoint in Johnson et al. 1996 was only observed in this subgroup, not untreated patients.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Vinblastine (Velban)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Ifosfamide (Ifex)]]
−
====Glucocorticoid therapy====
+
*[[Cisplatin (Platinol)]]
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''1-month cycle for 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Johnson S, Smith AG, Löffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W; French Cooperative Group on CLL. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. Lancet. 1996 May 25;347(9013):1432-8. [https://doi.org/10.1016/S0140-6736(96)91681-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8676625 PubMed]
+
# Kosmidis P, Mylonakis N, Fountzilas G, Pavlidis N, Samantas E, Karabelis A, Kattis K, Skarlos D; HeCOG. A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Ann Oncol. 1996 Jul;7(5):517-20. [https://doi.org/10.1093/oxfordjournals.annonc.a010642 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8839908 PubMed]
−
==Fludarabine monotherapy {{#subobject:005c85|Regimen=1}}==
+
=Maintenance after first-line therapy=
−
F: '''<u>F</u>'''ludarabine
+
==Erlotinib monotherapy {{#subobject:096cdf|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:f9937b|Variant=1}}===
+
===Regimen {{#subobject:16398e|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 1,165: Line 974:
 
!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/74/1/19.long Keating et al. 1989]
+
|[https://doi.org/10.1016/S1470-2045(10)70112-1 Cappuzzo et al. 2010 (SATURN)]
−
|1985-1987
+
|2005-2008
−
| style="background-color:#91cf61" |Non-randomized (RT)
+
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
−
| style="background-color:#d3d3d3" |
+
|[[Non-small_cell_lung_cancer#Placebo_4|Placebo]]
−
| style="background-color:#d3d3d3" |
+
|style="background-color:#1a9850"|Superior PFS
 +
|-
 +
|rowspan=2|[https://doi.org/10.1200/JCO.2011.39.9782 Pérol et al. 2012 (IFCT-GFPC 0502)]
 +
|rowspan=2|2006-2009
 +
|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|1. [[Non-small_cell_lung_cancer#Gemcitabine_monotherapy_2|Gemcitabine]]
 +
|style="background-color:#d3d3d3"|Not reported
 
|-
 
|-
−
|[https://pubmed.ncbi.nlm.nih.gov/1699282 Grever et al. 1990]
+
|2. [[Non-small_cell_lung_cancer#Observation_3|Observation]]
−
|NR in abstract
+
|style="background-color:#1a9850"|Superior PFS
−
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(96)91681-5 Johnson et al. 1996]
+
|[https://doi.org/10.1016/j.lungcan.2016.10.007 Cicènas et al. 2016 (IUNO)]
−
|1990-1992
+
|2011-2014
−
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
+
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
−
|[[#CAP_2|CAP]]
+
|[[Complex_multipart_regimens#IUNO|See link]]
−
| style="background-color:#91cf60" |Seems to have superior ORR<sup>1</sup>
+
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#IUNO|See link]]
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>The superior endpoint in Johnson et al. 1996 was only observed in this subgroup, not untreated patients.''
+
''Note: while SATURN was technically a positive study for erlotinib, the median PFS gain was 1.2 weeks. This study was the basis of an FDA approval in 2010, which was later revised after the results of IUNO became available. The trials included here did not require EGFR mutation as a condition for enrollment.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*SATURN and IUNO: [[Regimen_classes#Platinum_doublet|Platinum-doublet therapy]] x 4
 +
*IFCT-GFPC 0502: [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]] x 4
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Targeted therapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Erlotinib (Tarceva)]] 150 mg PO once per day
−
'''28-day cycle for 6 cycles'''
+
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Keating MJ, Kantarjian H, Talpaz M, Redman J, Koller C, Barlogie B, Velasquez W, Plunkett W, Freireich EJ, McCredie KB. Fludarabine: a new agent with major activity against chronic lymphocytic leukemia. Blood. 1989 Jul;74(1):19-25. [http://www.bloodjournal.org/content/74/1/19.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/2473795 PubMed]
+
# '''SATURN:''' Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Epub 2010 May 20. [https://doi.org/10.1016/S1470-2045(10)70112-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20493771 PubMed] NCT00556712
−
# Grever M, Leiby J, Kraut E, Metz E, Neidhart J, Balcerzak S, Malspeis L. A comprehensive phase I and II clinical investigation of fludarabine phosphate. Semin Oncol. 1990 Oct;17(5 Suppl 8):39-48. [https://pubmed.ncbi.nlm.nih.gov/1699282 PubMed]
+
# '''IFCT-GFPC 0502:''' Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. [https://doi.org/10.1200/JCO.2011.39.9782 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22949150 PubMed] NCT00300586
−
# Johnson S, Smith AG, Löffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W; French Cooperative Group on CLL. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. Lancet. 1996 May 25;347(9013):1432-8. [https://doi.org/10.1016/S0140-6736(96)91681-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8676625 PubMed]
+
# '''IUNO:''' Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [https://doi.org/10.1016/j.lungcan.2016.10.007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27987585 PubMed] NCT01328951
−
==FC {{#subobject:dc4000|Regimen=1}}==
+
=Advanced or metastatic disease, subsequent lines of therapy=
−
FC: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide
+
==Erlotinib monotherapy {{#subobject:c3c726|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:7baff0|Variant=1}}===
+
===Regimen {{#subobject:d27efc|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 1,205: Line 1,022:
 
!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.2006.07.1191 O'Brien et al. 2007 (GENTA GL303)]
+
|[https://doi.org/10.1056/NEJMoa050753 Shepherd et al. 2005 (NCIC-CTG BR.21)]
 
|2001-2003
 
|2001-2003
 +
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer#Placebo_4|Placebo]]
 +
|style="background-color:#1a9850"|Superior OS<br>Median OS: 6.7 vs 4.7 mo<br>(aHR 0.70, 95% CI 0.58-0.85)
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134127/ Herbst et al. 2011 (BeTa)]
 +
|2005-2008
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Erlotinib_.26_Bevacizumab_99|Erlotinib & Bevacizumab]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2010.28.5981 Natale et al. 2011 (ZEST)]
 +
|2006-2007
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Vandetanib_monotherapy_99|Vandetanib]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(11)70385-0 Ciuleanu et al. 2012 (TITAN)]
 +
|2006-2010
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 +
|Investigator's choice of:<br>1a. [[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]<br>1b. [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1002/cncr.28132 Karampeazis et al. 2013 (CT/06.05)]
 +
|2006-2010
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 +
|[[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
 +
|-
 +
|[https://doi.org/10.1200/JCO.2011.39.2993 Scagliotti et al. 2012 (SUN 1087)]
 +
|2007-2009
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#Erlotinib_.26_Sunitinib|Erlotinib & Sunitinib]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70310-3 Garassino et al. 2013 (TAILOR<sub>NSCLC</sub>)]
 +
|2007-2012
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 +
|[[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ Ramalingam et al. 2012 (A7471028)]
 +
|2008-2009
 +
|style="background-color:#1a9851"|Randomized Phase 2 (C)
 +
|[[#Dacomitinib_monotherapy_99|Dacomitinib]]
 +
|style="background-color:#fc8d59"|Seems to have inferior PFS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdu517 Scagliotti et al. 2015 (ADVIGO 1018)]
 +
|2008-2010
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#Erlotinib_.26_Figitumumab|Erlotinib & Figitumumab]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2013.52.4694 Kawaguchi et al. 2014 (DELTA<sub>NSCLC</sub>)]
 +
|2009-2012
 +
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 +
|[[Non-small_cell_lung_cancer#Docetaxel_monotherapy_3|Docetaxel]]
 +
| style="background-color:#fee08b" |Might have inferior PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.2015.63.4154 Urata et al. 2016 (WJOG 5108L)]
 +
|2009-2012
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#OBL-FC_77|OBL-FC]]
+
|[[Non-small_cell_lung_cancer#Gefitinib_monotherapy_2|Gefitinib]]
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
+
|style="background-color:#ffffbf"|Inconclusive whether non-inferior PFS
 +
|-
 +
|[https://doi.org/10.1016/j.lungcan.2016.06.019 Smit et al. 2016 (CurrentS)]
 +
|2010-NR
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Erlotinib_monotherapy_2|Erlotinib]]; high-dose
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/10.1016/j.biopha.2017.02.097 Wang et al. 2017a]
 +
|2010-2014
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Erlotinib.2C_Bevacizumab.2C_Panitumumab_88|Erlotinib, Bevacizumab, Panitumumab]]
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdv288 Yoshioka et al. 2015 (ATTENTION)]
 +
|2011-2012
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#Erlotinib_.26_Tivantinib|Erlotinib & Tivantinib]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2014.60.7317 Scagliotti et al. 2015 (MARQUEE)]
 +
|2011-2012
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Stub#Erlotinib_.26_Tivantinib|Erlotinib & Tivantinib]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(14)70452-8 Ramalingam et al. 2014 (ARCHER 1009)]
 +
|2011-2013
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Dacomitinib_monotherapy_99|Dacomitinib]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/10.1016/j.lungcan.2016.10.007 Cicènas et al. 2016 (IUNO)]
 +
|2011-2014
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Complex_multipart_regimens#IUNO|See link]]
 +
|style="background-color:#ffffbf"|[[Complex_multipart_regimens#IUNO|See link]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 Gridelli et al. 2018 (AvaALL)]
 +
|2011-2015
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|Investigator's choice of:<br>1a. [[#Docetaxel_.26_Bevacizumab_99|Docetaxel & Bevacizumab]]<br>1b. [[#Erlotinib_.26_Bevacizumab_99|Erlotinib & Bevacizumab]]<br>1c. [[#Pemetrexed_.26_Bevacizumab_99|Pemetrexed & Bevacizumab]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2009.26.4556 Robak et al. 2010 (REACH)]
+
|[https://doi.org/10.1200/JCO.2016.69.2160 Spigel et al. 2016 (METLung)]
−
|2003-2007
+
|2012-2013
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#FCR_2|R-FC]]
+
|[[Stub#Erlotinib_.26_Onartuzumab|Erlotinib & Onartuzumab]]
−
|style="background-color:#d73027"|Inferior PFS
+
|style="background-color:#d9ef8b"|Might have superior OS
 
|-
 
|-
−
|[https://doi.org/10.1080/10428194.2016.1233536 Robak et al. 2016 (COMPLEMENT 2)]
+
|[https://doi.org/10.1016/S1470-2045(15)00006-6 Soria et al. 2015 (LUX-Lung 8)]
−
|2008-NR
+
|2012-2014
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[Chronic_lymphocytic_leukemia#O-FC_2|O-FC]]
+
|[[Non-small_cell_lung_cancer#Afatinib_monotherapy|Afatinib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 +
|-
 +
|rowspan=2|[https://doi.org/10.1016/S1470-2045(16)30561-7 Neal et al. 2016 (ECOG-ACRIN 1512)]
 +
|rowspan=2|2013-2014
 +
|rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (C)
 +
|1. [[Non-small_cell_lung_cancer#Cabozantinib_monotherapy|Cabozantinib]]
 
|style="background-color:#d73027"|Inferior PFS
 
|style="background-color:#d73027"|Inferior PFS
 
|-
 
|-
−
|}
+
|2. [[Non-small_cell_lung_cancer#Cabozantinib_.26_Erlotinib|Cabozantinib & Erlotinib]]
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm '''in this context'''.''
+
|style="background-color:#d73027"|Inferior PFS
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*''Note: varied according to reference.''
 
−
*Cycle 1: [[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 7
 
−
*Some patients received:
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per week
 
−
**[[Valacyclovir (Valtrex)]] 500 mg PO once per day
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''GENTA GL303:''' O'Brien S, Moore JO, Boyd TE, Larratt LM, Skotnicki A, Koziner B, Chanan-Khan AA, Seymour JF, Bociek RG, Pavletic S, Rai KR. Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (Bcl-2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2007 Mar 20;25(9):1114-20. Epub 2007 Feb 12. Erratum in: J Clin Oncol. 2008 Feb 10;26(5):820. [https://doi.org/10.1200/JCO.2006.07.1191 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17296974 PubMed] NCT00024440
 
−
## '''Update:''' O'Brien S, Moore JO, Boyd TE, Larratt LM, Skotnicki AB, Koziner B, Chanan-Khan AA, Seymour JF, Gribben J, Itri LM, Rai KR. 5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen. J Clin Oncol. 2009 Nov 1;27(31):5208-12. Epub 2009 Sep 8. [https://doi.org/10.1200/JCO.2009.22.5748 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321078/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19738118 PubMed]
 
−
<!-- Presented in part at the 50th Annual Meeting of the American Society of Hematology, December 6-9, 2008, San Francisco, CA. -->
 
−
# '''REACH:''' Robak T, Dmoszynska A, Solal-Céligny P, Warzocha K, Loscertales J, Catalano J, Afanasiev BV, Larratt L, Geisler CH, Montillo M, Zyuzgin I, Ganly PS, Dartigeas C, Rosta A, Maurer J, Mendila M, Saville MW, Valente N, Wenger MK, Moiseev SI. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010 Apr 1;28(10):1756-65. Epub 2010 Mar 1. [https://doi.org/10.1200/jco.2009.26.4556 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20194844 PubMed] content property of [http://hemonc.org HemOnc.org] NCT00090051
 
−
# '''COMPLEMENT 2:''' Robak T, Warzocha K, Govind Babu K, Kulyaba Y, Kuliczkowski K, Abdulkadyrov K, Loscertales J, Kryachok I, Kłoczko J, Rekhtman G, Homenda W, Błoński JZ, McKeown A, Gorczyca MM, Carey JL, Chang CN, Lisby S, Gupta IV, Grosicki S. Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial. Leuk Lymphoma. 2017 May;58(5):1084-1093. Epub 2016 Oct 12. [https://doi.org/10.1080/10428194.2016.1233536 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27731748 PubMed] NCT00824265
 
−
==HDMP {{#subobject:1c202|Regimen=1}}==
 
−
HDMP: '''<u>H</u>'''igh '''<u>D</u>'''ose, '''<u>M</u>'''ethyl'''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:38a97d|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM196405282702205 Burningham et al. 1964]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7649422/ Goldman et al. 2020 (JUNIPER)]
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
+
|2014-2017
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Abemaciclib_monotherapy_99|Abemaciclib]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 +
''Note: the trials included here did not require EGFR mutation as a condition for enrollment. Given the FDA limitation on use in this setting issued in 2016, these regimens have been moved to the historical page. Note that there is another trial named TAILOR in colorectal cancer and another trial named DELTA in indolent lymphoma.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*JUNIPER: KRAS G12 or G13 mutation
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Glucocorticoid therapy====
+
====Preceding treatment====
−
*[[Methylprednisolone (Solumedrol)]]
+
*IUNO: [[Non-small_cell_lung_cancer#Placebo_4|Placebo]]
−
</div></div>
+
</div>
−
===References===
 
−
# Burningham RA, Restrepo A, Pugh RP, Brown EB, Schlossman SF, Khuri PD, Lessner HE, Harrington WJ. Weekly high-dosage glucocorticosteroid treatment of lymphocytic leukemias and lymphomas. N Engl J Med. 1964 May 28;270:1160-6. [https://doi.org/10.1056/NEJM196405282702205 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14129063 PubMed]
 
−
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:60fc19|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/PMC3387277/ Porter et al. 2011]
 
−
|style="background-color:#ffffbe"|Pilot
 
−
|-
 
−
|}
 
−
''Note: this regimen is of historic interest in this context, this being the first clinical use of CAR-T-cell therapy. It is not FDA approved for this indication.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Targeted therapy====
−
*[[Tisagenlecleucel (Kymriah)]]  
+
*[[Erlotinib (Tarceva)]] 150 mg PO once per day
 +
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011 Aug 25;365(8):725-33. Epub 2011 Aug 10. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. [https://doi.org/10.1056/NEJMoa1103849 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387277/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21830940 PubMed]
+
# '''NCIC-CTG BR.21:''' Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [https://doi.org/10.1056/NEJMoa050753 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16014882 PubMed] NCT00036647
−
## '''Update:''' Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011 Aug 10;3(95):95ra73. [http://stm.sciencemag.org/content/3/95/95ra73.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3393096/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21832238 PubMed]
+
<!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL; 13th Annual World Congress on Lung Cancer, July 31-August 4, 2009, San Francisco, CA; and Joint 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology, September 20-24, 2009, Berlin, Germany. -->
−
## '''Update:''' Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, Ambrose D, Grupp SA, Chew A, Zheng Z, Milone MC, Levine BL, Melenhorst JJ, June CH. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015 Sep 2;7(303):303ra139. [http://stm.sciencemag.org/content/7/303/303ra139.short link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909068/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26333935 PubMed]
+
# '''ZEST:''' Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.28.5981 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21282542 PubMed] NCT00364351
−
[[Category:Chronic lymphocytic leukemia regimens]]
+
## '''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/164 Project Data Sphere]
 +
# '''BeTa:''' Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. [https://doi.org/10.1016/S0140-6736(11)60545-X link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134127/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21621716 PubMed] NCT00130728
 +
# '''TITAN:''' Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. [https://doi.org/10.1016/S1470-2045(11)70385-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22277837 PubMed] NCT00556322
 +
<!-- Presented previously, in part, at the European Society for Medical Oncology Congress, Milan, Italy, October 8-12, 2010; Asia-Pacific Lung Cancer Conference, Seoul, Korea, December 2-4, 2010; and the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010. -->
 +
# '''SUN 1087:''' Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, Wierzbicki RF, Albert I, Thomas M, Miziara JE, Papai ZS, Karaseva N, Thongprasert S, Portulas ED, von Pawel J, Zhang K, Selaru P, Tye L, Chao RC, Govindan R. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2070-8. Epub 2012 May 7. [https://doi.org/10.1200/JCO.2011.39.2993 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22564989 PubMed] NCT00457392
 +
<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL; the 35th Congress of the European Society for Medical Oncology, October 8-12, 2010, Milan, Italy; and the 14th World Conference on Lung Cancer, July 3-7, 2011, Amsterdam, the Netherlands. -->
 +
# '''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22753918 PubMed] NCT00769067
 +
# '''CT/06.05:''' Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. [https://doi.org/10.1002/cncr.28132 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23661337 PubMed] NCT00440414
 +
# '''TAILOR<sub>NSCLC</sub>:''' Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. [https://doi.org/10.1016/S1470-2045(13)70310-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23883922 PubMed] NCT00637910
 +
# '''DELTA<sub>NSCLC</sub>:''' Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. [https://doi.org/10.1200/JCO.2013.52.4694 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24841974 PubMed]
 +
# '''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.[https://doi.org/10.1016/S1470-2045(14)70452-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25439691 PubMed] NCT01360554
 +
# '''ADVIGO 1018:''' Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. [https://doi.org/10.1093/annonc/mdu517 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25395283 PubMed] NCT00673049
 +
# '''LUX-Lung 8:''' Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. [https://doi.org/10.1016/S1470-2045(15)00006-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26156651 PubMed] NCT01523587
 +
##'''Update:''' Goss GD, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Isla D, Morabito A, Min YJ, Ardizzoni A, Bender S, Cseh A, Felip E. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung: Final analysis of the randomised phase 3 LUX-Lung 8 trial. EClinicalMedicine. 2021 Jun 18;37:100940. [https://doi.org/10.1016/j.eclinm.2021.100940 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8225678/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34195574/ PubMed]
 +
# '''ATTENTION:''' Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. Epub 2015 Jul 7. [https://doi.org/10.1093/annonc/mdv288 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26153496 PubMed] NCT01377376
 +
# '''MARQUEE:''' Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. Epub 2015 Jul 13. [https://doi.org/10.1200/JCO.2014.60.7317 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26169611 PubMed] NCT01244191
 +
# '''WJOG 5108L:''' Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.63.4154 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27022112 PubMed] UMIN000002014
 +
# '''CurrentS:''' Smit EF, Wu YL, Gervais R, Zhou C, Felip E, Feng J, Guclu SZ, Hoiczyk M, Dorokhova E, Freudensprung U, Grange S, Perez-Moreno PD, Mitchell L, Reck M. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS). Lung Cancer. 2016 Sep;99:94-101. Epub 2016 Jun 27. [https://doi.org/10.1016/j.lungcan.2016.06.019 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27565921 PubMed] NCT01183858
 +
# '''IUNO:''' Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [https://doi.org/10.1016/j.lungcan.2016.10.007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27987585 PubMed] NCT01328951
 +
# '''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://doi.org/10.1016/S1470-2045(16)30561-7 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638 PubMed] NCT01708954
 +
# '''METLung:''' Spigel DR, Edelman MJ, O'Byrne K, Paz-Ares L, Mocci S, Phan S, Shames DS, Smith D, Yu W, Paton VE, Mok T. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol. 2017 Feb;35(4):412-420. Epub 2016 Dec 12. [https://doi.org/10.1200/JCO.2016.69.2160 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27937096 PubMed] NCT01456325
 +
# Wang Y, Wang H, Jiang Y, Zhang Y, Wang X. A randomized phase III study of combining erlotinib with bevacizumab and panitumumab versus erlotinib alone as second-line therapy for Chinese patients with non-small-cell lung cancer. Biomed Pharmacother. 2017 May;89:875-879. Epub 2017 Mar 6. [https://doi.org/10.1016/j.biopha.2017.02.097 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28282789 PubMed]
 +
# '''AvaALL:''' Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2698039 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30177994 PubMed] NCT01351415
 +
# '''JUNIPER:''' Goldman JW, Mazieres J, Barlesi F, Dragnev KH, Koczywas M, Göskel T, Cortot AB, Girard N, Wesseler C, Bischoff H, Nadal E, Park K, Lu S, Taus A, Cobo M, Estrem ST, Wijayawardana SR, Turner K, Oakley GJ 3rd, Hurt KC, Chiang AY, Hossain AM, John WJ, Paz-Ares L. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER. Front Oncol. 2020 Oct 26;10:578756. [https://doi.org/10.3389/fonc.2020.578756 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7649422/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33194700/ PubMed] NCT02152631
 +
[[Category:Non-small cell lung cancer regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Indolent lymphomas]]
+
[[Category:Lung cancers]]

Revision as of 12:57, 9 February 2023

Back to Top

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main NSCLC page for current regimens.

0 regimens on this page
0 variants on this page


Neoadjuvant therapy

MIC

MIC: Mitomycin, Ifosfamide, Cisplatin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Rosell et al. 1994 1989-1991 Phase 3 (E-esc) No preoperative therapy Superior OS
Depierre et al. 2002 1991-1997 Phase 3 (E-esc) No preoperative therapy Seems not superior

Chemotherapy

Supportive therapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, Mate JL, Li S, Roig J, Olazábal A, Canela M, Ariza A, Skacel Z, Morera-Prat J, Abad A. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994 Jan 20;330(3):153-8. link to original article contains dosing details in manuscript PubMed
  2. Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, Braun D, Breton JL, Lemarié E, Gouva S, Paillot N, Bréchot JM, Janicot H, Lebas FX, Terrioux P, Clavier J, Foucher P, Monchâtre M, Coëtmeur D, Level MC, Leclerc P, Blanchon F, Rodier JM, Thiberville L, Villeneuve A, Westeel V, Chastang C; IFCT. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol. 2002 Jan 1;20(1):247-53. link to original article PubMed

Adjuvant therapy

Radiation therapy

RT: Radiation Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Keller et al. 2000 (ECOG E3590) 1991-1997 Phase 3 (C) EP & RT Did not meet endpoint of OS

Preceding treatment

Radiotherapy

5-week course

References

  1. ECOG E3590: Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH; ECOG. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000 Oct 26;343(17):1217-22. link to original article contains dosing details in abstract PubMed

Induction therapy for locally advanced disease

MIC

MIC: Mitomycin, Ifosfamide, Cisplatin
MIP: Mitomycin, Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sculier et al. 1999 1989-1996 Non-randomized portion of phase 3 RCT
Sculier et al. 2004 1996-2002 Phase 3 (C) SuperMIP Seems not superior

Chemotherapy

Subsequent treatment

  • Sculier et al. 1999: MIP x 3 versus RT
  • Sculier et al. 2004: RT

References

  1. Sculier JP, Paesmans M, Lafitte JJ, Baumöhl J, Thiriaux J, van Cutsem O, Recloux P, Bureau G, Berchier MC, Zacharias C, Mommen P, Bosschaerts T, Berghmans T, van Houtte P, Ninane V, Klastersky J; European Lung Cancer Working Party. A randomised phase III trial comparing consolidation treatment with further chemotherapy to chest irradiation in patients with initially unresectable locoregional non-small-cell lung cancer responding to induction chemotherapy. Ann Oncol. 1999 Mar;10(3):295-303. link to original article PubMed
  2. Sculier JP, Lafitte JJ, Berghmans T, Van Houtte P, Lecomte J, Thiriaux J, Efremidis A, Koumakis G, Giner V, Richez M, Corhay JL, Wackenier P, Lothaire P, Paesmans M, Mommen P, Ninane V; European Lung Cancer Working Party. A phase III randomised study comparing two different dose-intensity regimens as induction chemotherapy followed by thoracic irradiation in patients with advanced locoregional non-small-cell lung cancer. Ann Oncol. 2004 Mar;15(3):399-409. link to original article PubMed

PEV

PEV: Platinol (Cisplatin), Etoposide, Vinblastine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kim et al. 2002 1988-1992 Phase 3 (E-esc) No induction Seems not superior

Chemotherapy

Subsequent treatment

References

  1. Kim TY, Yang SH, Lee SH, Park YS, Im YH, Kang WK, Ha SH, Park CI, Heo DS, Bang YJ, Kim NK. A phase III randomized trial of combined chemoradiotherapy versus radiotherapy alone in locally advanced non-small-cell lung cancer. Am J Clin Oncol. 2002 Jun;25(3):238-43. link to original article PubMed

Definitive therapy for locally advanced disease

MVP & RT

MVP & RT: Mitomycin, Vindesine, Platinol (Cisplatin), Radiation Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Furuse et al. 1999 (JCOG9202) 1992-1994 Phase 3 (E-switch-ic) MVP, then RT Seems to have superior OS

Chemotherapy

Radiotherapy

References

  1. JCOG9202: Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. link to original article PubMed

Consolidation or maintenance after definitive therapy for inoperable disease

Bacillus Calmette-Guérin (BCG) monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pines 1976 1970-1973 Randomized (C) Observation Seems to have superior OS

Preceding treatment

Immunotherapy

References

  1. Pines A. A 5-year controlled study of BCG and radiotherapy inoperable lung cancer. Lancet. 1976 Feb 21;1(7956):380-1. link to original article PubMed

Advanced or metastatic disease, first-line

CAMP

CAMP: Cyclophosphamide, Adriamycin (Doxorubicin), Methotrexate, Procarbazine

Regimen

Study Evidence
Bitran et al. 1978 Non-randomized

Chemotherapy

References

  1. Bitran JD, Desser RK, DeMeester T, Golomb HM. Metastatic non-oat-cell bronchogenic carcinoma: therapy with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP). JAMA. 1978 Dec 15;240(25):2743-6. link to original article PubMed
  2. ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article PubMed

CAP (Platinol)

CAP: Cyclophosphamide, Adriamycin (Doxorubicin), Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Robert et al. 1984 1978-1981 Phase 3 (C) 1. Cyclophosphamide & Doxorubicin (AC)
2. CAMF 		Did not meet endpoint of OS
Miller et al. 1986 (SWOG S8012) 1980-1983 Phase 3 (C) 1. FOMi
2. FOMi/CAP 		Seems to have inferior OS

Chemotherapy

21-day cycles

References

  1. Robert F, Omura GA, Birch R, Krauss S, Oldham R; SECG. Randomized phase III comparison of three doxorubicin-based chemotherapy regimens in advanced non-small cell lung cancer: a Southeastern Cancer Study Group trial. J Clin Oncol. 1984 May;2(5):391-5. link to original article contains dosing details in manuscript PubMed
  2. SWOG S8012: Miller TP, Chen TT, Coltman CA Jr, O'Bryan RM, Vance RB, Weiss GB, Fletcher WS, Stephens RL, Livingston RB. Effect of alternating combination chemotherapy on survival of ambulatory patients with metastatic large-cell and adenocarcinoma of the lung: a Southwest Oncology Group Study. J Clin Oncol. 1986 Apr;4(4):502-8. link to original article PubMed

Carboplatin & Cisplatin

CC: Cisplatin & Carboplatin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sculier et al. 1998 1990-1995 Phase 3 (C) CCI Inferior ORR

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

References

  1. Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. link to original article contains dosing details in abstract PubMed

CCI

CCI: Cisplatin, Carboplatin, Ifosfamide

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sculier et al. 1998 1990-1995 Phase 3 (E-esc) CC Superior ORR
Sculier et al. 2002 1998-2000 Phase 3 (C) 1. CCG
2. IG 		Seems not superior

Chemotherapy

References

  1. Sculier JP, Paesmans M, Thiriaux J, Lecomte J, Bureau G, Giner V, Efremidis A, Lafitte JJ, Berchier MC, Alexopoulos CG, Zacharias C, Mommen P, Ninane V, Klastersky J; European Lung Cancer Working Party. Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. J Clin Oncol. 1998 Apr;16(4):1388-96. link to original article PubMed
  2. Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. link to original article PubMed

Cisplatin monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gandara et al. 1993 1988-1990 Phase 3 (C) 1. HDCP
2. HDCP-M 		Seems not superior
von Pawel et al. 2000 (CATAPULT I) NR Phase 3 (C) Cisplatin & Tirapazamine Inferior OS
Gatzemeier et al. 2000 1995-1996 Phase 3 (C) Cisplatin & Paclitaxel Seems to have inferior TTP

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

References

  1. Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, Neefe JR, Hutchins LF, Roach RW, Grunberg SM, Braun TJ, Natale RB, Balcerzak SP; SWOG. Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol. 1993 May;11(5):873-8. link to original article PubMed
  2. CATAPULT I: von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, Talbot D, Rey A, Butler TW, Hirsh V, Olver I, Bergman B, Ayoub J, Richardson G, Dunlop D, Arcenas A, Vescio R, Viallet J, Treat J. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group: cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J Clin Oncol. 2000 Mar;18(6):1351-9. link to original article contains dosing details in abstract PubMed
  3. Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. link to original article contains dosing details in abstract PubMed

Cisplatin & Pemetrexed

Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Scagliotti et al. 2008 (JMDB) 2004-2005 Phase 3 (E-RT-switch-ic) Cisplatin & Gemcitabine Seems to have non-inferior OS

Note: although this regimen is still current for nonsquamous NSCLC, the JMDB trial was unselected by histology.

Chemotherapy

Supportive therapy

21-day cycle for 4 to 6 cycles

References

  1. JMDB: Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. link to original article contains dosing details in abstract PubMed

Cisplatin & Vinblastine

VP: Vinblastine & Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kosty et al. 1994 (CALGB 8931) 1989-1991 Phase 3 (C) VP & Hydrazine Seems not superior

Chemotherapy

References

  1. CALGB 8931: Kosty MP, Fleishman SB, Herndon JE 2nd, Coughlin K, Kornblith AB, Scalzo A, Morris JC, Mortimer J, Green MR; CALGB. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: a randomized placebo-controlled, double-blind phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1994 Jun;12(6):1113-20. link to original article PubMed

Cisplatin & Vindesine

VP: Vindesine & Platinol (Cisplatin)
VdsC: Vindesine & Cisplatin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ruckdeschel et al. 1986 (ECOG E1581) 1981-1983 Phase 3 (E-de-esc) 1. CAMP
2. EC
3. MVP 		Seems not superior
Rapp et al. 1988 1983-1986 Phase 3 (E-esc) Best supportive care Superior OS
Masutani et al. 1999 1987-1992 Phase 3 (C) 1. PVI
2. PVM 		Seems not superior
Kodani et al. 2002 1987-1992 Phase 3 (C) PVI Seems not superior
Negoro et al. 2003 1995-1998 Phase 3 (C) Cisplatin & Irinotecan Seems not superior
Vansteenkiste et al. 2001 1996-1999 Phase 3 (C) Gemcitabine Seems to have inferior clinical benefit
Kubota et al. 2004 1998-2000 Phase 3 (E-switch-ic) Cisplatin & Docetaxel Seems to have inferior OS

Chemotherapy

References

  1. ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article PubMed
  2. Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. link to original article PubMed
  3. Masutani M, Akusawa H, Kadota A, Ohchi Y, Takahashi N, Tanigawa S, Koya Y, Horie T. A phase III randomized trial of cisplatin plus vindesine versus cisplatin plus vindesine plus mitomycin C versus cisplatin plus vindesine plus ifosfamide for advanced non-small-cell lung cancer. Respirology. 1996 Mar;1(1):49-54. link to original article PubMed
  4. Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. link to original article PubMed
  5. Kodani T, Ueoka H, Kiura K, Tabata M, Takigawa N, Segawa Y, Moritaka T, Hiraki S, Harada M, Tanimoto M. A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors. Lung Cancer. 2002 Jun;36(3):313-9. link to original article PubMed
  6. Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. link to original article link to PMC article contains dosing details in manuscript PubMed
  7. Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. link to original article PubMed

Docetaxel monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Roszkowski et al. 2000 1995-NR Phase 3 (E-esc) Best supportive care Seems to have superior OS
Georgoulias et al. 2007 2002-2004 Phase 3 (C) DG Seems to have inferior OS

Chemotherapy

References

  1. Roszkowski K, Pluzanska A, Krzakowski M, Smith AP, Saigi E, Aasebo U, Parisi A, Pham Tran N, Olivares R, Berille J. A multicenter, randomized, phase III study of docetaxel plus best supportive care versus best supportive care in chemotherapy-naive patients with metastatic or non-resectable localized non-small cell lung cancer (NSCLC). Lung Cancer. 2000 Mar;27(3):145-57. link to original article PubMed
  2. Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. link to original article PubMed

Docetaxel & Gemcitabine

DG: Docetaxel & Gemcitabine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Georgoulias et al. 2007 2002-2004 Phase 3 (E-esc) Docetaxel Seems to have superior OS

Note: while this is a superior arm of a phase III RCT, the comparator (single-agent docetaxel) is not usually used in the first-line treatment and this regimen is not currently recommended by ESMO guidelines.

Chemotherapy

References

  1. Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. link to original article PubMed

Ifosfamide & Gemcitabine

IG: Ifosfamide & Gemcitabine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sculier et al. 2002 1998-2000 Phase 3 (E-esc) 1. CCI
2. CCG 		Seems not superior
Berghmans et al. 2013 (ELCWP-01041) 2003-2009 Phase 3 (C) 1. GIP
2. DP 		Seems not superior

Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.

Chemotherapy

References

  1. Sculier JP, Lafitte JJ, Lecomte J, Berghmans T, Thiriaux J, Florin MC, Efremidis A, Alexopoulos CG, Recloux P, Ninane V, Mommen P, Paesmans M, Klastersky J; European Lung Cancer Working Party. A three-arm phase III randomised trial comparing combinations of platinum derivatives, ifosfamide and/or gemcitabine in stage IV non-small-cell lung cancer. Ann Oncol. 2002 Jun;13(6):874-82. link to original article PubMed
  2. ELCWP-01041: Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. link to original article PubMed NCT00622349

Gemcitabine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Vansteenkiste et al. 2001 1996-1999 Phase 3 (E-de-esc) Cisplatin & Vindesine Seems to have superior clinical benefit
Sederholm et al. 2005 1998-2001 Phase 3 (C) Carboplatin & Gemcitabine Seems to have inferior OS

Note: this regimen is considered current in elderly patients or those with poor PS; these trials were unselected by these parameters.

Chemotherapy

References

  1. Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. link to original article PubMed
  2. Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. link to original article PubMed

GIP

GIP: Gemcitabine, Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence
Sculier et al. 2007 2000-2004 Non-randomized portion of phase 3 RCT

Chemotherapy

References

  1. Sculier JP, Lafitte JJ, Lecomte J, Alexopoulos CG, Van Cutsem O, Giner V, Efremidis A, Berchier MC, Collon T, Meert AP, Scherpereel A, Ninane V, Paesmans M, Berghmans T; European Lung Cancer Working Party. A phase III randomised trial comparing sequential chemotherapy using cisplatin-based regimen and paclitaxel to cisplatin-based chemotherapy alone in advanced non-small-cell lung cancer. Ann Oncol. 2007 Jun;18(6):1037-42. Epub 2007 Apr 2. link to original article PubMed

MACC

MACC: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, CCNU (Lomustine)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Chahinian et al. 1977 NR Non-randomized
Cormier et al. 1982 NR Phase 3 (E-esc) Placebo Superior OS

Chemotherapy

References

  1. Chahinian PA, Arnold DJ, Cohen JM, Purpora DP, Jaffrey IS, Teirstein AS, Kirschner PA, Holland JF. Chemotherapy for bronchogenic carcinoma: methotrexate, doxorubicin, cyclophosphamide, and lomustine. JAMA. 1977 May 30;237(22):2392-6. link to original article PubMed
  2. Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. link to original article PubMed

MIC

MIC: Mitomycin, Ifosfamide, Cisplatin
MIP: Mitomycin, Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cullen et al. 1999 (MIC2) 1988-1996 Phase 3 (E-esc) Best supportive care Seems to have superior OS
Crinò et al. 1999 1995-1997 Phase 3 (C) Cisplatin & Gemcitabine Seems to have inferior ORR
Sculier et al. 2000 1995-1998 Phase 3 (C) CarboMIP Seems not superior
Danson et al. 2003 1997-2001 Phase 3 (C) GC Seems not superior
Booton et al. 2006 (BTOG1) 2001-2002 Phase 3 (C) DCb Seems not superior

Chemotherapy

References

  1. MIC2: Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. link to original article PubMed
  2. Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. link to original article contains dosing details in abstract PubMed
  3. Sculier JP, Lafitte JJ, Paesmans M, Thiriaux J, Alexopoulos CG, Baumöhl J, Schmerber J, Koumakis G, Florin MC, Zacharias C, Berghmans T, Mommen P, Ninane V, Klastersky J. Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer. Br J Cancer. 2000 Nov;83(9):1128-35. link to original article link to PMC article PubMed
  4. Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article PubMed
  5. BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed

MVP (Vinblastine)

MVP: Mitomycin, Vinblastine, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ruckdeschel et al. 1986 (ECOG E1581) 1981-1983 Phase 3 (E-de-esc) 1. CAMP
2. EC
3. VC 		Seems not superior
Bonomi et al. 1989 (ECOG E1583) 1984-1985 Phase 3 (C) 1. VP
2. MVP/CAMP
3. Carboplatin
4. Iproplatin 		Seems not superior
Veeder et al. 1992 NR Phase 3 (C) Mitomycin Might have superior OS
Smith et al. 2001 1995-1998 Phase 3 (C) MVP x 3 Seems not superior
Danson et al. 2003 1997-2001 Phase 3 (C) GC Seems not superior
Booton et al. 2006 (BTOG1) 2001-2002 Phase 3 (C) DCb Seems not superior

Chemotherapy

References

  1. ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article PubMed
  2. ECOG E1583: Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum RH, Green MD, Mason B, Hahn R, Tormey DC, Harris J, Comis R, Glick J. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small-cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol. 1989 Nov;7(11):1602-13. link to original article PubMed
  3. Veeder MH, Jett JR, Su JQ, Mailliard JA, Foley JF, Dalton RJ, Etzell PS, Marschke RF Jr, Kardinal CG, Maksymiuk AW, Ebbert LP, Tazelaar HD, Witrak GA. A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma. Cancer. 1992 Nov 1;70(9):2281-7. link to original article PubMed
  4. Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001 Mar 1;19(5):1336-43. link to original article PubMed
  5. Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article PubMed
  6. BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed

MVP (Vindesine)

MVP: Mitomycin, Vindesine, Platinol (Cisplatin)
PVM: Platinol (Cisplatin), Vindesine, Mitomycin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
González Barón et al. 1994 1989-1992 Phase 3 (E-switch-ic) MIP Seems not superior
Gridelli et al. 1996 1990-1994 Phase 3 (C) MEV Seems not superior
Jelić et al. 2001 1990-1996 Phase 3 (C) MVC Inferior OS
Boni et al. 1998 1992-1996 Phase 3 (C) MVP; CI Seems not superior

Chemotherapy

References

  1. González Barón M, Feliu J, Espinosa E, García Girón C, Blanco E, Garrido P, Colmenarejo A, Ordóñez A, Moyano A, de la Gándara I, Zamora P; ONCOPAZ Cooperative Group. Comparison of two chemotherapeutic regimens--mitomycin + vindesine + cisplatin (MVP) vs mitomycin + ifosfamide + cisplatin (MIP)--in advanced non-small-cell lung cancer. Ann Oncol. 1994 Apr;5(4):323-7. link to original article PubMed
  2. Gridelli C, Perrone F, Palmeri S, D'Aprile M, Cognetti F, Rossi A, Gebbia V, Pepe R, Veltri E, Airoma G, Russo A, Incoronato P, Scinto AF, Palazzolo G, Natali M, Leonardi V, Gallo C, De Placido S, Bianco AR; GOSCI. Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. Ann Oncol. 1996 Oct;7(8):821-6. link to original article PubMed
  3. Boni C, Savoldi L, Bisagni G, Ceci G, Crinò L, De Lisi V, Di Costanzo F, Lasagni L, Manenti AL, Moretti G, Rondini E, Sassi M, Zadro A; GOIRC. Bolus versus 5-day continuous infusion of cisplatin with mitomycin and vindesine in the treatment of advanced non-small cell lung cancer (NSCLC): a phase III prospective randomised trial of the Italian Oncology Group for Clinical Research (GOIRC). Eur J Cancer. 1998 Nov;34(12):1974-6. link to original article PubMed
  4. Jelić S, Mitrović L, Radosavljević D, Elezar E, Babović N, Kovcin V, Tomasević Z, Kovacević S, Gavrilović D, Radulović S. Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study. Lung Cancer. 2001 Oct;34(1):1-13. link to original article PubMed

Paclitaxel monotherapy

Regimen variant #1, 100 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Comella et al. 2004 (SICOG 9909) 1999-2003 Phase 3 (E-de-esc) 1. Gemcitabine Not reported
2. GT
3. GV 		Seems to have inferior OS

Chemotherapy

28-day cycle for up to 6 cycles


Regimen variant #2, 200 mg/m2 q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ranson et al. 2000 1995-1997 Phase 3 (E-esc) Best supportive care Seems to have superior OS

Chemotherapy

21-day cycles

References

  1. Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. link to original article PubMed
  2. SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article contains dosing details in manuscript PubMed

Vindesine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Einhorn et al. 1986 1982-1984 Phase 3 (C) 1. Cisplatin & Vindesine
2. MVP 		Seems not superior
Furuse et al. 1996 1991-1993 Phase 3 (C) Vinorelbine Inferior ORR

Chemotherapy

References

  1. Einhorn LH, Loehrer PJ, Williams SD, Meyers S, Gabrys T, Nattan SR, Woodburn R, Drasga R, Songer J, Fisher W, Stephens D, Hui S. Random prospective study of vindesine versus vindesine plus high-dose cisplatin versus vindesine plus cisplatin plus mitomycin C in advanced non-small-cell lung cancer. J Clin Oncol. 1986 Jul;4(7):1037-43. link to original article PubMed
  2. Furuse K, Fukuoka M, Kuba M, Yamori S, Nakai Y, Negoro S, Katagami N, Takada Y, Kinuwaki E, Kawahara M, Kubota K, Sakuma A, Niitani H; Japan Vinorelbine Lung Cancer Cooperative Study Group. Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). Ann Oncol. 1996 Oct;7(8):815-20. link to original article PubMed

Vinorelbine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Crawford et al. 1996 1990-1992 Randomized (E-RT-switch-ic) FULV Seems to have superior OS
Furuse et al. 1996 1991-1993 Phase 3 (E-switch-ic) Vindesine Superior ORR

Chemotherapy

References

  1. Crawford J, O'Rourke M, Schiller JH, Spiridonidis CH, Yanovich S, Ozer H, Langleben A, Hutchins L, Koletsky A, Clamon G, Burman S, White R, Hohneker J. Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer. J Clin Oncol. 1996 Oct;14(10):2774-84. Erratum in: J Clin Oncol 1996 Dec;14(12):3175. Spiridonitis CH [corrected to Spiridonidis CH]. link to original article PubMed

VIP

VIP: Vinblastine, Ifosfamide, Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kosmidis et al. 1996a 1992-1994 Phase 3 (C) VIP-16 Seems not superior

Chemotherapy

References

  1. Kosmidis P, Mylonakis N, Fountzilas G, Pavlidis N, Samantas E, Karabelis A, Kattis K, Skarlos D; HeCOG. A prospective randomized phase III study in non-small-cell lung cancer comparing cisplatin, ifosfamide, vinblastine (VIP) versus cisplatin, ifosfamide and etoposide (VIP-16). Ann Oncol. 1996 Jul;7(5):517-20. link to original article PubMed

Maintenance after first-line therapy

Erlotinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cappuzzo et al. 2010 (SATURN) 2005-2008 Phase 3 (E-RT-esc) Placebo Superior PFS
Pérol et al. 2012 (IFCT-GFPC 0502) 2006-2009 Phase 3 (E-esc) 1. Gemcitabine Not reported
2. Observation Superior PFS
Cicènas et al. 2016 (IUNO) 2011-2014 Phase 3 (E-RT-switch-ic) See link See link

Note: while SATURN was technically a positive study for erlotinib, the median PFS gain was 1.2 weeks. This study was the basis of an FDA approval in 2010, which was later revised after the results of IUNO became available. The trials included here did not require EGFR mutation as a condition for enrollment.

Preceding treatment

Targeted therapy

Continued indefinitely

References

  1. SATURN: Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Epub 2010 May 20. link to original article contains dosing details in abstract PubMed NCT00556712
  2. IFCT-GFPC 0502: Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original article contains dosing details in manuscript PubMed NCT00300586
  3. IUNO: Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article contains dosing details in manuscript PubMed NCT01328951

Advanced or metastatic disease, subsequent lines of therapy

Erlotinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Shepherd et al. 2005 (NCIC-CTG BR.21) 2001-2003 Phase 3 (E-RT-esc) Placebo Superior OS
Median OS: 6.7 vs 4.7 mo
(aHR 0.70, 95% CI 0.58-0.85)
Herbst et al. 2011 (BeTa) 2005-2008 Phase 3 (C) Erlotinib & Bevacizumab Did not meet primary endpoint of OS
Natale et al. 2011 (ZEST) 2006-2007 Phase 3 (C) Vandetanib Did not meet primary endpoint of PFS
Ciuleanu et al. 2012 (TITAN) 2006-2010 Phase 3 (E-switch-ooc) Investigator's choice of:
1a. Docetaxel
1b. Pemetrexed 		Did not meet primary endpoint of OS
Karampeazis et al. 2013 (CT/06.05) 2006-2010 Phase 3 (E-switch-ooc) Pemetrexed Did not meet primary endpoint of TTP
Scagliotti et al. 2012 (SUN 1087) 2007-2009 Phase 3 (C) Erlotinib & Sunitinib Did not meet primary endpoint of OS
Garassino et al. 2013 (TAILORNSCLC) 2007-2012 Phase 3 (E-switch-ooc) Docetaxel Seems to have inferior OS
Ramalingam et al. 2012 (A7471028) 2008-2009 Randomized Phase 2 (C) Dacomitinib Seems to have inferior PFS
Scagliotti et al. 2015 (ADVIGO 1018) 2008-2010 Phase 3 (C) Erlotinib & Figitumumab Did not meet primary endpoint of OS
Kawaguchi et al. 2014 (DELTANSCLC) 2009-2012 Phase 3 (E-switch-ooc) Docetaxel Might have inferior PFS
Urata et al. 2016 (WJOG 5108L) 2009-2012 Phase 3 (C) Gefitinib Inconclusive whether non-inferior PFS
Smit et al. 2016 (CurrentS) 2010-NR Phase 3 (C) Erlotinib; high-dose Did not meet primary endpoint of PFS
Wang et al. 2017a 2010-2014 Phase 3 (C) Erlotinib, Bevacizumab, Panitumumab Seems to have inferior OS
Yoshioka et al. 2015 (ATTENTION) 2011-2012 Phase 3 (C) Erlotinib & Tivantinib Did not meet primary endpoint of OS
Scagliotti et al. 2015 (MARQUEE) 2011-2012 Phase 3 (C) Erlotinib & Tivantinib Did not meet primary endpoint of OS
Ramalingam et al. 2014 (ARCHER 1009) 2011-2013 Phase 3 (C) Dacomitinib Did not meet primary endpoint of PFS
Cicènas et al. 2016 (IUNO) 2011-2014 Phase 3 (C) See link See link
Gridelli et al. 2018 (AvaALL) 2011-2015 Phase 3 (C) Investigator's choice of:
1a. Docetaxel & Bevacizumab
1b. Erlotinib & Bevacizumab
1c. Pemetrexed & Bevacizumab 		Did not meet primary endpoint of OS
Spigel et al. 2016 (METLung) 2012-2013 Phase 3 (C) Erlotinib & Onartuzumab Might have superior OS
Soria et al. 2015 (LUX-Lung 8) 2012-2014 Phase 3 (C) Afatinib Seems to have inferior OS1
Neal et al. 2016 (ECOG-ACRIN 1512) 2013-2014 Randomized Phase 2 (C) 1. Cabozantinib Inferior PFS
2. Cabozantinib & Erlotinib Inferior PFS
Goldman et al. 2020 (JUNIPER) 2014-2017 Phase 3 (C) Abemaciclib Did not meet primary endpoint of OS

1Reported efficacy is based on the 2021 update.
Note: the trials included here did not require EGFR mutation as a condition for enrollment. Given the FDA limitation on use in this setting issued in 2016, these regimens have been moved to the historical page. Note that there is another trial named TAILOR in colorectal cancer and another trial named DELTA in indolent lymphoma.

Biomarker eligibility criteria

  • JUNIPER: KRAS G12 or G13 mutation

Preceding treatment

Targeted therapy

Continued indefinitely

References

  1. NCIC-CTG BR.21: Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. link to original article contains dosing details in abstract PubMed NCT00036647
  2. ZEST: Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. Epub 2011 Jan 31. link to original article contains dosing details in abstract PubMed NCT00364351
    1. Dataset: Project Data Sphere
  3. BeTa: Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. link to original article link to PMC article contains dosing details in abstract PubMed NCT00130728
  4. TITAN: Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. link to original article contains dosing details in abstract PubMed NCT00556322
  5. SUN 1087: Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, Wierzbicki RF, Albert I, Thomas M, Miziara JE, Papai ZS, Karaseva N, Thongprasert S, Portulas ED, von Pawel J, Zhang K, Selaru P, Tye L, Chao RC, Govindan R. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2070-8. Epub 2012 May 7. link to original article contains dosing details in abstract PubMed NCT00457392
  6. A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. link to original article link to PMC article PubMed NCT00769067
  7. CT/06.05: Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. link to original article contains dosing details in manuscript PubMed NCT00440414
  8. TAILORNSCLC: Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. link to original article contains dosing details in manuscript PubMed NCT00637910
  9. DELTANSCLC: Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. link to original article contains dosing details in manuscript PubMed
  10. ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.link to original article PubMed NCT01360554
  11. ADVIGO 1018: Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. link to original article PubMed NCT00673049
  12. LUX-Lung 8: Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. link to original article contains dosing details in abstract PubMed NCT01523587
    1. Update: Goss GD, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Isla D, Morabito A, Min YJ, Ardizzoni A, Bender S, Cseh A, Felip E. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung: Final analysis of the randomised phase 3 LUX-Lung 8 trial. EClinicalMedicine. 2021 Jun 18;37:100940. link to original article link to PMC article PubMed
  13. ATTENTION: Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. Epub 2015 Jul 7. link to original article PubMed NCT01377376
  14. MARQUEE: Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. Epub 2015 Jul 13. link to original article contains dosing details in abstract PubMed NCT01244191
  15. WJOG 5108L: Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. link to original article contains dosing details in manuscript PubMed UMIN000002014
  16. CurrentS: Smit EF, Wu YL, Gervais R, Zhou C, Felip E, Feng J, Guclu SZ, Hoiczyk M, Dorokhova E, Freudensprung U, Grange S, Perez-Moreno PD, Mitchell L, Reck M. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS). Lung Cancer. 2016 Sep;99:94-101. Epub 2016 Jun 27. link to original article PubMed NCT01183858
  17. IUNO: Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article contains dosing details in manuscript PubMed NCT01328951
  18. ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article contains dosing details in abstract link to PMC article PubMed NCT01708954
  19. METLung: Spigel DR, Edelman MJ, O'Byrne K, Paz-Ares L, Mocci S, Phan S, Shames DS, Smith D, Yu W, Paton VE, Mok T. Results from the phase III randomized trial of onartuzumab plus erlotinib versus erlotinib in previously treated stage IIIB or IV non-small-cell lung cancer: METLung. J Clin Oncol. 2017 Feb;35(4):412-420. Epub 2016 Dec 12. link to original article contains dosing details in manuscript PubMed NCT01456325
  20. Wang Y, Wang H, Jiang Y, Zhang Y, Wang X. A randomized phase III study of combining erlotinib with bevacizumab and panitumumab versus erlotinib alone as second-line therapy for Chinese patients with non-small-cell lung cancer. Biomed Pharmacother. 2017 May;89:875-879. Epub 2017 Mar 6. link to original article PubMed
  21. AvaALL: Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. link to original article link to PMC article contains dosing details in supplement PubMed NCT01351415
  22. JUNIPER: Goldman JW, Mazieres J, Barlesi F, Dragnev KH, Koczywas M, Göskel T, Cortot AB, Girard N, Wesseler C, Bischoff H, Nadal E, Park K, Lu S, Taus A, Cobo M, Estrem ST, Wijayawardana SR, Turner K, Oakley GJ 3rd, Hurt KC, Chiang AY, Hossain AM, John WJ, Paz-Ares L. A Randomized Phase III Study of Abemaciclib Versus Erlotinib in Patients with Stage IV Non-small Cell Lung Cancer With a Detectable KRAS Mutation Who Failed Prior Platinum-Based Therapy: JUNIPER. Front Oncol. 2020 Oct 26;10:578756. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02152631
Retrieved from "https://hemonc.org/w/index.php?title=Staging_page&oldid=66087"