Difference between revisions of "Esophageal cancer"
m (Text replacement - "style="background-color:#1a9851" |Phase III" to "style="background-color:#1a9851" |Phase 3") |
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|[https://doi.org/10.1093/annonc/mdy105 Ruhstaller et al. 2018 (SAKK 75/08)] | |[https://doi.org/10.1093/annonc/mdy105 Ruhstaller et al. 2018 (SAKK 75/08)] | ||
|2010-2013 | |2010-2013 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|Cisplatin, Docetaxel, Cetuximab | |Cisplatin, Docetaxel, Cetuximab | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 137: | Line 137: | ||
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)08651-8/fulltext Girling et al. 2002 (UK MRC OE02)] | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)08651-8/fulltext Girling et al. 2002 (UK MRC OE02)] | ||
|1992-1998 | |1992-1998 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> | ||
Line 164: | Line 164: | ||
|[https://link.springer.com/article/10.1245%2Fs10434-011-2049-9 Ando et al. 2011 (JCOG 9907)] | |[https://link.springer.com/article/10.1245%2Fs10434-011-2049-9 Ando et al. 2011 (JCOG 9907)] | ||
|2000-2006 | |2000-2006 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|Adjuvant CF]] | |[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|Adjuvant CF]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 189: | Line 189: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJM199812313392704 Kelsen et al. 1998 (RTOG 8911)] | |[https://www.nejm.org/doi/full/10.1056/NEJM199812313392704 Kelsen et al. 1998 (RTOG 8911)] | ||
|1990-1995 | |1990-1995 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
Line 195: | Line 195: | ||
|[https://onlinelibrary.wiley.com/doi/full/10.1002/1097-0142%2820010601%2991%3A11%3C2165%3A%3AAID-CNCR1245%3E3.0.CO%3B2-H Ancona et al. 2001] | |[https://onlinelibrary.wiley.com/doi/full/10.1002/1097-0142%2820010601%2991%3A11%3C2165%3A%3AAID-CNCR1245%3E3.0.CO%3B2-H Ancona et al. 2001] | ||
|1992-1997 | |1992-1997 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
Line 636: | Line 636: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1112088 van Hagen et al. 2012 (CROSS)] | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1112088 van Hagen et al. 2012 (CROSS)] | ||
|2004-2008 | |2004-2008 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>10-year OS: 38% vs 25%<br>(HR 0.70, 95% CI 0.55-0.89) | | style="background-color:#1a9850" |Superior OS<sup>1</sup><br>10-year OS: 38% vs 25%<br>(HR 0.70, 95% CI 0.55-0.89) | ||
Line 728: | Line 728: | ||
|[https://doi.org/10.1200/JCO.2013.53.6532 Mariette et al. 2014 (FFCD 9901)] | |[https://doi.org/10.1200/JCO.2013.53.6532 Mariette et al. 2014 (FFCD 9901)] | ||
|2000-2009 | |2000-2009 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
Line 791: | Line 791: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70288-6/fulltext Burmeister et al. 2005] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70288-6/fulltext Burmeister et al. 2005] | ||
|1994-2000 | |1994-2000 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
Line 821: | Line 821: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126644/ Tepper et al. 2008 (CALGB 9781)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126644/ Tepper et al. 2008 (CALGB 9781)] | ||
|1997-2000 | |1997-2000 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
Line 949: | Line 949: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145832/ Yang et al. 2018 (NEOCRTEC5010)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145832/ Yang et al. 2018 (NEOCRTEC5010)] | ||
|2007-2014 | |2007-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant therapy]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant therapy]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 979: | Line 979: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145832/ Yang et al. 2018 (NEOCRTEC5010)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145832/ Yang et al. 2018 (NEOCRTEC5010)] | ||
|2007-2014 | |2007-2014 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant therapy]] | |[[Esophageal_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant therapy]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 1,139: | Line 1,139: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract Crosby et al. 2013 (SCOPE-1)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract Crosby et al. 2013 (SCOPE-1)] | ||
|2008-2012 | |2008-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[Stub#Capecitabine.2C_Cisplatin.2C_Cetuximab.2C_RT|Capecitabine, Cisplatin, Cetuximab, RT]] | |[[Stub#Capecitabine.2C_Cisplatin.2C_Cetuximab.2C_RT|Capecitabine, Cisplatin, Cetuximab, RT]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup> | ||
Line 1,249: | Line 1,249: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract Crosby et al. 2013 (SCOPE-1)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract Crosby et al. 2013 (SCOPE-1)] | ||
|2008-2012 | |2008-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[Stub#Capecitabine.2C_Cisplatin.2C_Cetuximab.2C_RT|Capecitabine, Cisplatin, Cetuximab, RT]] | |[[Stub#Capecitabine.2C_Cisplatin.2C_Cetuximab.2C_RT|Capecitabine, Cisplatin, Cetuximab, RT]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup> | ||
Line 1,279: | Line 1,279: | ||
|[https://doi.org/10.1200/jco.2002.20.5.1167 Minsky et al. 2002 (RTOG 94-05)] | |[https://doi.org/10.1200/jco.2002.20.5.1167 Minsky et al. 2002 (RTOG 94-05)] | ||
|1995-1999 | |1995-1999 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|Cisplatin, 5-FU, high-dose RT | |Cisplatin, 5-FU, high-dose RT | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS24 | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS24 | ||
Line 1,285: | Line 1,285: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | ||
|2004-2011 | |2004-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | | style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
Line 1,320: | Line 1,320: | ||
|[https://doi.org/10.1200/jco.2005.04.7118 Bedenne et al. 2007 (FFCD 9102)] | |[https://doi.org/10.1200/jco.2005.04.7118 Bedenne et al. 2007 (FFCD 9102)] | ||
|1993-2000 | |1993-2000 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) |
|[[Surgery#Esophageal_cancer_surgery|Surgery]] | |[[Surgery#Esophageal_cancer_surgery|Surgery]] | ||
| style="background-color:#eeee01" |Equivalent OS | | style="background-color:#eeee01" |Equivalent OS | ||
Line 1,356: | Line 1,356: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)] | |[https://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)] | ||
|1986-1990 | |1986-1990 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Radiation_therapy|Radiation therapy]] | |[[#Radiation_therapy|Radiation therapy]] | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
Line 1,403: | Line 1,403: | ||
|[https://jamanetwork.com/journals/jamaoncology/fullarticle/2643119 Suntharalingam et al. 2017 (RTOG 0436)] | |[https://jamanetwork.com/journals/jamaoncology/fullarticle/2643119 Suntharalingam et al. 2017 (RTOG 0436)] | ||
|2008-2013 | |2008-2013 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|Cisplatin, Paclitaxel, Cetuximab, RT | |Cisplatin, Paclitaxel, Cetuximab, RT | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
Line 1,441: | Line 1,441: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | ||
|2004-2011 | |2004-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | | style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
Line 1,485: | Line 1,485: | ||
|[https://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)] | |[https://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)] | ||
|1986-1990 | |1986-1990 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT_2|Cisplatin, 5-FU, RT]] | |[[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT_2|Cisplatin, 5-FU, RT]] | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
Line 1,527: | Line 1,527: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | ||
|2004-2011 | |2004-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | | style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
Line 1,567: | Line 1,567: | ||
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract Conroy et al. 2014 (PRODIGE5/ACCORD17)] | ||
|2004-2011 | |2004-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | | style="background-color:#ffffbf" |[[Complex_multipart_regimens#PRODIGE5.2FACCORD17|See link]] | ||
Line 1,631: | Line 1,631: | ||
|[https://doi.org/10.1200/JCO.2003.12.095 Ando et al. 2003 (JCOG 9204)] | |[https://doi.org/10.1200/JCO.2003.12.095 Ando et al. 2003 (JCOG 9204)] | ||
|1992-1997 | |1992-1997 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Esophageal_cancer_-_null_regimens#Observation|Observation]] | |[[Esophageal_cancer_-_null_regimens#Observation|Observation]] | ||
| style="background-color:#91cf60" |Seems to have superior DFS | | style="background-color:#91cf60" |Seems to have superior DFS | ||
Line 1,637: | Line 1,637: | ||
|[https://link.springer.com/article/10.1245%2Fs10434-011-2049-9 Ando et al. 2011 (JCOG 9907)] | |[https://link.springer.com/article/10.1245%2Fs10434-011-2049-9 Ando et al. 2011 (JCOG 9907)] | ||
|2000-2006 | |2000-2006 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Cisplatin_.26_Fluorouracil_.28CF.29|Neoadjuvant CF]] | |[[#Cisplatin_.26_Fluorouracil_.28CF.29|Neoadjuvant CF]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
Line 1,674: | Line 1,674: | ||
|[https://doi.org/10.1056/nejmoa2032125 Kelly et al. 2021 (CheckMate 577)] | |[https://doi.org/10.1056/nejmoa2032125 Kelly et al. 2021 (CheckMate 577)] | ||
|2016-2019 | |2016-2019 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
|[[Esophageal_cancer_-_null_regimens#Placebo|Placebo]] | |[[Esophageal_cancer_-_null_regimens#Placebo|Placebo]] | ||
| style="background-color:#1a9850" |Superior DFS | | style="background-color:#1a9850" |Superior DFS | ||
Line 1,741: | Line 1,741: | ||
|[https://doi.org/10.1016/s0140-6736(21)01234-4 Sun et al. 2021 (KEYNOTE-590)] | |[https://doi.org/10.1016/s0140-6736(21)01234-4 Sun et al. 2021 (KEYNOTE-590)] | ||
|2017-2019 | |2017-2019 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]] | |[[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]] | ||
| style="background-color:#1a9850" |Superior OS<br>Median OS: 12.4 vs 9.8 mo<br>(HR 0.73, 95% CI 0.62-0.86) | | style="background-color:#1a9850" |Superior OS<br>Median OS: 12.4 vs 9.8 mo<br>(HR 0.73, 95% CI 0.62-0.86) | ||
Line 1,931: | Line 1,931: | ||
|[https://doi.org/10.1200/jco.2002.08.105 Ross et al. 2002] | |[https://doi.org/10.1200/jco.2002.08.105 Ross et al. 2002] | ||
|1995-1998 | |1995-1998 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#MCF|MCF]] | |[[#MCF|MCF]] | ||
| style="background-color:#eeee01" |Seems to have non-inferior OS | | style="background-color:#eeee01" |Seems to have non-inferior OS | ||
Line 1,937: | Line 1,937: | ||
| rowspan="3" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | | rowspan="3" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | ||
|rowspan=3|2000-2005 | |rowspan=3|2000-2005 | ||
− | | rowspan="3" style="background-color:#1a9851" |Phase | + | | rowspan="3" style="background-color:#1a9851" |Phase 3 (C) |
|1. [[#ECX_2|ECX]] | |1. [[#ECX_2|ECX]] | ||
| style="background-color:#eeee01" |Non-inferior OS | | style="background-color:#eeee01" |Non-inferior OS | ||
Line 1,990: | Line 1,990: | ||
| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | | rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | ||
|rowspan=2|2000-2005 | |rowspan=2|2000-2005 | ||
− | | rowspan="2" style="background-color:#1a9851" |Phase | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|1. [[#ECF_2|ECF]] | |1. [[#ECF_2|ECF]] | ||
| style="background-color:#eeee01" |Non-inferior OS | | style="background-color:#eeee01" |Non-inferior OS | ||
Line 2,028: | Line 2,028: | ||
| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | | rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | ||
|rowspan=2|2000-2005 | |rowspan=2|2000-2005 | ||
− | | rowspan="2" style="background-color:#1a9851" |Phase | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|1. [[#ECF_2|ECF]]<br> 2. [[#ECX_2|ECX]] | |1. [[#ECF_2|ECF]]<br> 2. [[#ECX_2|ECX]] | ||
| style="background-color:#eeee01" |Non-inferior OS | | style="background-color:#eeee01" |Non-inferior OS | ||
Line 2,071: | Line 2,071: | ||
| rowspan="3" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | | rowspan="3" |[https://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)] | ||
|rowspan=3|2000-2005 | |rowspan=3|2000-2005 | ||
− | | rowspan="3" style="background-color:#1a9851" |Phase | + | | rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|1. [[#ECF_2|ECF]] | |1. [[#ECF_2|ECF]] | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 2,083: | Line 2,083: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ Waddell et al. 2013 (REAL3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ Waddell et al. 2013 (REAL3)] | ||
|2008-2011 | |2008-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|mEOC+P | |mEOC+P | ||
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
Line 2,229: | Line 2,229: | ||
|[https://doi.org/10.1200/jco.2002.08.105 Ross et al. 2002] | |[https://doi.org/10.1200/jco.2002.08.105 Ross et al. 2002] | ||
|1995-1998 | |1995-1998 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[#ECF_2|ECF]] | |[[#ECF_2|ECF]] | ||
| style="background-color:#eeee01" |Seems to have non-inferior OS | | style="background-color:#eeee01" |Seems to have non-inferior OS | ||
Line 2,371: | Line 2,371: | ||
|[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | |[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | ||
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Pembrolizumab_monotherapy|Pembrolizumab]] | |[[#Pembrolizumab_monotherapy|Pembrolizumab]] | ||
| style="background-color:#d73027" |Inferior OS<sup>1</sup> | | style="background-color:#d73027" |Inferior OS<sup>1</sup> | ||
Line 2,484: | Line 2,484: | ||
|[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | |[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | ||
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Pembrolizumab_monotherapy|Pembrolizumab]] | |[[#Pembrolizumab_monotherapy|Pembrolizumab]] | ||
| style="background-color:#d73027" |Inferior OS<sup>1</sup> | | style="background-color:#d73027" |Inferior OS<sup>1</sup> | ||
Line 2,564: | Line 2,564: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444575/ Huang et al. 2019 (ESWN 01)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444575/ Huang et al. 2019 (ESWN 01)] | ||
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[#S-1_monotherapy|S-1]] | |[[#S-1_monotherapy|S-1]] | ||
| style="background-color:#1a9850" |Superior PFS | | style="background-color:#1a9850" |Superior PFS | ||
Line 2,621: | Line 2,621: | ||
|[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | |[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | ||
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Pembrolizumab_monotherapy|Pembrolizumab]] | |[[#Pembrolizumab_monotherapy|Pembrolizumab]] | ||
| style="background-color:#d73027" |Inferior OS<sup>1</sup> | | style="background-color:#d73027" |Inferior OS<sup>1</sup> | ||
Line 2,644: | Line 2,644: | ||
|[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | |[https://doi.org/10.1200/jco.20.01888 Kojima et al. 2020 (KEYNOTE-181)] | ||
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Pembrolizumab_monotherapy|Pembrolizumab]] | |[[#Pembrolizumab_monotherapy|Pembrolizumab]] | ||
| style="background-color:#d73027" |Inferior OS<sup>1</sup> | | style="background-color:#d73027" |Inferior OS<sup>1</sup> | ||
Line 2,677: | Line 2,677: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444575/ Huang et al. 2019 (ESWN 01)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444575/ Huang et al. 2019 (ESWN 01)] | ||
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#IRIS|IRIS]] | |[[#IRIS|IRIS]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS |
Revision as of 01:48, 16 December 2021
Page editor | Section editor | ||
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Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL |
Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
Please be aware that some regimens listed here are studies for gastric cancer, not esophageal cancer, reflecting the overlap between treatments of esophageal and gastric cancer.
There are several related dedicated pages:
- Histology-specific:
- Biomarker-specific:
56 regimens on this page
74 variants on this page
|
Guidelines
ASCO
- 2020: Shah et al. Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline
ESMO
- 2016: Lordick et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
NCCN
Neoadjuvant induction therapy
Capecitabine & Cisplatin (CX)
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CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Lee et al. 2007esoph | Retrospective |
The study was for patients with stage IV disease.
Patients 97% adenocarcinoma, 3% squamous cell histology; 3% with ECOG PS of 2.
- Patients with M1b disease (visceral metastases) received the chemotherapy only part until progression of disease or unacceptable toxicity.
- Patients with M1a or M1b (non-viscertal metastases) received 2 cycles of the chemotherapy only part, underwent treatment with chemoradiation, and then treatment continued with--presumably, but not outright specified in the paper--chemotherapy only until progression of disease or unacceptable toxicity.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Cisplatin (Platinol) 60 mg/m2 IV over 60 minutes once on day 1, given first
21-day cycles
Subsequent treatment
- Patients with M1a or M1b disease: Definitive capecitabine, cisplatin, RT
References
- Retrospective: Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007 Nov;37(11):829-35. Epub 2007 Oct 19. link to original article contains verified protocol PubMed
Cisplatin & Docetaxel (DC)
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ruhstaller et al. 2009 (SAKK 75/02) | 2003-2006 | Phase II | ||
Ruhstaller et al. 2018 (SAKK 75/08) | 2010-2013 | Phase 3 (C) | Cisplatin, Docetaxel, Cetuximab | Did not meet primary endpoint of PFS |
SAKK 75/02 patients: 55% adenocarcinoma, 45% squamous cell histology
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 2 cycles
Subsequent treatment
References
- SAKK 75/02: Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, von Moos R, Borner M, Pestalozzi BC, Balmermajno S, Köberle D, Terraciano L, Schnider A, Bodis S, Popescu R; Swiss Group for Clinical Cancer Research. Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009 Sep;20(9):1522-8. Epub 2009 May 22. link to original article contains verified protocol PubMed
- SAKK 75/08: Ruhstaller T, Thuss-Patience P, Hayoz S, Schacher S, Knorrenschild JR, Schnider A, Plasswilm L, Budach W, Eisterer W, Hawle H, Mariette C, Hess V, Mingrone W, Montemurro M, Girschikofsky M, Schmidt SC, Bitzer M, Bedenne L, Brauchli P, Stahl M; Swiss Group for Clinical Cancer Research; German Esophageal Cancer Study Group; Arbeitsgemeinschaft Medikamentöse Tumortherapie; Fédération Francophone de Cancérologie Digestive. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08). Ann Oncol. 2018 Jun 1;29(6):1386-1393. link to original article PubMed NCT01107639
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol (Cisplatin)
Regimen variant #1, 80/4000, 4 day 5-FU infusion
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Girling et al. 2002 (UK MRC OE02) | 1992-1998 | Phase 3 (E-esc) | Surgery alone | Seems to have superior OS1 |
1Reported efficacy for UK MRC OE02 is based on the 2009 update.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycle for 2 cycles
Subsequent treatment
Regimen variant #2, 80/4000, 5 day 5-FU infusion
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ando et al. 2011 (JCOG 9907) | 2000-2006 | Phase 3 (E-switch-ic) | Adjuvant CF | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycle for 2 cycles
Subsequent treatment
Regimen variant #3, 100/5000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kelsen et al. 1998 (RTOG 8911) | 1990-1995 | Phase 3 (E-esc) | Surgery alone | Did not meet primary endpoint of OS |
Ancona et al. 2001 | 1992-1997 | Phase 3 (E-esc) | Surgery alone | Did not meet primary endpoint of OS |
Note: it is not entirely clear from Ancona et al. 2001 whether this was a 96-hour or 120-hour infusion; there was option to proceed after the 2nd cycle. In both trials, this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Ancona et al. 2001 patients: 100% squamous cell carcinoma histology
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: see note)
28-day cycle for 3 cycles
Subsequent treatment
- RTOG 8911: Surgery, then adjuvant CF
- Ancona et al. 2001: Surgery, performed 3 to 4 weeks after the last cycle of chemotherapy
References
- RTOG 8911: Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. link to original article contains verified protocol PubMed
- Update: Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Ajani JA, Kocha W, Minsky BD, Roth JA, Willett CG; Radiation Therapy Oncology Group; USA Intergroup. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007 Aug 20;25(24):3719-25. link to original article PubMed
- Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001 Jun 1;91(11):2165-74. link to original article contains partial protocol PubMed NCT00002897
- UK MRC OE02: Girling DJ, Bancewicz J, Clark PI, Smith DB, Donnelly RJ, Fayers PM, Weeden S, Hutchinson T, Harvey A, Lyddiard J; Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1727-33. link to original article contains protocol PubMed
- Update: Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009 Oct 20;27(30):5062-7. Epub 2009 Sep 21. link to original article PubMed
- JCOG 9907: Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, Ikeda K, Kanda T, Tsujinaka T, Nakamura K, Fukuda H. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012 Jan;19(1):68-74. Epub 2011 Aug 31. link to original article contains verified protocol PubMed NCT00190554
Cisplatin & Irinotecan (IC)
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IC: Irinotecan & Cisplatin
Regimen
Study | Evidence |
---|---|
Ilson et al. 2011 | Phase II |
Illson et al. patients: 75% adenocarcinoma, 22% squamous cell, 3% poorly differentiated history; 33% gastroesophageal junction.
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
- Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
Supportive medications
- Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1 & 8, prior to chemotherapy
- One of the following:
- Granisetron 2 mg PO once per day on days 1 & 8, prior to chemotherapy
- Ondansetron (Zofran) 32 mg IV once per day on days 1 & 8, prior to chemotherapy
- At least 500 mL D5NS or NS as supportive hydration
- Atropine (Atropen) 0.5 to 1 mg IV prn cholinergic symptoms
21-day cycle for 2 cycles
Subsequent treatment
References
- Ilson DH, Minsky BD, Ku GY, Rusch V, Rizk N, Shah M, Kelsen DP, Capanu M, Tang L, Campbell J, Bains M. Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer. 2011 Oct 11. link to original article contains verified protocol PubMed
EOF
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EOF: Epirubicin, Oxaliplatin, Fluorouracil
Regimen
Note: This regimen is sometimes listed as a perioperative option, but it is not clearly described as one by the primary reference to the REAL-2 study. Study participants could have had either locally advanced or metastatic disease, and the primary reference did not list a uniform policy about what patients underwent surgery and its timing--although a few patients were mentioned to undergo surgery.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
Supportive medications
- Dexamethasone (Decadron) 8 mg IV once on day 1, prior to chemotherapy, then 4 mg PO three times per day on days 2 & 3
- 5-HT3 antagonist once on day 1, prior to chemotherapy
- Metoclopramide (Reglan) 10 mg PO three times per day on days 2 to 4
- Warfarin (Coumadin) 1 mg PO once per day as thrombosis prophylaxis, started on day -1
21-day cycle for up to 8 cycles; for perioperative use per some guidelines, 3 cycles preoperatively and 3 cycles postoperatively would be used
EOX
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EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)
EOC: Epirubicin, Oxaliplatin, Capecitabine
Regimen
Note: This regimen is sometimes listed as a perioperative option, but it is not clearly described as one by the primary reference to the REAL-2 study. Study participants could have had either locally advanced or metastatic disease, and the primary reference did not list a uniform policy about what patients underwent surgery and its timing--although a few patients were mentioned to undergo surgery.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 500 to 625 mg/m2 PO twice per day on days 1 to 21
Supportive medications
- Dexamethasone (Decadron) 8 mg IV once on day 1, prior to chemotherapy, then 4 mg PO three times per day on days 2 & 3
- 5-HT3 antagonist once on day 1, prior to chemotherapy
- Metoclopramide (Reglan) 10 mg PO three times per day on days 2 to 4
21-day cycle for up to 8 cycles; for perioperative use per some guidelines, 3 cycles preoperatively and 3 cycles postoperatively would be used
FLEP
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FLEP: Fluorouracil, Leucovorin, Etoposide, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Stahl et al. 2005 | Non-randomized portion of RCT |
For historic reference.
Chemotherapy
Subsequent treatment
- PE & RT (40 Gy), then surgery versus PE & RT (at least 65 Gy)
References
- Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, Klump B, Budach W, Teichmann R, Schmitt M, Schmitt G, Franke C, Wilke H. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005 Apr 1;23(10):2310-7. Erratum in: J Clin Oncol. 2006 Jan 20;24(3):531. link to original article PubMed
PCF
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PCF: Paclitaxel, Cisplatin, Fluorouracil
Regimen
Study | Evidence |
---|---|
Zhao et al. 2015 (ZY-01) | Non-randomized portion of RCT |
Chemotherapy
- Paclitaxel (Taxol) 100 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 2
- Fluorouracil (5-FU) 700 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3500 mg/m2)
2 cycles
Subsequent treatment
- Surgery, then adjuvant PCF x 2 versus no further treatment
References
- ZY-01: Zhao Y, Dai Z, Min W, Sui X, Kang H, Zhang Y, Ren H, Wang XJ. Perioperative versus Preoperative Chemotherapy with Surgery in Patients with Resectable Squamous Cell Carcinoma of Esophagus: A Phase III Randomized Trial. J Thorac Oncol. 2015 Sep;10(9):1349-1356. link to original article contains protocol PubMed NCT01225523
Neoadjuvant chemoradiotherapy
Note: while these regimens are listed as neoadjuvant (pre-operative), in some cases they are also used as definitive therapy in patients that are not surgical candidates.
Capecitabine, Carboplatin, Paclitaxel, RT
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Capecitabine, Carboplatin, Paclitaxel, RT: Capecitabine, Carboplatin, Paclitaxel, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Czito et al. 2006 | Pilot, <20 pts |
The primary reference did not specify whether patients were intended to proceed to surgery.
Patients: 77% adenocarcinoma, 23% squamous cell histology. 54% lower thoracic, 23% midthoracic, 23% gastroesophageal junction.
Chemotherapy
- Carboplatin (Paraplatin) AUC 1.5 IV once per day on days 2, 9, 16, 23, 30
- Paclitaxel (Taxol) 45 mg/m2 IV over 60 minutes once per day on days 2, 9, 16, 23, 30
- Capecitabine (Xeloda) 600 mg/m2 PO twice per day, starting on day 1 and finishing the evening of the last day of radiation therapy
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions, for a total dose of 50.4 Gy
6-week course
Subsequent treatment
- Patients were evaluated for surgery, performed 6 to 8 weeks after chemoradiotherapy completion. Patients could receive adjuvant chemotherapy, beginning 4 to 12 weeks postoperatively
References
- Phase I: Czito BG, Kelsey CR, Hurwitz HI, Willett CG, Morse MA, Blobe GC, Fernando NH, D'Amico TA, Harpole DH, Honeycutt W, Yu D, Bendell JC. A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):1002-7. Epub 2006 Dec 29. link to original article contains verified protocol PubMed
Capecitabine, Cisplatin, RT
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CX & RT: Cisplatin, Xeloda (Capecitabine), Radiation Therapy
Regimen
Note: This study was for patients with stage IV disease. Please reference the original paper, as there were no patients who only received this neoadjuvant treatment, and they did not undergo surgical resection of disease.
Patients: 3% adenocarcinoma, 97% squamous cell histology; 3% with ECOG PS of 2.
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV over 60 minutes once on day 1, given first
- Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5, given second
7-day cycles until radiation therapy is complete
Radiotherapy
- Concurrent radiation therapy, total of 54 Gy given (dose per fraction and total duration of treatment was not specified)
One course
References
- Retrospective: Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007 Nov;37(11):829-35. Epub 2007 Oct 19. link to original article contains verified protocol--please see note above, as patients in this study did not undergo surgery PubMed
Capecitabine, Docetaxel, RT
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Capecitabine, Docetaxel, RT: Capecitabine, Docetaxel, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Wood et al. 2013 (D-9939) | Phase 1 |
Note: Some guidelines recommend different dosing but this is the only publication that we could locate with dosing details. Treatment is assumed to begin on a Monday.
Chemotherapy
- Docetaxel (Taxotere) 15 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 3500 mg PO once per day on days 1 to 5, given prior to radiation
7-day cycle for 5 cycles
Radiotherapy
- Concurrent radiation therapy to 50.4 Gy in 28 fractions
5-week course
References
- Phase 1: Wood MD, Zaki BI, Gordon SR, Sutton JE Jr, Lisovsky M, Gui J, Bubis JA, Dragnev KH, Rigas JR. Trimodality therapy for stage II-III carcinoma of the esophagus: a dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy. J Thorac Oncol. 2013 Apr;8(4):487-94. link to original article link to PMC article contains verified protocol PubMed NCT00153881
Capecitabine, Docetaxel, Oxaliplatin, RT
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Capecitabine, Docetaxel, Oxaliplatin, RT: Capecitabine, Docetaxel, Oxaliplatin, Radiation Therapy
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Spigel et al. 2010 (SCRI GI 57) | 2005-2008 | Phase I/II |
Patients: 69% adenocarcinoma, 18% squamous cell, 12% not otherwise specified. 69% distal esophagus, 16% midesophagus, 14% gastroesophageal junction.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 7, 15 to 21, 29 to 35
- Docetaxel (Taxotere) 20 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29
- Oxaliplatin (Eloxatin) 40 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29
Supportive medications
- Dexamethasone (Decadron) 4 mg PO every 12 hours before, at the time of, and after Docetaxel (Taxotere); first dose the evening before Docetaxel (Taxotere)
- "Routine antiemetics"
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy
5-week course
Subsequent treatment
- Endoscopy, CT scan, and--if available--endoscopic ultrasound for restaging 2 to 4 weeks after finishing chemoradiation, with subsequent treatment as follows:
- Appropriate candidates: Surgical resection sometime during weeks 9 to 12
- Patients who were no longer surgical candidates: Additional radiation therapy to a total dose of 64.8 Gy
References
- SCRI GI 57: Spigel DR, Greco FA, Meluch AA, Lane CM, Farley C, Gray JR, Clark BL, Burris HA 3rd, Hainsworth JD. Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. J Clin Oncol. 2010 May 1;28(13):2213-9. Epub 2010 Mar 29. link to original article contains verified protocol PubMed NCT00193128
Capecitabine, Oxaliplatin, RT
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CapeOx & RT: Capecitabine, Oxaliplatin, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Javle et al. 2009 | Phase I |
Chemotherapy
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once per day on days 1, 15, 29
Radiotherapy
- Concurrent radiation therapy, total dose of 50.4 Gy
5-week course
Subsequent treatment
References
- Phase I: Javle MM, Yang G, Nwogu CE, Wilding GE, O'Malley L, Vinjamaram S, Schiff MD, Nava HR, LeVea C, Clark KR, Prey JD, Smith PF, Pendyala L. Capecitabine, oxaliplatin and radiotherapy: a phase IB neoadjuvant study for esophageal cancer with gene expression analysis. Cancer Invest. 2009 Feb;27(2):193-200. link to original article contains protocol PubMed
Capecitabine, Paclitaxel, RT
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Capecitabine, Paclitaxel, RT: Capecitabine, Paclitaxel, Radiation Therapy
Regimen
Chemotherapy
- Capecitabine (Xeloda) 625 to 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Paclitaxel (Taxol) 45 to 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy not defined
5-week course
References
- No primary reference could be found for this regimen.
Carboplatin, Fluorouracil, RT
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Carboplatin, Fluorouracil, RT: Carboplatin, Fluorouracil, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Zemanoa et al. 2009 | Non-randomized |
Patients: 86% squamous cell, 8% adenocarcinoma, 6% other histology. 3% ECOG PS of 2.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
21-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy.
- If surgery was contraindicated, total dose was increased to 50.4 to 56.8 Gy.
42-day course
Subsequent treatment
- Upper endoscopy and CT chest and abdomen was performed after completion of chemoradiation
- Surgery planned to be done 4 to 6 weeks after finishing chemoradiation
References
- Zemanova M, Petruzelka L, Pazdro A, Kralova D, Smejkal M, Pazdrova G, Honova H. Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-up. Dis Esophagus. 2010 Feb;23(2):160-7. Epub 2009 Jun 9. link to original article contains verified protocol PubMed
Carboplatin & Paclitaxel (CP) & RT
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CP & RT: Carboplatin, Paclitaxel, Radiation Therapy
ESMO-preferred for squamous cell carcinoma (I-A, 2016) |
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Meerten et al. 2006 | 2001-2004 | Phase II | ||
van Hagen et al. 2012 (CROSS) | 2004-2008 | Phase 3 (E-esc) | Surgery alone | Superior OS1 10-year OS: 38% vs 25% (HR 0.70, 95% CI 0.55-0.89) |
1Reported efficacy is based on the 2021 update.
van Meerten et al. Patients: 76% adenocarcinoma, 22% squamous cell, 2% large cell histology. 91% lower esophagus, 9% thoracic esophagus
CROSS patients: 75% adenocarcinoma, 23% squamous cell, 2% other. 24% gastroesophageal junction
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15, 22, 29, given second
- Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, given first
Supportive medications
- Dexamethasone (Decadron) 10 mg IV once per day on days 1, 8, 15, 22, 29; 30 minutes prior to Paclitaxel (Taxol)
- Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15, 22, 29; 30 minutes prior to Paclitaxel (Taxol)
- Clemastine (Tavist) 2 mg IV once per day on days 1, 8, 15, 22, 29; 30 minutes prior to Paclitaxel (Taxol)
- Between paclitaxel & carboplatin: 100 mL NS given over 30 minutes, then Ondansetron (Zofran) 8 mg in 100 mL NS given over 30 minutes
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 23 fractions, for a total dose of 41.4 Gy
5-week course
Subsequent treatment
- Surgery planned to be done within 6 weeks of finishing chemoradiation; van Hagen et al. 2012 said surgery was done as soon as possible after finishing chemoradiotherapy, preferably within 4 to 6 weeks
References
- van Meerten E, Muller K, Tilanus HW, Siersema PD, Eijkenboom WM, van Dekken H, Tran TC, van der Gaast A. Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study. Br J Cancer. 2006 May 22;94(10):1389-94. link to original article contains verified protocol link to PMC article contains verified protocol PubMed
- CROSS: van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. link to original article contains verified protocol link to appendix with details about administration PubMed NTR487
- Update: Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. Epub 2015 Aug 5. link to original article PubMed
- Update: Eyck BM, van Lanschot JJB, Hulshof MCCM, van der Wilk BJ, Shapiro J, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch OR, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Spillenaar Bilgen EJ, van der Sangen MJC, Rozema T, Ten Kate FJW, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS Study Group. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol. 2021 Jun 20;39(18):1995-2004. Epub 2021 Apr 23. link to original article PubMed
Cisplatin, Docetaxel, RT
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DC & RT: Docetaxel, Cisplatin, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Ruhstaller et al. 2009 (SAKK 75/02) | Phase II |
Patients: 55% adenocarcinoma, 45% squamous cell histology
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Docetaxel (Taxotere) 20 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy
5-week course
Subsequent treatment
- Surgery, 3 to 8 weeks after finishing chemoradiation
References
- SAKK 75/02: Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, von Moos R, Borner M, Pestalozzi BC, Balmermajno S, Köberle D, Terraciano L, Schnider A, Bodis S, Popescu R; Swiss Group for Clinical Cancer Research. Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009 Sep;20(9):1522-8. Epub 2009 May 22. link to original article contains verified protocol PubMed
Cisplatin & Fluorouracil (CF) & RT
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CF & RT: Cisplatin, Fluourouracil, Radiation Therapy
Regimen variant #1, 75/3200 x 2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mariette et al. 2014 (FFCD 9901) | 2000-2009 | Phase 3 (E-esc) | Surgery alone | Did not meet primary endpoint of OS |
Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on either day 1 or 2
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 3200 mg/m2)
28-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy
5-week course
Subsequent treatment
Regimen variant #2, 75/4000 x 2
Study | Evidence |
---|---|
Bedenne et al. 2007 (FFCD 9102) | Non-randomized portion of RCT |
Patients: 89% epidermoid, 11% glandular histology.
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
Supportive medications
- 1 liter NS IV over 2 hours before and after Cisplatin (Platinol)
21-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 23 fractions, for a total dose of 46 Gy
- Earlier in the study, some patients instead received split-course radiation therapy, 3 Gy fractions x 5 fractions given on days 1 to 5. 15 Gy per cycle; total dose after 2 cycles is 30 Gy.
4.5-week course
Subsequent treatment
- Cisplatin, Fluorouracil, RT (no surgery) x 3 (5 cycles total) versus surgery, 50 to 60 days after start of chemoradiation
Regimen variant #3, 80/3200
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burmeister et al. 2005 | 1994-2000 | Phase 3 (E-esc) | Surgery alone | Did not meet primary endpoint of PFS |
Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 3200 mg/m2)
Radiotherapy
- Concurrent radiation therapy, 2.33 Gy fractions x 15 fractions for a total dose of 35 Gy
3-week course
Subsequent treatment
Regimen variant #4, 100/4000 x 2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tepper et al. 2008 (CALGB 9781) | 1997-2000 | Phase 3 (E-esc) | Surgery alone | Superior OS |
Patients: 75% adenocarcinoma, 25% squamous cell histology. 5% with ECOG PS of 2.
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 30 minutes once on day 1, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1, given second (total dose per cycle: 4000 mg/m2)
28-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, then a 5.4 Gy final boost, for a total dose of 50.4 Gy, starting within 24 hours of start of chemotherapy
5-week course
Subsequent treatment
- EGD and CT chest and abdomen done within 4 weeks after finishing radiation therapy. Only patients who still had resectable disease that was stable or responded would proceed to surgery. Surgery was planned to be done 3 to 8 weeks after finishing chemoradiation.
References
- Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, Ackland S, Gotley DC, Joseph D, Millar J, North J, Walpole ET, Denham JW; Trans-Tasman Radiation Oncology Group; Australasian Gastro-Intestinal Trials Group. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005 Sep;6(9):659-68. link to original article contains protocol PubMed
- FFCD 9102: Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, Pezet D, Roullet B, Seitz JF, Herr JP, Paillot B, Arveux P, Bonnetain F, Binquet C. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007 Apr 1;25(10):1160-8. link to original article contains verified protocol PubMed
- CALGB 9781: Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008 Mar 1;26(7):1086-92. link to original article contains verified protocol link to PMC article PubMed NCT00003118
- FFCD 9901: Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014 Aug 10;32(23):2416-22. Epub 2014 Jun 30. link to original article PubMed NCT00047112
Cisplatin, Irinotecan, RT
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Cisplatin, Irinotecan, RT: Cisplatin, Irinotecan, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Ilson et al. 2011 | Phase II |
Patients: 75% adenocarcinoma, 22% squamous cell, 3% poorly differentiated history; 33% gastroesophageal junction.
Preceding treatment
- IC induction x 2
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
- Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
21-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions, for a total of 50.4 Gy
5.5-week course
Subsequent treatment
- Surgery, performed 4 to 8 weeks after chemoradiation
References
- Ilson DH, Minsky BD, Ku GY, Rusch V, Rizk N, Shah M, Kelsen DP, Capanu M, Tang L, Campbell J, Bains M. Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer. 2011 Oct 11. link to original article contains verified protocol PubMed
Cisplatin, Paclitaxel, RT
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Cisplatin, Paclitaxel, RT: Cisplatin, Paclitaxel, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Urba et al. 2003 | Phase II |
Patients: 83% adenocarcinoma, 14% squamous cell, 3% undifferentiated histology
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1
- Paclitaxel (Taxol) 60 mg/m2 IV over 3 hours once per day on days 1, 8, 15, 22
Supportive medications
- Dexamethasone (Decadron) 20 mg PO twice per day on days 1, 8, 15, 22; 12 and 6 hours before Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22; 30 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15, 22; 30 minutes prior to Paclitaxel (Taxol)
- 1 liter D5NS and mannitol 12.5 g bolus IV once on day 1, prior to Cisplatin (Platinol)
- Mannitol 25 g in 1 liter D5NS IV over 4 hours once on day 1, after Cisplatin (Platinol)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 23, continuing until ANC greater than 10,000/uL
Radiotherapy
- Concurrent radiation therapy, 1.5 Gy fractions given twice per day on days 1 to 5, 8 to 12, 15 to 19, with at least 6 hours between fractions, for a total dose of 45 Gy
4-week course
Subsequent treatment
- Barium swallow and CT chest and abdomen done about 1 week prior to surgery to rule out metastatic disease. Surgery to be done on approximately day 50
References
- Urba SG, Orringer MB, Ianettonni M, Hayman JA, Satoru H. Concurrent cisplatin, paclitaxel, and radiotherapy as preoperative treatment for patients with locoregional esophageal carcinoma. Cancer. 2003 Nov 15;98(10):2177-83. link to original article contains verified protocol PubMed
Cisplatin, Vinorelbine, RT
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Cisplatin, Vinorelbine, RT: Cisplatin, Vinorelbine, Radiation Therapy
Regimen variant #1, standard cisplatin
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2018 (NEOCRTEC5010) | 2007-2014 | Phase 3 (E-esc) | No neoadjuvant therapy | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 20 fractions, for a total dose of 40 Gy
4-week course
Subsequent treatment
Regimen variant #2, split-dose cisplatin
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2018 (NEOCRTEC5010) | 2007-2014 | Phase 3 (E-esc) | No neoadjuvant therapy | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 4
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 20 fractions, for a total dose of 40 Gy
4-week course
Subsequent treatment
References
- NEOCRTEC5010: Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus (NEOCRTEC5010): a phase III multicenter, randomized, open-label clinical trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. Epub 2018 Aug 8. link to original article link to PMC article PubMed NCT01216527
Docetaxel, Fluorouracil, RT
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Docetaxel, Fluorouracil, RT: Docetaxel, Fluorouracil, Radiation Therapy
Regimen variant #1, 15/4000 x 2
Study | Evidence |
---|---|
Hihara et al. 2007 | Phase II |
Patients: 86% squamous cell, 14% carcinosarcoma histology
Chemotherapy
- Docetaxel (Taxotere) 7.5 mg/m2 IV over 60 minutes once per day on days 1 & 8
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15 (total dose per cycle: 4000 mg/m2)
Supportive medications
- Dexamethasone (Decadron) 8 mg IV once per day on days 1 & 8; 30 minutes prior to Docetaxel (Taxotere)
28-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 30 to 33 fractions, for a total dose of 60 to 66 Gy
6- to 6.5-week course
Regimen variant #2
Note: No primary reference could be found for this regimen.
Chemotherapy
- Docetaxel (Taxotere) 20 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 to 300 mg/m2/day IV continuous infusion over 120 hours, started on day 1
Radiotherapy
- Concurrent radiation therapy not defined
7-day cycle for 5 cycles
References
- Phase I: Hihara J, Yoshida K, Hamai Y, Emi M, Yamaguchi Y, Wadasaki K. Phase I study of docetaxel (TXT) and 5-fluorouracil (5-FU) with concurrent radiotherapy in patients with advanced esophageal cancer. Anticancer Res. 2007 Jul-Aug;27(4C):2597-603. link to original article contains verified protocol PubMed
Fluorouracil, Oxaliplatin, RT
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Fluorouracil, Oxaliplatin, RT: Fluorouracil, Oxaliplatin, Radiation Therapy
Regimen variant #1, 50.4 Gy, bi-weekly oxaliplatin
Study | Evidence |
---|---|
Khushalani et al. 2002 | Phase II |
58% patients were classified as stage IV disease
Chemotherapy
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once per day on days 1, 15, 29
- Fluorouracil (5-FU) 180 mg/m2/day IV continuous infusion over 35 days, started on day 8 (total dose: 6300 mg/m2)
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 20 to 22 fractions, for an initial total dose of 36 to 39.6 Gy, started on day 8
- Followed by off-cord conformal oblique fields, 5.4 to 9 Gy given to the clinical target volume (CTV). A second off-cord phase to the gross tumor volume (GTV) of 5.4 Gy was then given, for a total dose delivered of 50.4 Gy to the GTV.
6-week course
Subsequent treatment
- Upper GI endoscopy and CT chest, abdomen, and pelvis were done after completion of chemoradiation, and patients without progressive stage II-III disease were offered surgery followed by another cycle of oxaliplatin and 5-FU. Patients who could not proceed to surgery were given another 1 to 2 cycles of oxaliplatin and 5-FU within 2 weeks.
Regimen variant #2, 50.4 Gy, weekly oxaliplatin
Study | Years of enrollment | Evidence |
---|---|---|
Ajani et al. 2013 (MDACC 2004-0703) | 2005-2011 | Non-randomized portion of RCT |
Note: it is unclear how long the 5-FU continuous infusions were in this regimen; the authors have been contacted for clarification. Treatment is assumed to start on a Monday.
Preceding treatment
- FUOX versus no induction chemotherapy
Chemotherapy
- Oxaliplatin (Eloxatin) 40 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1000 mg/m2)
7-day cycle for 5 cycles
Radiotherapy
- Concurrent radiation therapy: 50.4 Gy of proton or photon (intensity modulated) radiation in 28 fractions
5-week course
Subsequent treatment
References
- Khushalani NI, Leichman CG, Proulx G, Nava H, Bodnar L, Klippenstein D, Litwin A, Smith J, Nava E, Pendyala L, Smith P, Greco W, Berdzik J, Douglass H, Leichman L. Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer. J Clin Oncol. 2002 Jun 15;20(12):2844-50. link to original article contains verified protocol PubMed
- MDACC 2004-0703: Ajani JA, Xiao L, Roth JA, Hofstetter WL, Walsh G, Komaki R, Liao Z, Rice DC, Vaporciyan AA, Maru DM, Lee JH, Bhutani MS, Eid A, Yao JC, Phan AP, Halpin A, Suzuki A, Taketa T, Thall PF, Swisher SG. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013 Nov;24(11):2844-9. Epub 2013 Aug 23. link to original article link to PMC article contains verified protocol PubMed NCT00525915
Definitive therapy
Capecitabine, Cisplatin, RT
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CX & RT: Cisplatin, Xeloda (Capecitabine), Radiation Therapy
Regimen variant #1, 1250/60/50
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Crosby et al. 2013 (SCOPE-1) | 2008-2012 | Phase 3 (C) | Capecitabine, Cisplatin, Cetuximab, RT | Did not meet primary endpoint of OS1 |
1Reported efficacy is based on the 2017 update.
Patients: 25% adenocarcinoma, 73% squamous cell, 2% undifferentiated histology
Chemotherapy
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 21
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Radiotherapy
- Concurrent radiation therapy, total of 50 Gy given in 25 fractions with cycles 3 & 4
5-week course
Regimen variant #2, 1600/30/54
Study | Evidence |
---|---|
Lee et al. 2007esoph | Retrospective |
Patients: 97% adenocarcinoma, 3% squamous cell histology; 3% with ECOG PS of 2.
The study was for patients with stage IV disease.
- Patients with M1b disease (visceral metastases) received the chemotherapy only part until progression of disease or unacceptable toxicity.
- Patients with M1a or M1b (non-visceral metastases) received 2 cycles of the chemotherapy only part, underwent treatment with chemoradiation, and then treatment continued with--presumably, but not outright specified in the paper--chemotherapy only until progression of disease or unacceptable toxicity.
Preceding treatment
- XP x 2
Chemotherapy
- Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5
- Cisplatin (Platinol) 30 mg/m2 IV over 60 minutes once on day 1, given first
7-day cycles until radiation therapy is complete
Radiotherapy
- Concurrent radiation therapy, total of 54 Gy given. Dose per fraction and total duration of treatment were not specified, but based on other regimens, it is suspected to be either 1.8 Gy x 30 fractions or 2 Gy x 27 fractions.
One course
References
- Retrospective: Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007 Nov;37(11):829-35. Epub 2007 Oct 19. link to original article contains verified protocol PubMed
- SCOPE-1: Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, Ray R, Bashir N, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013 Jun;14(7):627-37. link to original article contains verified protocol PubMed ISRCTN47718479
- Update: Crosby T, Hurt CN, Falk S, Gollins S, Staffurth J, Ray R, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G, Mukherjee S. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer. Br J Cancer. 2017 Mar 14;116(6):709-716. Epub 2017 Feb 14. link to original article contains verified protocol link to PMC article contains verified protocol PubMed
Cisplatin, Docetaxel, RT
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DC & RT: Docetaxel, Cisplatin, Radiation Therapy
Regimen variant #1
Study | Evidence |
---|---|
Day et al. 2010 | Phase I |
Patients: 46% squamous cell, 54% adenocarcinoma histology
Note: some guidelines suggest a wider dose range of 20 to 30 mg/m2 for both cisplatin and docetaxel. The primary reference also investigated these dose levels, but ultimately recommended 30 mg/m2 dosages for both cisplatin and docetaxel.
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Docetaxel (Taxotere) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Supportive medications
- "Steroid and anti-emetic pre-medication"
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 25 fractions, for a total dose of 50 Gy, to start within 4 hours after the first dose of chemotherapy.
5-week course
References
- Phase I: Day FL, Leong T, Ngan S, Thomas R, Jefford M, Zalcberg JR, Rischin D, McKendick J, Milner AD, Di Iulio J, Matera A, Michael M. Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer. Br J Cancer. 2011 Jan 18;104(2):265-71. Epub 2010 Dec 14. link to original article contains verified protocol link to PMC article PubMed
Cisplatin & Fluorouracil (CF) & RT
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CF & RT: Cisplatin, Fluorouracil, Radiation Therapy
FP & RT: Fluorouracil, Platinol (Cisplatin), Radiation Therapy
Regimen variant #1, 60/4725 x 4 (50 Gy)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Crosby et al. 2013 (SCOPE-1) | 2008-2012 | Phase 3 (C) | Capecitabine, Cisplatin, Cetuximab, RT | Did not meet primary endpoint of OS1 |
1Reported efficacy is based on the 2017 update.
Note: This regimen was an alternative for patients who could not swallow pills.
Patients: 25% adenocarcinoma, 73% squamous cell, 2% undifferentiated histology
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4725 mg/m2)
21-day cycle for 4 cycles
Radiotherapy
- Concurrent radiation therapy, total of 50 Gy given in 25 fractions with cycles 3 & 4
5-week course
Regimen variant #2, 75/4000 x 2 (50.4 Gy)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Minsky et al. 2002 (RTOG 94-05) | 1995-1999 | Phase 3 (C) | Cisplatin, 5-FU, high-dose RT | Did not meet primary endpoint of OS24 |
Conroy et al. 2014 (PRODIGE5/ACCORD17) | 2004-2011 | Phase 3 (C) | See link | See link |
Patients: RTOG 94-05 included both adenocarcinoma and squamous cell histology
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
28-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy as follows:
- RTOG 94-05: 1.8 Gy fractions x 28 fractions, for a total dose of 50.4 Gy
- PRODIGE5/ACCORD17: 2 Gy fractions x 25 fractions, for a total dose of 50 Gy
5- to 5.5-week course
Subsequent treatment
Regimen variant #3, 75/4000 x 3 (66 Gy)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bedenne et al. 2007 (FFCD 9102) | 1993-2000 | Phase 3 (E-switch-ooc) | Surgery | Equivalent OS |
Patients: 89% epidermoid, 11% glandular histology. Note that this was not a formal non-inferiority study but the study met its primary endpoint of equivalence.
Preceding treatment
- CF & RT x 2
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV over 60 minutes once per day on days 1 to 5
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
Supportive medications
- 1 liter NS IV over 2 hours before and after Cisplatin (Platinol)
21-day cycle for 1 cycle, then 28-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 10 fractions, for a total dose of 66 Gy (including the initial 46 Gy)
- Earlier in the study, some patients instead received split-course radiation therapy
2-week course
Regimen variant #4, 75/4000 x 4 (50 Gy)
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Herskovic et al. 1992 (RTOG 85-01) | 1986-1990 | Phase 3 (E-esc) | Radiation therapy | Superior OS |
Patients: 88% squamous cell, 12% adenocarcinoma histology. 7% karnofsky performance scale of 50-60.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
28-day cycle for 1 cycle, then 21-day cycle for 3 cycles
Radiotherapy
- Concurrent radiation therapy: 2 Gy fractions x 15 fractions, then 2 Gy fractions x 10 fractions to the initial tumor length plus a 5 cm margin, for a total dose of 50.0 Gy
5-week course
References
- RTOG 85-01: Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11;326(24):1593-8. link to original article contains verified protocol PubMed
- Update: al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, Cooper J, Byhardt R, Davis L, Emami B. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol. 1997 Jan;15(1):277-84. link to original article contains verified protocol PubMed
- Update: Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL; Radiation Therapy Oncology Group. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999 May 5;281(17):1623-7. link to original article contains verified protocol PubMed
- RTOG 94-05: Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. link to original article contains verified protocol PubMed NCT00002631
- FFCD 9102: Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, Pezet D, Roullet B, Seitz JF, Herr JP, Paillot B, Arveux P, Bonnetain F, Binquet C. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007 Apr 1;25(10):1160-8. link to original article contains verified protocol PubMed
- SCOPE-1: Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, Ray R, Bashir N, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013 Jun;14(7):627-37. link to original article contains verified protocol PubMed ISRCTN47718479
- Update: Crosby T, Hurt CN, Falk S, Gollins S, Staffurth J, Ray R, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G, Mukherjee S. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer. Br J Cancer. 2017 Mar 14;116(6):709-716. Epub 2017 Feb 14. link to original article contains verified protocol link to PMC article contains verified protocol PubMed
- PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article contains protocol PubMed NCT00861094
- HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article PubMed
- KEYNOTE-975: NCT04210115
Cisplatin, Paclitaxel, RT
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TP & RT: Taxol (Paclitaxel), Platinol (Cisplatin), Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Suntharalingam et al. 2017 (RTOG 0436) | 2008-2013 | Phase 3 (C) | Cisplatin, Paclitaxel, Cetuximab, RT | Did not meet primary endpoint of OS |
Patients: 62% adenocarcinoma, 38% squamous cell histology. 14% with M1a disease. 6% with Zubrod PS score 2.
Chemotherapy
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions, for a total dose of 50.4 Gy
5-week course
References
- RTOG 0436: Suntharalingam M, Winter K, Ilson D, Dicker AP, Kachnic L, Konski A, Chakravarthy AB, Anker CJ, Thakrar H, Horiba N, Dubey A, Greenberger JS, Raben A, Giguere J, Roof K, Videtic G, Pollock J, Safran H, Crane CH. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: The NRG Oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol. 2017 Nov 1;3(11):1520-1528. link to original article contains verified protocol PubMed NCT00655876
FOLFOX4 & RT
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FOLFOX4 & RT: FOLinic acid, Fluorouracil, OXaliplatin, Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Conroy et al. 2014 (PRODIGE5/ACCORD17) | 2004-2011 | Phase 3 (E-switch-ic) | See link | See link |
Note: In contrast to the original reference, some guidelines list the dosage of leucovorin as 400 mg/m2. Despite being a non-superior experimental arm, this regimen is recommended by some guidelines such as ESMO.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1600 mg/m2 IV continuous infusion over 46 hours, given third (total dose per cycle: 2000 mg/m2)
- Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for 3 cycles
Radiotherapy
- Concurrent radiation therapy, 2 Gy fractions x 25 fractions, for a total dose of 50 Gy
5-week course
Subsequent treatment
- FOLFOX4 x 3
References
- PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article contains protocol PubMed NCT00861094
- HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article PubMed
- KEYNOTE-975: NCT04210115
Radiation therapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Herskovic et al. 1992 (RTOG 85-01) | 1986-1990 | Phase 3 (C) | Cisplatin, 5-FU, RT | Inferior OS |
Patients: 88% squamous cell, 12% adenocarcinoma histology. 7% Karnofsky performance scale of 50-60
Radiation as primary therapy; used as a comparator arm and here for reference purposes only.
Radiotherapy
- External beam radiotherapy total of 32 fractions: 50 Gy of regional treatment and 14 Gy to the boost field, for total dose of 64 Gy
6.4-week course
References
- RTOG 85-01: Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11;326(24):1593-8. link to original article contains verified protocol PubMed
- Update: al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, Cooper J, Byhardt R, Davis L, Emami B. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol. 1997 Jan;15(1):277-84. link to original article contains verified protocol PubMed
- Update: Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL; Radiation Therapy Oncology Group. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999 May 5;281(17):1623-7. link to original article contains verified protocol PubMed
Consolidation after definitive therapy
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin & Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Minsky et al. 2002 (RTOG 94-05) | 1995-1999 | Non-randomized portion of RCT | ||
Conroy et al. 2014 (PRODIGE5/ACCORD17) | 2004-2011 | Phase 3 (C) | See link | See link |
Patients: study included both adenocarcinoma and squamous cell histology
Preceding treatment
- RTOG 94-05: Definitive CF & RT versus definitive CF & high-dose RT
- PRODIGE5/ACCORD17: Definitive CF & RT
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
28-day cycle for 2 cycles
References
- RTOG 94-05: Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. link to original article contains verified protocol PubMed NCT00002631
- PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article contains protocol PubMed NCT00861094
- HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article PubMed
FOLFOX4
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FOLFOX4: FOLinic acid, Fluorouracil, OXaliplatin 4
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Conroy et al. 2014 (PRODIGE5/ACCORD17) | 2004-2011 | Phase 3 (E-switch-ic) | See link | See link |
Note: In contrast to the original reference, some guidelines list the dosage of leucovorin as 400 mg/m2. Despite being a non-superior experimental arm, this regimen is recommended by some guidelines such as ESMO.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1600 mg/m2 IV continuous infusion over 46 hours, given third (total dose per cycle: 2000 mg/m2)
- Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for 3 cycles
References
- PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article contains protocol PubMed NCT00861094
- HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article PubMed
Adjuvant therapy
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol
Regimen variant #1, 75/5000
Study | Years of enrollment | Evidence |
---|---|---|
Kelsen et al. 1998 (RTOG 8911) | 1990-1995 | Non-randomized portion of RCT |
Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant CF, then surgery
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: see note)
28-day cycle for 3 cycles
Regimen variant #2, 80/4000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ando et al. 2003 (JCOG 9204) | 1992-1997 | Phase 3 (E-esc) | Observation | Seems to have superior DFS |
Ando et al. 2011 (JCOG 9907) | 2000-2006 | Phase 3 (C) | Neoadjuvant CF | Seems to have inferior OS |
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycle for 2 cycles
References
- RTOG 8911: Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. link to original article contains verified protocol PubMed
- JCOG 9204: Ando N, Iizuka T, Ide H, Ishida K, Shinoda M, Nishimaki T, Takiyama W, Watanabe H, Isono K, Aoyama N, Makuuchi H, Tanaka O, Yamana H, Ikeuchi S, Kabuto T, Nagai K, Shimada Y, Kinjo Y, Fukuda H; JCOG. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study--JCOG9204. J Clin Oncol. 2003 Dec 15;21(24):4592-6. link to original article contains verified protocol PubMed
- JCOG 9907: Ando N, Kato H, Igaki H, Shinoda M, Ozawa S, Shimizu H, Nakamura T, Yabusaki H, Aoyama N, Kurita A, Ikeda K, Kanda T, Tsujinaka T, Nakamura K, Fukuda H. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol. 2012 Jan;19(1):68-74. Epub 2011 Aug 31. link to original article contains verified protocol PubMed NCT00190554
Nivolumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kelly et al. 2021 (CheckMate 577) | 2016-2019 | Phase 3 (E-RT-esc) | Placebo | Superior DFS |
Preceding treatment
- Neoadjuvant chemoradiotherapy (not specified), then Surgery, with residual pathologic disease
Immunotherapy
- Nivolumab (Opdivo) as follows:
- Cycles 1 to 8: 240 mg IV over 30 minutes once on day 1
- Cycles 9 to 17: 480 mg IV over 30 minutes once on day 1
14-day cycle for 8 cycles, then 28-day cycle for 9 cycles (1 year total)
References
- CheckMate 577: Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lièvre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. link to original article contains verified protocol PubMed NCT02743494
Metastatic or locally advanced disease, first-line
Carboplatin & Paclitaxel (CP)
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Regimen
Study | Evidence |
---|---|
Philip et al. 1997 | Phase II |
Note: In contrast to the original reference, some guidelines list the dosage of carboplatin as AUC 6.
Philip et al. Patients: locally advanced metastatic or recurrent esophageal or gastric cancer
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1, given second
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first
21-day cycles
References
- Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. contains protocol PubMed
Cisplatin & Fluorouracil (CF) & Pembrolizumab
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CF & Pembrolizumab: Cisplatin, Fluorouracil, Pembrolizumab
Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sun et al. 2021 (KEYNOTE-590) | 2017-2019 | Phase 3 (E-RT-esc) | CF | Superior OS Median OS: 12.4 vs 9.8 mo (HR 0.73, 95% CI 0.62-0.86) |
73% squamous histology.
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-590: Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. link to original article PubMed NCT03189719
Cisplatin & Irinotecan (IC)
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IC: Irinotecan & Cisplatin
CI: Cisplatin & Irinotecan
Regimen variant #1
Study | Evidence |
---|---|
Ilson 2004 | Phase II |
Note: In contrast to the original reference, some guidelines list cisplatin 25 mg/m2 as an alternate dosage.
Patients: 26% squamous cell, 74% adenocarcinoma histology. 85% metastatic disease.
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycles
Regimen variant #2
Study | Evidence |
---|---|
Ilson et al. 1999 | Phase II |
Patients: 66% adenocarcinoma, 34% squamous cell histology. Did not receive any prior chemotherapy. 97% with metastatic disease.
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV bolus once per day on days 1, 8, 15, 22
- Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22
Supportive medications
- Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22, prior to chemotherapy
- Granisetron 2 mg PO once per day on days 1, 8, 15, 22, prior to chemotherapy
- At least 500 mL D5NS IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, prior to Cisplatin (Platinol)
- Atropine (Atropen) used as pretreatment medication if there was diarrhea or abdominal cramps within 1 hour of Irinotecan (Camptosar)
42-day cycles
References
- Ilson DH, Saltz L, Enzinger P, Huang Y, Kornblith A, Gollub M, O'Reilly E, Schwartz G, DeGroff J, Gonzalez G, Kelsen DP. Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol. 1999 Oct;17(10):3270-5. link to original article contains verified protocol PubMed
- Ilson DH. Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. Oncology (Williston Park). 2004 Dec;18(14 Suppl 14):22-5. link to original article contains protocol PubMed
Cisplatin & Paclitaxel
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Regimen variant #1
Study | Evidence |
---|---|
Ilson et al. 2000 | Phase II |
Note: In contrast to the original reference, some guidelines list the paclitaxel dose as 135 mg/m2. No primary reference could be found for the 135 mg/m2 dosage. The protocol reported here was amended to change the original dose of 250 mg/m2 to 200 mg/m2 based on toxicity and treatment-related deaths.
Patients: 87% adenocarcinoma, 13% squamous cell histology. Included both gastroesophageal junction and esophageal patients. 95% with metastatic disease. None had received prior chemotherapy.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 2, given second
- Paclitaxel (Taxol) 200 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive medications
- "Granulocyte colony stimulating factor support"
21-day cycles
Regimen variant #2
Study | Evidence |
---|---|
Petrasch et al. 1998 | Phase II |
Patients: 25% adenocarcinoma, 75% squamous cell histology. Consisting of unresectable stage III disease, recurrent or metastatic tumors of esophageal origin.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 90 mg/m2 IV over 3 hours once on day 1, given first
Supportive medications
- Dexamethasone (Decadron) 20 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Clemastine (Tavist) 2 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- Ondansetron (Zofran) 8 mg IV once on day 1; 30 minutes prior to Paclitaxel (Taxol)
- "Adequate pre- and posthydration" for Cisplatin (Platinol)
14-day cycles
References
- Petrasch S, Welt A, Reinacher A, Graeven U, König M, Schmiegel W. Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. Br J Cancer. 1998 Aug;78(4):511-4. link to original article link to PMC article contains verified protocol PubMed
- Ilson DH, Forastiere A, Arquette M, Costa F, Heelan R, Huang Y, Kelsen DP. A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus. Cancer J. 2000 Sep-Oct;6(5):316-23. contains protocol PubMed
Docetaxel & Irinotecan
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Regimen
Study | Evidence |
---|---|
Burtness et al. 2009 | Phase II |
Patients: 79% adenocarcinoma, 21% squamous cell histology. All patients ECOG PS of 0 or 1, and unresectable/metastatic disease.
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV over 60 minutes once per day on days 1 & 8, given first
- Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
Supportive medications
- Dexamethasone (Decadron) as follows:
- 8 mg PO once per day on days 1 & 8; 12 hours before Docetaxel (Taxotere)
- 10 mg IV once per day on days 1 & 8, within 1 hour of chemotherapy
- 8 mg PO once per day on days 1 & 8; 12 hour afters chemotherapy
- Serotonin 5-HT3 antagonist IV once per day on days 1 & 8, within 1 hour before chemotherapy
- "Oral antiemetic therapy prescribed"
- Loperamide (Imodium) as needed
21-day cycles
References
- Burtness B, Gibson M, Egleston B, Mehra R, Thomas L, Sipples R, Quintanilla M, Lacy J, Watkins S, Murren JR, Forastiere AA. Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer. Ann Oncol. 2009 Jul;20(7):1242-8. Epub 2009 May 8. link to original article contains verified protocol link to PMC article PubMed
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ross et al. 2002 | 1995-1998 | Phase 3 (C) | MCF | Seems to have non-inferior OS |
Cunningham et al. 2008 (REAL-2) | 2000-2005 | Phase 3 (C) | 1. ECX | Non-inferior OS |
2. EOF | Non-inferior OS | |||
3. EOX | Seems to have inferior OS |
Ross et al. Patients: adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma histology, all advanced esophagogastric cancer.
REAL-2 Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV over 4 hours once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
Supportive medications
- (varied depending on reference):
- 3 liters per day "hyperhydration"
- 5-HT3 antagonist for emesis prophylaxis
- Growth factor support allowed, such as with Filgrastim (Neupogen)
- Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis
21-day cycle for up to 8 cycles
References
- Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. link to original article contains verified protocol PubMed
- REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed ISRCTN51678883
ECX
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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2008 (REAL-2) | 2000-2005 | Phase 3 (E-switch-ic) | 1. ECF | Non-inferior OS |
2. EOF 3. EOX |
Non-inferior OS |
REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV over 4 hours once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 21
21-day cycle for up to 8 cycles
References
- REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed ISRCTN51678883
EOF
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EOF: Epirubicin, Oxaliplatin, Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2008 (REAL-2) | 2000-2005 | Phase 3 (E-switch-ic) | 1. ECF 2. ECX |
Non-inferior OS |
3. EOX | Non-inferior OS |
Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
Supportive medications
- Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis
21-day cycle for up to 8 cycles
References
- REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed ISRCTN51678883
EOX
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EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)
EOC: Epirubicin, Oxaliplatin, Capecitabine
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2008 (REAL-2) | 2000-2005 | Phase 3 (E-switch-ic) | 1. ECF | Seems to have superior OS |
2. ECX | Non-inferior OS | |||
3. EOF | Non-inferior OS | |||
Waddell et al. 2013 (REAL3) | 2008-2011 | Phase 3 (C) | mEOC+P | Seems to have superior OS |
REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.
REAL3 patients: 99% adenocarcinoma, 1% undifferentiated histology. 39% esophagus, 31% gastroesophageal junction, 30% gastric. 6% ECOF PS of 2. 89% metastatic disease.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 21
21-day cycle for up to 8 cycles
References
- REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed content property of HemOnc.org ISRCTN51678883
- REAL3: Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. Epub 2013 Apr 15. link to original article contains verified protocol link to PMC article PubMed NCT00824785
mFOLFOX6 & Cetuximab
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mFOLFOX6 & Cetuximab: modified FOLinic acid, Fluorouracil, OXaliplatin, Cetuximab
FOLFOX-C: FOLinic acid, Fluorouracil, OXaliplatin, Cetuximab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Enziger et al. 2016 (CALGB 80403/ECOG E1206) | 2006-2009 | Randomized Phase II (E-switch-ic) | 1. ECF-C 2. IC-C |
Not powered to draw conclusions |
Patients: 91% adenocarcinoma, 9% squamous cell histology. 56% esophageal, 43% gastroesophageal tumors.
To receive full-dose therapy in this trial, patients were required to have an absolute neutrophil count of 1,000/µL or greater, platelets of 75,000/µL or greater, and no other grade 2 or higher treatment-related toxicity.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given third (total dose per cycle: 2800 mg/m2)
- Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given second, with oxaliplatin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given second, with leucovorin
Targeted therapy
- Cetuximab (Erbitux) as follows, given first:
- Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
- Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
References
- CALGB 80403/ECOG E1206: Enzinger PC, Burtness BA, Niedzwiecki D, Ye X, Douglas K, Ilson DH, Villaflor VM, Cohen SJ, Mayer RJ, Venook A, Benson AB 3rd, Goldberg RM. CALGB 80403 (Alliance)/E1206: a randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal junction cancers. J Clin Oncol. 2016 Aug 10;34(23):2736-42. Epub 2016 Jul 5. link to original article contains verified protocol link to PMC article PubMed NCT00381706
FULV & Gemcitabine
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FULV & Gemcitabine: 5-FU, LeucoVorin (Folinic acid), Gemcitabine
Regimen
Study | Evidence |
---|---|
Morgan-Meadows et al. 2005 | Phase II |
Patients: 100% esophageal cancer (both squamous and adenocarcinoma histology). Patients received no prior therapy.
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1, 8, 15 (total dose per cycle: 1800 mg/m2)
- Folinic acid (Leucovorin) 25 mg/m2 IV once per day on days 1, 8, 15
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Morgan-Meadows S, Mulkerin D, Berlin JD, Kim K, Bailey H, Saphner T, Jumonville A, Hansen R, Ahuja H, McFarland T, Thomas JP. A phase II trial of gemcitabine, 5-fluorouracil and leucovorin in advanced esophageal carcinoma. Oncology. 2005;69(2):130-4. Epub 2005 Aug 23. link to original article contains protocol PubMed
LdCF
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LdCF: Liposomal doxorubicin, Cisplatin, Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cascinu et al. 2010 | 2002-2005 | Randomized Phase II (E-switch-ic) | MCF | Seems to have superior OS |
Patients: 11% gastroesophageal junction, 89% gastric origin. 90% metastatic. 6% with ECOG PS of 2.
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 20 mg/m2 IV once on day 1
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2 IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m2)
14-day cycles
References
- Cascinu S, Galizia E, Labianca R, Ferraù F, Pucci F, Silva RR, Luppi G, Beretta GD, Berardi R, Scartozzi M. Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II trial. Cancer Chemother Pharmacol. 2011 Jul;68(1):37-43. Epub 2010 Sep 7. link to original article contains verified protocol PubMed
MCF
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MCF: Mitomycin, Cisplatin, Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ross et al. 2002 | 1995-1998 | Phase 3 (E-switch-ic) | ECF | Seems to have non-inferior OS |
Cascinu et al. 2010 | 2002-2005 | Randomized Phase II (C) | LdCF | Seems to have inferior OS |
Cascinu Patients: 11% gastroesophageal junction, 89% gastric origin. 90% metastatic. 6% with ECOG PS of 2.
Chemotherapy
- Mitomycin (Mutamycin) 7 mg/m2 (maximum dose of 14 mg) IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once per day on days 1 & 22
- Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 12,600 mg/m2)
Supportive medications
- Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis
42-day cycle for up to 5 cycles (6 months)
References
- Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. link to original article contains verified protocol PubMed
- Cascinu S, Galizia E, Labianca R, Ferraù F, Pucci F, Silva RR, Luppi G, Beretta GD, Berardi R, Scartozzi M. Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II trial. Cancer Chemother Pharmacol. 2011 Jul;68(1):37-43. Epub 2010 Sep 7. link to original article contains verified protocol PubMed
Paclitaxel monotherapy
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Regimen variant #1, weekly
Study | Evidence |
---|---|
Ilson et al. 2007 | Phase II |
Patients: 100% esophageal cancers. 66% adenocarcinoma, 34% squamous cell. Median ECOG PS 1, ranging 0-2.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22
Supportive medications
- Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
28-day cycles
Regimen variant #2, CI
Study | Evidence |
---|---|
Ajani et al. 1994 | Phase II |
Note: In contrast to the original reference, some guidelines list the dosage of paclitaxel as 135 to 175 mg/m2.
Patients: 100% esophageal cancer. 36% squamous cell, 64% adenocarcinoma histology.
Chemotherapy
- Paclitaxel (Taxol) 250 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Dosage adjusted based on toxicity down to 150 or 200 mg/m2, or up to 280 mg/m2
Supportive medications
- Dexamethasone (Decadron) 20 mg PO for 2 doses on day 1; 14 hours and 7 hours prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once on day 1; 60 minutes prior to Paclitaxel (Taxol)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 24 hours after the Paclitaxel (Taxol) infusion finishes
21-day cycles
References
- Ajani JA, Ilson DH, Daugherty K, Pazdur R, Lynch PM, Kelsen DP. Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst. 1994 Jul 20;86(14):1086-91. link to original article contains verified protocol PubMed
- Ilson DH, Wadleigh RG, Leichman LP, Kelsen DP. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol. 2007 May;18(5):898-902. Epub 2007 Mar 9. link to original article contains verified protocol PubMed
Metastatic or locally advanced disease, subsequent lines of therapy
CAPIRI
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CapeIRI: Capecitabine and IRInotecan
CAPIRI: CAPecitabine and IRInotecan
XELIRI: XELox (Capecitabine) and IRInotecan
XI: Xeloda (Capecitabine) and Irinotecan
Regimen
Study | Evidence |
---|---|
Leary et al. 2008 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Irinotecan (Camptosar) 250 mg/m2 IV over 30 to 90 minutes once on day 1
Supportive medications
- Atropine (Atropen) 0.25 mg SC once on day 1, given before Irinotecan (Camptosar)
- Loperamide (Imodium) 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool
- Ciprofloxacin (Cipro) 250 mg PO twice per day prn diarrhea lasting longer than 24 hours despite loperamide
21-day cycle for up to 8 cycles
References
- Leary A, Assersohn L, Cunningham D, Norman AR, Chong G, Brown G, Ross PJ, Costello C, Higgins L, Oates J. A phase II trial evaluating capecitabine and irinotecan as second line treatment in patients with oesophago-gastric cancer who have progressed on, or within 3 months of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2009 Aug;64(3):455-62. Epub 2008 Dec 23. link to original article contains verified protocol PubMed
Docetaxel monotherapy
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Regimen variant #1, 75 mg/m2, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kojima et al. 2020 (KEYNOTE-181) | 2015-2017 | Phase 3 (C) | Pembrolizumab | Inferior OS1 |
1Reported efficacy in KEYNOTE-181 is for patients with squamous cell carcinoma or with PD-L1 combined positive score of at least 10; in all patients the control arm might have inferior OS.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycles
Regimen variant #2, 100 mg/m2
Study | Evidence |
---|---|
Albertsson et al. 2007 | Phase II |
Patients: squamous cell or adenocarcinoma histology of the esophagus or gastric cardia.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycles
References
- Albertsson M, Johansson B, Friesland S, Kadar L, Letocha H, Frykholm G, Wagenius G. Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer. Med Oncol. 2007;24(4):407-12. link to original article contains protocol PubMed
- KEYNOTE-181: Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. Epub 2020 Oct 7. link to original article contains verified protocol PubMed NCT02564263
Docetaxel & Irinotecan
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Regimen
Study | Evidence |
---|---|
Burtness et al. 2009 | Phase II, <20 pts in this subgroup |
Patients: 79% adenocarcinoma, 21% squamous cell histology. All patients ECOG PS of 0 or 1, and unresectable/metastatic disease.
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV over 60 minutes once per day on days 1 & 8, given first
- Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
Supportive medications
- Dexamethasone (Decadron) as follows:
- 8 mg PO once per day on days 1 & 8; 12 hours before Docetaxel (Taxotere)
- 10 mg IV once per day on days 1 & 8, within 1 hour of chemotherapy
- 8 mg PO once per day on days 1 & 8; 12 hour afters chemotherapy
- Serotonin 5-HT3 antagonist IV once per day on days 1 & 8, within 1 hour before chemotherapy
- "Oral antiemetic therapy prescribed"
- Loperamide (Imodium) as needed
21-day cycles
References
- Burtness B, Gibson M, Egleston B, Mehra R, Thomas L, Sipples R, Quintanilla M, Lacy J, Watkins S, Murren JR, Forastiere AA. Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer. Ann Oncol. 2009 Jul;20(7):1242-8. Epub 2009 May 8. link to original article contains verified protocol link to PMC article PubMed
Erlotinib monotherapy
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Regimen
Study | Evidence |
---|---|
Ilson et al. 2010 | Phase II |
Patients: 57% adenocarcinoma, 43% squamous cell histology. 6% proximal esophagus, 35% distal esophagus, 59% gastroesophageal junction.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day, at least 1 hour before a meal, or 2 hours after a meal
28-day cycles
References
- Ilson DH, Kelsen D, Shah M, Schwartz G, Levine DA, Boyd J, Capanu M, Miron B, Klimstra D. A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. Cancer. 2011 Apr 1;117(7):1409-14. Epub 2010 Nov 8. link to original article contains verified protocol link to PMC article PubMed
Irinotecan monotherapy
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Regimen variant #1, 14-day cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kojima et al. 2020 (KEYNOTE-181) | 2015-2017 | Phase 3 (C) | Pembrolizumab | Inferior OS1 |
1Reported efficacy in KEYNOTE-181 is for patients with squamous cell carcinoma or with PD-L1 combined positive score of at least 10; in all patients the control arm might have inferior OS.
Chemotherapy
- Irinotecan (Camptosar) 180 mg/m2 IV once on day 1
14-day cycles
Regimen variant #2, 4 out of 6 weeks
Study | Evidence |
---|---|
Mühr-Wilkenshoff et al. 2003 | Phase II, <20 patients |
Note: In contrast to the primary reference, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles.
Patients: Ten with esophageal squamous cell carcinoma, three with esophageal adenocarcinoma
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22
42-day cycles
References
- Mühr-Wilkenshoff F, Hinkelbein W, Ohnesorge I, Wolf KJ, Riecken EO, Zeitz M, Scherübl H. A pilot study of irinotecan (CPT-11) as single-agent therapy in patients with locally advanced or metastatic esophageal carcinoma. Int J Colorectal Dis. 2003 Jul;18(4):330-4. Epub 2003 Feb 1. link to original article PubMed
- KEYNOTE-181: Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. Epub 2020 Oct 7. link to original article contains verified protocol PubMed NCT02564263
Irinotecan & Mitomycin
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Regimen
Study | Evidence |
---|---|
Bamias et al. 2003a | Phase II |
Patients: Advanced gastric and colorectal cancers. All previously received 5-fluorouracil-based chemotherapy.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV once on day 1
- Mitomycin (Mutamycin) 5 mg/m2 IV once on day 1
14-day cycles
References
- Bamias A, Papamichael D, Syrigos K, Pavlidis N. Phase II study of irinotecan and mitomycin C in 5-fluorouracil-pretreated patients with advanced colorectal and gastric cancer. J Chemother. 2003 Jun;15(3):275-81. link to original article contains protocol PubMed
IRIS
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IRIS: IRInotecan & S-1
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Huang et al. 2019 (ESWN 01) | 2014-2016 | Phase 3 (E-switch-ic) | S-1 | Superior PFS |
Chemotherapy
- Irinotecan (Camptosar) 160 mg/m2 IV once on day 1, given first
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO twice per day on days 1 to 10
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 10
- BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 10
14-day cycles
References
- ESWN 01: Huang J, Xu B, Liu Y, Huang J, Lu P, Ba Y, Wu L, Bai Y, Zhang S, Feng J, Cheng Y, Li J, Wen L, Yuan X, Ma C, Hu C, Fan Q, Wang X. Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial. Cancer Commun (Lond). 2019 Apr 2;39(1):16. link to original article link to PMC article contains verified protocol PubMed NCT02319187
Paclitaxel monotherapy
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Regimen variant #1, weekly
Study | Evidence |
---|---|
Ilson et al. 2007 | Phase II |
Patients: 100% esophageal cancers. 66% adenocarcinoma, 34% squamous cell. Median ECOG PS 1, ranging 0-2.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22
Supportive medications
- Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
- Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Paclitaxel (Taxol)
28-day cycles
Regimen variant #2, 80 mg/m2, 3 out of 4 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kojima et al. 2020 (KEYNOTE-181) | 2015-2017 | Phase 3 (C) | Pembrolizumab | Inferior OS1 |
1Reported efficacy in KEYNOTE-181 is for patients with squamous cell carcinoma or with PD-L1 combined positive score of at least 10; in all patients the control arm might have inferior OS.
This is the lower bound of dosing specified in KEYNOTE-181.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #3, 100 mg/m2, 3 out of 4 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kojima et al. 2020 (KEYNOTE-181) | 2015-2017 | Phase 3 (C) | Pembrolizumab | Inferior OS1 |
1Reported efficacy in KEYNOTE-181 is for patients with squamous cell carcinoma or with PD-L1 combined positive score of at least 10; in all patients the control arm might have inferior OS.
This is the upper bound of dosing specified in the protocol.
Chemotherapy
- Paclitaxel (Taxol) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Ilson DH, Wadleigh RG, Leichman LP, Kelsen DP. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol. 2007 May;18(5):898-902. Epub 2007 Mar 9. link to original article contains verified protocol PubMed
- KEYNOTE-181: Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. Epub 2020 Oct 7. link to original article contains verified protocol PubMed NCT02564263
S-1 monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Huang et al. 2019 (ESWN 01) | 2014-2016 | Phase 3 (C) | IRIS | Inferior PFS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO twice per day on days 1 to 14
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 14
- BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 14
21-day cycles
References
- ESWN 01: Huang J, Xu B, Liu Y, Huang J, Lu P, Ba Y, Wu L, Bai Y, Zhang S, Feng J, Cheng Y, Li J, Wen L, Yuan X, Ma C, Hu C, Fan Q, Wang X. Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial. Cancer Commun (Lond). 2019 Apr 2;39(1):16. link to original article link to PMC article contains verified protocol PubMed NCT02319187