Difference between revisions of "Classical Hodgkin lymphoma - null regimens"

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the [[Hodgkin_lymphoma|main Hodgkin lymphoma page]] for current regimens.
+
The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the [[Mantle cell lymphoma|main mantle cell lymphoma page]] for current regimens.
  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
  
−
=Consolidation after upfront therapy=
+
=Adjuvant therapy=
−
 
 
 
==Observation==
 
==Observation==
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
Line 12: Line 11:
 
===Regimen===
 
===Regimen===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|rowspan=2|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(73)91672-3/fulltext Young et al. 1973]
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90057-4/fulltext Lacour et al. 1980]
−
|rowspan=2 style="background-color:#1a9851" |Phase III (C)
+
|1972-1979
−
|Intermittent BCNU
+
|style="background-color:#1a9851"|Phase III (C)
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+
|Polya.Polyu
 +
| style="background-color:#fee08b" |Might have inferior OS
 
|-
 
|-
−
|Intermittent MOPP
+
|[https://www.nejm.org/doi/full/10.1056/NEJM197602192940801 Bonadonna et al. 1976]
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+
|1973-1975
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer#CMF|CMF]]
 +
|style="background-color:#d73027"|Inferior RFS
 
|-
 
|-
−
|[https://www.nejm.org/doi/10.1056/NEJMoa022628 Aleman et al. 2003 (EORTC 20884)]
+
|[http://www.tandfonline.com/doi/full/10.1080/0284186X.2017.1400179 Jensen et al. 2017 (CBC 02)]
 +
|1975-1978
 
| style="background-color:#1a9851" |Phase III (C)
 
| style="background-color:#1a9851" |Phase III (C)
−
|[[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]]
+
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2 y
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS36
+
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/104/12/3483.long Straus et al. 2004]
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91385-5/fulltext Rubens et al. 1983]
 +
|1975-1979
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer_-_historical#Melphalan_monotherapy|Melphalan]]
 +
| style="background-color:#fee08b" |Might have inferior RFS
 +
|-
 +
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91683-5/abstract Baum et al. 1983 (NATO)]
 +
|1977-1981
 
| style="background-color:#1a9851" |Phase III (C)
 
| style="background-color:#1a9851" |Phase III (C)
−
|[[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]]
+
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2 y
−
| style="background-color:#fee08b" |Might have inferior OS
+
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|rowspan=3|[https://link.springer.com/article/10.1007/BF01806239 Brinker et al. 1983 (DBCG 77B)]
 +
|rowspan=3|1977-1983
 +
|rowspan=3 style="background-color:#1a9851" |Phase III (C)
 +
|1. [[Breast_cancer#CMF|CMF]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
 +
|-
 +
|2. [[Breast_cancer_-_historical#Cyclophosphamide_monotherapy|Cyclophosphamide]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS (*)
 +
|-
 +
|3. [[Breast_cancer_-_historical#Levamisole_monotherapy|Levamisole]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of IDFS/OS
 +
|-
 +
|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
 +
|rowspan=2|1978-1981
 +
|rowspan = 2 style="background-color:#1a9851" |Phase III (C)
 +
|1. [[Breast_cancer_-_historical#CMFPT|CMFPT]]
 +
| style="background-color:#d73027" |Inferior DFS
 +
|-
 +
|2. [[Breast_cancer_-_historical#PT|PT]]
 +
| style="background-color:#d73027" |Inferior DFS
 +
|-
 +
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS IV)]
 +
|1978-1981
 +
|style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer_-_historical#PT|PT]]
 +
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
|-
 
|-
−
|[http://jco.ascopubs.org/content/29/32/4234.long Borchmann et al. 2011 (GHSG HD12)]
+
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(87)90762-8/fulltext Stewart et al. 1987 (Scottish Tamoxifen Trial)]
 +
|1978-1984
 
| style="background-color:#1a9851" |Phase III (C)
 
| style="background-color:#1a9851" |Phase III (C)
−
|[[Complex_multipart_regimens#GHSG_HD12|See link]]
+
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5 y
−
|style="background-color:#fee08b"|[[Complex_multipart_regimens#GHSG_HD12|See link]]
+
| style="background-color:#d73027" |Inferior OS (*)
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1408648 Radford et al. 2015 (UK NCRI RAPID)]
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 Fisher et al. 1989 (NSABP B-13)]
 +
|1981-1988
 
| style="background-color:#1a9851" |Phase III (C)
 
| style="background-color:#1a9851" |Phase III (C)
−
|[[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]]
+
|[[Breast_cancer_-_historical#MF|MF]]; sequential
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS36
+
| style="background-color:#d73027" |Inferior DFS (*)
 
|-
 
|-
−
|rowspan=2|[https://www.redjournal.org/article/S0360-3016(17)33984-6/fulltext Thomas et al. 2017 (EORTC-GELA H9-F)]
+
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 Mansour et al. 1989 (INT-0011)]
−
|rowspan=2 style="background-color:#1a9851" |Phase III (E-de-esc)
+
|1981-1988
−
|[[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]] x 20 Gy
+
| style="background-color:#1a9851" |Phase III (C)
−
| style="background-color:#d3d3d3" |Not reported
+
|[[Breast_cancer_-_historical#CMFP|CMFP]]
 +
|style="background-color:#d73027"|Inferior DFS
 
|-
 
|-
−
|[[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]] x 36 Gy
+
|[https://www.ejcancer.com/article/S0959-8049(04)00565-9/fulltext Rydén et al. 2005 (SBII:2pre)]
 +
|1986-1991
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 2 y
 
| style="background-color:#d73027" |Inferior RFS
 
| style="background-color:#d73027" |Inferior RFS
 +
|-
 +
|[http://jco.ascopubs.org/content/23/33/8313.long Hutchins et al. 2005 (INT-0102)]
 +
|1989-1993
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5 y
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 +
|-
 +
|[https://ascopubs.org/doi/full/10.1200/JCO.2001.19.19.3929 Paradiso et al. 2001]
 +
|1989-1994
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer#FEC_2|FEC]]
 +
| style="background-color:#fc8d59" |Seems to have inferior DFS
 +
|-
 +
|[https://ascopubs.org/doi/full/10.1200/JCO.2005.03.0783 Colleoni et al. 2006 (IBCSG 13-93)]
 +
|1993-1999
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5 y
 +
| style="background-color:#1a9850" |Superior DFS
 +
|-
 +
|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
 +
|1994-1999
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; q3wk
 +
|style="background-color:#d73027"|Inferior OS
 +
|-
 +
|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
 +
|1995-1998
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]; q3wk
 +
|style="background-color:#d73027"|Inferior DFS
 +
|-
 +
|[https://academic.oup.com/annonc/article/27/5/806/2769820 Zdenkowski et al. 2016 (ANZ0501 LATER)]
 +
|2007-2012
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_2|Letrozole]] x 5 y
 +
| style="background-color:#fee08b" |Might have inferior DFS
 
|-
 
|-
 
|}
 
|}
−
''No further treatment.''
+
''Note: No further systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Reported efficacy for NSABP B-13 is based on the 1996 update. Reported efficacy for the Scottish Tamoxifen Trial is based on the 2001 update. Reported efficacy for DBCG 77B is based on the 2010 update.''
 
====Preceding treatment====
 
====Preceding treatment====
−
*Young et al. 1973: [[Hodgkin_lymphoma#MOPP|MOPP]]
+
*Bonadonna et al. 1976: [[Surgery#Mastectomy|Mastectomy]]
−
*EORTC 20884: [[Hodgkin_lymphoma#MOPP-ABV_3|MOPP-ABV]] x 6 to 8
+
*ECOG E1180: [[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
−
*Straus et al. 2004: [[Hodgkin_lymphoma#ABVD_2|ABVD]] x 6
+
*INT 0148/CALGB 9344: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
−
*GHSG HD12: [[Hodgkin_lymphoma#eBEACOPP_2|Escalated BEACOPP]] x 8 versus [[Hodgkin_lymphoma#eBEACOPP_2|Escalated BEACOPP]] x 4, then [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]] x 4
+
*NSABP B-28: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
−
*UK NCRI RAPID: [[Hodgkin_lymphoma#ABVD|ABVD]] x 3
+
*INT-0102: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FAC_2|CAF]] x 6 versus [[Breast_cancer#CMF|CMF]] x 6
−
*EORTC-GELA H9-F: [[Hodgkin_lymphoma#EBVP|EBVP]] x 6
+
*IBCSG 13-93: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 or [[Breast_cancer#EC_2|EC]] x 4, then [[Breast_cancer#CMF|CMF]] x 3
 +
*ANZ0501 LATER: At least 4 years of any endocrine therapy
 
===References===
 
===References===
−
# Young RC, Canellos GP, Chabner BA, Schein PS, DeVita VT. Maintenance chemotherapy for advanced Hodgkin's disease in remission. Lancet. 1973 Jun 16;1(7816):1339-43. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(73)91672-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/4122739 PubMed]
+
# Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. [https://www.nejm.org/doi/full/10.1056/NEJM197602192940801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1246307 PubMed]
−
# '''EORTC 20884:''' Aleman BM, Raemaekers JM, Tirelli U, Bortolus R, van 't Veer MB, Lybeert ML, Keuning JJ, Carde P, Girinsky T, van der Maazen RW, Tomsic R, Vovk M, van Hoof A, Demeestere G, Lugtenburg PJ, Thomas J, Schroyens W, De Boeck K, Baars JW, Kluin-Nelemans JC, Carrie C, Aoudjhane M, Bron D, Eghbali H, Smit WG, Meerwaldt JH, Hagenbeek A, Pinna A, Henry-Amar M; European Organization for Research and Treatment of Cancer Lymphoma Group. Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med. 2003 Jun 12;348(24):2396-406. [https://www.nejm.org/doi/10.1056/NEJMoa022628 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12802025 PubMed]
+
## '''Update:''' Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2904::AID-CNCR2820390677%3E3.0.CO;2-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/326384 PubMed]
−
# Straus DJ, Portlock CS, Qin J, Myers J, Zelenetz AD, Moskowitz C, Noy A, Goy A, Yahalom J. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood. 2004 Dec 1;104(12):3483-9. Epub 2004 Aug 17. [http://www.bloodjournal.org/content/104/12/3483.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15315964 PubMed]
+
## '''Update:''' Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. [https://www.ncbi.nlm.nih.gov/pubmed/3839424 PubMed]
−
# '''GHSG HD12:''' Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage Hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. [http://jco.ascopubs.org/content/29/32/4234.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21990399 PubMed]
+
## '''Update:''' Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. [https://www.nejm.org/doi/ref/10.1056/NEJM199504063321401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7877646 PubMed]
−
## '''Update:''' von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30140-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30290903 PubMed]
+
# Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J. Adjuvant treatment with polyadenylic-polyuridylic acid (Polya-Polyu) in operable breast cancer. Lancet. 1980 Jul 26;2(8187):161-4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90057-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6105336 PubMed]
−
<!-- # '''Abstract:''' Radford, John, Barrington, Sally, Counsell, Nicholas, Pettengell, Ruth, Johnson, Peter, Wimperis, Jennie, Coltart, Stewart, Culligan, Dominic, Lister, Andrew, Bessell, Eric, Kruger, Anton, Popova, Bilyana, Hancock, Barry, Hoskin, Peter, Illidge, Timothy, O'Doherty, Michael. Involved Field Radiotherapy Versus No Further Treatment in Patients with Clinical Stages IA and IIA Hodgkin Lymphoma and a 'Negative' PET Scan After 3 Cycles ABVD. Results of the UK NCRI RAPID Trial. ASH Annual Meeting Abstracts 2012 120: 547 [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/547 link to original abstract] -->
+
# '''NATO:''' Baum M, Brinkley DM, Dosset JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Lea JC, Richards D, Ellis SH. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer: interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet. 1983 Feb 5;1(8319):257-61. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91683-5/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6130291 PubMed]
−
# '''UK NCRI RAPID:''' Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. [https://www.nejm.org/doi/full/10.1056/NEJMoa1408648 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25901426 PubMed]
+
## '''Update:''' Baum M, Brinkley DM, Dosset JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Richards D, Ellis SH. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer: analysis at six years by Nolvadex Adjuvant Trial Organisation. Lancet. 1985 Apr 13;1(8433):836-40. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(85)92206-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2858709 PubMed]
−
# '''EORTC-GELA H9-F:''' Thomas J, Fermé C, Noordijk EM, Morschhauser F, Girinsky T, Gaillard I, Lugtenburg PJ, André M, Lybeert MLM, Stamatoullas A, Beijert M, Hélias P, Eghbali H, Gabarre J, van der Maazen RWM, Jaubert J, Bouabdallah K, Boulat O, Roesink JM, Christian B, Ong F, Bordessoule D, Tertian G, Gonzalez H, Vranovsky A, Quittet P, Tirelli U, de Jong D, Audouin J, Aleman BMP, Henry-Amar M. Comparison of 36 Gy, 20 Gy, or no radiation therapy after 6 cycles of EBVP chemotherapy and complete remission in early-stage Hodgkin lymphoma without risk factors: results of the EORTC-GELA H9-F intergroup randomized trial. Int J Radiat Oncol Biol Phys. 2018 Apr 1;100(5):1133-1145. Epub 2017 Oct 27. [https://www.redjournal.org/article/S0360-3016(17)33984-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29229324 PubMed]
+
# Rubens RD, Hayward JL, Knight RK, Bulbrook RD, Fentiman IS, Chaudary M, Howell A, Bush H, Crowther D, Sellwood RA, George WD, Howat JM. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet. 1983 Apr 16;1(8329):839-43. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91385-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6132179 PubMed]
 +
# '''DBCG 77B:''' Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. [https://link.springer.com/article/10.1007/BF01806239 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6347278 PubMed]
 +
## '''Update:''' Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24969/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20186830 PubMed]
 +
# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
 +
# '''Scottish Tamoxifen Trial:''' Stewart HJ, Taylor W, Forrest P. Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial: report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh. Lancet. 1987 Jul 25;2(8552):171-5. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(87)90762-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2885637 PubMed]
 +
## '''Update:''' Stewart HJ, Forrest AP, Everington D, McDonald CC, Dewar JA, Hawkins RA, Prescott RJ, George WD; The Scottish Cancer Trials Breast Group. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. Br J Cancer. 1996 Jul;74(2):297-9. [https://www.nature.com/articles/bjc1996356 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2074573/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/8688340 PubMed]
 +
## '''Update:''' Stewart HJ, Prescott RJ, Forrest AP. Scottish adjuvant tamoxifen trial: a randomized study updated to 15 years. J Natl Cancer Inst. 2001 Mar 21;93(6):456-62. [https://academic.oup.com/jnci/article/93/6/456/2906503 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11259471 PubMed]
 +
# '''NSABP B-13:''' Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644531 PubMed]
 +
## '''Update:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
 +
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
 +
# '''INT-0011:''' Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2915651 PubMed]
 +
# '''LCBS V:''' Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644533 PubMed]
 +
# Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.19.3929 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11579113 PubMed]
 +
# '''INT 0148/CALGB 9344:''' Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. [http://jco.ascopubs.org/content/21/6/976.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12637460 PubMed]
 +
# '''SBII:2pre:''' Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. [https://www.ejcancer.com/article/S0959-8049(04)00565-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15661551 PubMed]
 +
## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. [http://jco.ascopubs.org/content/34/19/2232.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27161974 PubMed]
 +
<!-- Presented in abstract form at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003; interim results were presented at the 2000 NIH Consensus Development Conference, Bethesda, MD, November 1-3, 2000. -->
 +
# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [http://jco.ascopubs.org/content/23/16/3686.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15897552 PubMed]
 +
# '''INT-0102:''' Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of intergroup protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed]
 +
# '''IBCSG 13-93:''' Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. [https://ascopubs.org/doi/full/10.1200/JCO.2005.03.0783 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16505417 PubMed]
 +
# '''ANZ0501 LATER:''' Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. [https://academic.oup.com/annonc/article/27/5/806/2769820 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26861603 PubMed]
 +
# '''CBC 02:''' Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen Breast Cancer Trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. [http://www.tandfonline.com/doi/full/10.1080/0284186X.2017.1400179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29165021 PubMed]
  
−
=Maintenance after upfront therapy=
+
==Placebo==
−
==Observation==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
Line 80: Line 182:
 
===Regimen===
 
===Regimen===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
−
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 Fisher et al. 1975 (NSABP B-05)]
 +
|1972-1975
 +
|style="background-color:#1a9851"|Phase III (C)
 +
|[[Breast_cancer_-_historical#Melphalan_monotherapy|Melphalan]]
 +
|style="background-color:#fee08b" |Might have inferior DFS (*)
 +
|-
 +
|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200802 Fisher et al. 1989 (NSABP B-14)]
 +
|1982-1987
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
 +
| style="background-color:#d73027" |Inferior OS (*)
 +
|-
 +
|[http://jco.ascopubs.org/content/19/4/931.full Fisher et al. 2001 (NSABP B-23)]
 +
|1991-1998
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.nejm.org/doi/full/10.1056/NEJMoa032312 Goss et al. 2003 (NCIC CTG MA.17)]
 +
|1998-2002
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_2|Letrozole]]
 +
| style="background-color:#d73027" |Inferior DFS
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJM197412052912305 Sokal et al. 1974]
+
|[http://jco.ascopubs.org/content/26/12/1965.long Mamounas et al. 2008 (NSABP B-33)]
−
|style="background-color:#91cf61"|Randomized, <20 pts in this subgroup (C)
+
|2001-2003
−
|[[Hodgkin_lymphoma_-_historical#Bacillus_Calmette-Gu.C3.A9rin_.28BCG.29_monotherapy|BCG]]
+
| style="background-color:#1a9851" |Phase III (C)
−
| style="background-color:#d73027" |Inferior PFS
+
|[[Breast_cancer,_ER-positive#Exemestane_monotherapy|Exemestane]]
 +
| style="background-color:#d73027" |Inferior RFS
 
|-
 
|-
 
|}
 
|}
−
''Note: this study was open to patients with "malignant lymphoma" but the majority had Hodgkin disease.''
+
''No active antineoplastic treatment. Used as a comparator arm, historically. Reported efficacy for NSABP B-05 is based on the 1986 update. Reported efficacy for NSABP B-14 based on the 2004 update.''
−
====Immunotherapy====
+
====Preceding treatment====
−
*[[Bacillus Calmette-Guérin (BCG)]]
+
*NSABP B-05: [[Surgery#Mastectomy|Mastectomy]]
 +
*NSABP B-14: [[Surgery#Breast_cancer_surgery|Surgery]]
 +
*NSABP B-23: [[Breast_cancer#CMF|CMF]] x 6 versus [[Breast_cancer#AC_2|AC]] x 4
 +
*NCIC CTG MA.17: [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 +
*NSABP B-33: [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]] x 5y
 +
 
 
===References===
 
===References===
−
# Sokal JE, Aungst CW, Snyderman M. Delay in progression of malignant lymphoma after BCG vaccination. N Engl J Med. 1974 Dec 5;291(23):1226-30. [https://www.nejm.org/doi/full/10.1056/NEJM197412052912305 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/4609380 PubMed]
+
# '''NSABP B-05:''' Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. [https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1105174 PubMed]
 +
## '''Update:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2883::AID-CNCR2820390676%3E3.0.CO;2-9/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
 +
## '''Update:''' Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. [https://ascopubs.org/doi/full/10.1200/JCO.1986.4.6.929 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3519883 PubMed]
 +
# '''NSABP B-14:''' Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, Dimitrov NV, Wolmark N, Wickerham DL, Fisher ER, Margolese R, Robidoux A, Shibata H, Terz J, Peterson AHG, Feldman MI, Farrar W, Evans J, Lickley HL, Ketner M. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989 Feb 23;320(8):479-84. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200802 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2644532 PubMed]
 +
## '''Update:''' Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J, Redmond C, Fisher ER, Bowman DM, Deschênes L, Dimitrov NV, Margolese RG, Robidoux A, Shibata H, Terz J, Paterson AH, Feldman MI, Farrar W, Evans J, Lickley HL. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst. 1996 Nov 6;88(21):1529-42. [https://academic.oup.com/jnci/article/88/21/1529/922662 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8901851 PubMed]
 +
## '''Update:''' Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 2001 May 2;93(9):684-90. [https://academic.oup.com/jnci/article/93/9/684/2906559 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11333290 PubMed]
 +
## '''Update:''' Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, Wolmark N; National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004 Sep 4-10;364(9437):858-68. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(04)16981-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15351193 PubMed]
 +
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
 +
# '''NSABP B-23:''' Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed]
 +
## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
 +
# '''NCIC CTG MA.17:''' Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. [https://www.nejm.org/doi/full/10.1056/NEJMoa032312 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14551341 PubMed]
 +
## '''Update:''' Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. [http://jnci.oxfordjournals.org/content/97/17/1262.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16145047 PubMed]
 +
## '''QoL analysis:''' Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005 Oct 1;23(28):6931-40. Epub 2005 Sep 12. [https://ascopubs.org/doi/full/10.1200/JCO.2005.11.181 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16157934 PubMed]
 +
## '''Update:''' Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1956.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332474 PubMed]
 +
## '''Subgroup analysis:''' Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1948.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332475 PubMed]
 +
## '''Update:''' Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. [http://jco.ascopubs.org/content/30/7/718.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295549/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22042967 PubMed]
 +
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). -->
 +
# '''NSABP B-33:''' Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1965.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332472 PubMed]
  
−
=Maintenance after salvage therapy=
+
=Metastatic disease, maintenance after first-line therapy=
−
 
+
==Observation==
−
==Placebo==
 
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|-
 
|[[#top|back to top]]
 
|[[#top|back to top]]
 
|}
 
|}
−
 
 
===Regimen===
 
===Regimen===
 
{| class="wikitable" style="width: 100%; text-align:center;"  
 
{| class="wikitable" style="width: 100%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 25%"|Comparator
−
!style="width: 20%"|Comparator
+
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
|-
 +
|[https://ascopubs.org/doi/abs/10.1200/JCO.1998.16.5.1669 Falkson et al. 1998 (INT-0077)]
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|CMF(P)TH
 +
| style="background-color:#d73027" |Inferior RFS
 +
|-
 +
|[https://ascopubs.org/doi/full/10.1200/JCO.2004.08.054 Sparano et al. 2004 (ECOG E2196)]
 +
| style="background-color:#1a9851" |Phase III (C)
 +
|Marimastat
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60165-9/fulltext Moskowitz et al. 2015 (AETHERA)]
+
|[https://link.springer.com/article/10.1007%2Fs10549-010-0860-9 Alba et al. 2010 (GEICAM 2001-01)]
−
|2010-2012
 
 
| style="background-color:#1a9851" |Phase III (C)
 
| style="background-color:#1a9851" |Phase III (C)
−
|[[Hodgkin_lymphoma#Brentuximab_vedotin_monotherapy_3|Brentuximab vedotin]]
+
|PLD x 6
−
| style="background-color:#d73027" |Inferior PFS
+
| style="background-color:#d73027" |Inferior TTP
 
|-
 
|-
−
|[https://www.tandfonline.com/doi/full/10.1080/10428194.2016.1182164 von Treskckow et al. 2016 (PATH)]
+
|[https://ascopubs.org/doi/full/10.1200/JCO.2012.45.2490 Park et al. 2013 (KCSG-BR07-02)]
−
|{{#subobject:xx|ToDo=1}}
 
 
| style="background-color:#1a9851" |Phase III (C)
 
| style="background-color:#1a9851" |Phase III (C)
−
|Panobinostat
+
|[[Breast_cancer#Gemcitabine_.26_Paclitaxel|PG]]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS (*)
+
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
−
''No further active antineoplastic treatment after transplant. Note that PATH had a very low accrual and was not powered to investigate the original primary endpoint (DFS).''
+
''No further treatment.''
 
====Preceding treatment====
 
====Preceding treatment====
−
*Autologous HSCT (preparative regimen not specified)
+
*ECOG E2196: Doxorubicin- and/or taxane-containing chemotherapy x 6-8
 +
*GEICAM 2001-01: A x 3, then D x 3
 +
*KCSG-BR07-02: [[Breast_cancer#Gemcitabine_.26_Paclitaxel|PG]] x 6
  
 
===References===
 
===References===
−
# '''AETHERA:''' Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60165-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25796459 PubMed]
+
# '''INT-0077:''' Falkson G, Gelman RS, Pandya KJ, Osborne CK, Tormey D, Cummings FJ, Sledge GW, Abeloff MD. Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment. J Clin Oncol. 1998 May;16(5):1669-76. [https://ascopubs.org/doi/abs/10.1200/JCO.1998.16.5.1669 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9586877 PubMed]
−
## '''HRQoL analysis:''' Ramsey SD, Nademanee A, Masszi T, Holowiecki J, Abidi M, Chen A, Stiff P, Viviani S, Sweetenham JW, Radford J, Zhu Y, Bonthapally V, Thomas E, Richhariya A, Hunder NN, Walewski J, Moskowitz CH. Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma. Br J Haematol. 2016 Dec;175(5):860-867. Epub 2016 Sep 21. [https://onlinelibrary.wiley.com/doi/abs/10.1111/bjh.14316 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5621593/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27649689 PubMed]
+
# '''ECOG E2196:''' Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. [https://ascopubs.org/doi/full/10.1200/JCO.2004.08.054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15570070 PubMed]
−
## '''Update:''' Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Viviani S, Bachanova V, Sureda A, McClendon T, Lee C, Lisano J, Sweetenham J. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018 Dec 20;132(25):2639-2642. Epub 2018 Sep 28. [http://www.bloodjournal.org/content/132/25/2639.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30266774 PubMed]
+
# '''GEICAM 2001-01:''' Alba E, Ruiz-Borrego M, Margelí M, Rodríguez-Lescure A, Sánchez-Rovira P, Ruiz A, Mel-Lorenzo JR, Ramos-Vázquez M, Ribelles N, Calvo E, Casado A, Márquez A, Vicente D, García-Sáenz JA, Martín M. Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. Breast Cancer Res Treat. 2010 Jul;122(1):169-76. Epub 2010 Apr 2. [https://link.springer.com/article/10.1007%2Fs10549-010-0860-9 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20361253 PubMed]
−
# '''PATH:''' von Tresckow B, Morschhauser F, Szer J, Eichenauer DA, Abramson JS, Sureda A, Engert A. Panobinostat consolidation in patients with Hodgkin lymphoma at risk for relapse after high dose chemotherapy and autologous stem cell transplant: final results after early trial discontinuation. Leuk Lymphoma. 2017 Jan;58(1):222-225. Epub 2016 May 17. [https://www.tandfonline.com/doi/full/10.1080/10428194.2016.1182164 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27184350 PubMed]
+
# '''KCSG-BR07-02:''' Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. [https://ascopubs.org/doi/full/10.1200/JCO.2012.45.2490 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23569309 PubMed]
  
−
[[Category:Hodgkin lymphoma regimens]]
+
[[Category:Breast cancer regimens]]
 
[[Category:Null regimens]]
 
[[Category:Null regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Aggressive lymphomas]]
+
[[Category:Malignant breast neoplasm]]

Revision as of 03:10, 4 February 2020

The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the main mantle cell lymphoma page for current regimens.


Adjuvant therapy

Observation

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Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lacour et al. 1980 1972-1979 Phase III (C) Polya.Polyu Might have inferior OS
Bonadonna et al. 1976 1973-1975 Phase III (C) CMF Inferior RFS
Jensen et al. 2017 (CBC 02) 1975-1978 Phase III (C) Tamoxifen x 2 y Seems to have inferior OS
Rubens et al. 1983 1975-1979 Phase III (C) Melphalan Might have inferior RFS
Baum et al. 1983 (NATO) 1977-1981 Phase III (C) Tamoxifen x 2 y Inferior OS
Brinker et al. 1983 (DBCG 77B) 1977-1983 Phase III (C) 1. CMF Seems to have inferior OS (*)
2. Cyclophosphamide Seems to have inferior OS (*)
3. Levamisole Did not meet primary endpoints of IDFS/OS
Goldhirsch et al. 1984 (LBCS III) 1978-1981 Phase III (C) 1. CMFPT Inferior DFS
2. PT Inferior DFS
Goldhirsch et al. 1984 (LBCS IV) 1978-1981 Phase III (C) PT Seems to have inferior DFS
Stewart et al. 1987 (Scottish Tamoxifen Trial) 1978-1984 Phase III (C) Tamoxifen x 5 y Inferior OS (*)
Fisher et al. 1989 (NSABP B-13) 1981-1988 Phase III (C) MF; sequential Inferior DFS (*)
Mansour et al. 1989 (INT-0011) 1981-1988 Phase III (C) CMFP Inferior DFS
Rydén et al. 2005 (SBII:2pre) 1986-1991 Phase III (C) Tamoxifen x 2 y Inferior RFS
Hutchins et al. 2005 (INT-0102) 1989-1993 Phase III (C) Tamoxifen x 5 y Did not meet primary endpoint of DFS
Paradiso et al. 2001 1989-1994 Phase III (C) FEC Seems to have inferior DFS
Colleoni et al. 2006 (IBCSG 13-93) 1993-1999 Phase III (C) Tamoxifen x 5 y Superior DFS
Henderson et al. 2003 (INT 0148/CALGB 9344) 1994-1999 Phase III (C) Paclitaxel; q3wk Inferior OS
Mamounas et al. 2005 (NSABP B-28) 1995-1998 Phase III (C) Paclitaxel; q3wk Inferior DFS
Zdenkowski et al. 2016 (ANZ0501 LATER) 2007-2012 Phase III (C) Letrozole x 5 y Might have inferior DFS

Note: No further systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Reported efficacy for NSABP B-13 is based on the 1996 update. Reported efficacy for the Scottish Tamoxifen Trial is based on the 2001 update. Reported efficacy for DBCG 77B is based on the 2010 update.

Preceding treatment

References

  1. Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. link to original article PubMed
    1. Update: Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. link to original article PubMed
    2. Update: Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. PubMed
    3. Update: Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. link to original article PubMed
  2. Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J. Adjuvant treatment with polyadenylic-polyuridylic acid (Polya-Polyu) in operable breast cancer. Lancet. 1980 Jul 26;2(8187):161-4. link to original article PubMed
  3. NATO: Baum M, Brinkley DM, Dosset JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Lea JC, Richards D, Ellis SH. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer: interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet. 1983 Feb 5;1(8319):257-61. link to original article contains protocol PubMed
    1. Update: Baum M, Brinkley DM, Dosset JA, McPherson K, Patterson JS, Rubens RD, Smiddy FG, Stoll BA, Wilson A, Richards D, Ellis SH. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer: analysis at six years by Nolvadex Adjuvant Trial Organisation. Lancet. 1985 Apr 13;1(8433):836-40. link to original article PubMed
  4. Rubens RD, Hayward JL, Knight RK, Bulbrook RD, Fentiman IS, Chaudary M, Howell A, Bush H, Crowther D, Sellwood RA, George WD, Howat JM. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet. 1983 Apr 16;1(8329):839-43. link to original article PubMed
  5. DBCG 77B: Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. link to original article contains verified protocol PubMed
    1. Update: Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. link to original article PubMed
  6. LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article PubMed
  7. Scottish Tamoxifen Trial: Stewart HJ, Taylor W, Forrest P. Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial: report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh. Lancet. 1987 Jul 25;2(8552):171-5. link to original article PubMed
    1. Update: Stewart HJ, Forrest AP, Everington D, McDonald CC, Dewar JA, Hawkins RA, Prescott RJ, George WD; The Scottish Cancer Trials Breast Group. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. Br J Cancer. 1996 Jul;74(2):297-9. link to original article link to PMC article PubMed
    2. Update: Stewart HJ, Prescott RJ, Forrest AP. Scottish adjuvant tamoxifen trial: a randomized study updated to 15 years. J Natl Cancer Inst. 2001 Mar 21;93(6):456-62. link to original article PubMed
  8. NSABP B-13: Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. link to original article PubMed
    1. Update: Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. link to original article PubMed
    2. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed
  9. INT-0011: Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. link to original article PubMed
  10. LCBS V: Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. link to original article PubMed
  11. Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. link to original article contains verified protocol PubMed
  12. INT 0148/CALGB 9344: Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
  13. SBII:2pre: Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. link to original article PubMed
    1. Update: Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. link to original article PubMed
  14. NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed
  15. INT-0102: Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of intergroup protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. link to original article PubMed
  16. IBCSG 13-93: Colleoni M, Gelber S, Goldhirsch A, Aebi S, Castiglione-Gertsch M, Price KN, Coates AS, Gelber RD; International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13-93. J Clin Oncol. 2006 Mar 20;24(9):1332-41. Epub 2006 Feb 27. link to original article contains verified protocol PubMed
  17. ANZ0501 LATER: Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. link to original article PubMed
  18. CBC 02: Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen Breast Cancer Trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. link to original article PubMed

Placebo

back to top

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fisher et al. 1975 (NSABP B-05) 1972-1975 Phase III (C) Melphalan Might have inferior DFS (*)
Fisher et al. 1989 (NSABP B-14) 1982-1987 Phase III (C) Tamoxifen Inferior OS (*)
Fisher et al. 2001 (NSABP B-23) 1991-1998 Phase III (C) Tamoxifen Did not meet primary endpoint of OS
Goss et al. 2003 (NCIC CTG MA.17) 1998-2002 Phase III (C) Letrozole Inferior DFS
Mamounas et al. 2008 (NSABP B-33) 2001-2003 Phase III (C) Exemestane Inferior RFS

No active antineoplastic treatment. Used as a comparator arm, historically. Reported efficacy for NSABP B-05 is based on the 1986 update. Reported efficacy for NSABP B-14 based on the 2004 update.

Preceding treatment

References

  1. NSABP B-05: Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. link to original article PubMed
    1. Update: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article PubMed
    2. Update: Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. link to original article PubMed
  2. NSABP B-14: Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, Dimitrov NV, Wolmark N, Wickerham DL, Fisher ER, Margolese R, Robidoux A, Shibata H, Terz J, Peterson AHG, Feldman MI, Farrar W, Evans J, Lickley HL, Ketner M. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med. 1989 Feb 23;320(8):479-84. link to original article contains verified protocol PubMed
    1. Update: Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J, Redmond C, Fisher ER, Bowman DM, Deschênes L, Dimitrov NV, Margolese RG, Robidoux A, Shibata H, Terz J, Paterson AH, Feldman MI, Farrar W, Evans J, Lickley HL. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst. 1996 Nov 6;88(21):1529-42. link to original article PubMed
    2. Update: Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 2001 May 2;93(9):684-90. link to original article PubMed
    3. Update: Fisher B, Jeong JH, Bryant J, Anderson S, Dignam J, Fisher ER, Wolmark N; National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Treatment of lymph-node-negative, oestrogen-receptor-positive breast cancer: long-term findings from National Surgical Adjuvant Breast and Bowel Project randomised clinical trials. Lancet. 2004 Sep 4-10;364(9437):858-68. link to original article PubMed
    4. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed
  3. NSABP B-23: Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
    1. Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article PubMed
  4. NCIC CTG MA.17: Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. link to original article PubMed
    1. Update: Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. link to original article PubMed
    2. QoL analysis: Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005 Oct 1;23(28):6931-40. Epub 2005 Sep 12. link to original article PubMed
    3. Update: Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. link to original article PubMed
    4. Subgroup analysis: Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. link to original article PubMed
    5. Update: Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. link to original article link to PMC article PubMed
  5. NSABP B-33: Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. link to original article PubMed

Metastatic disease, maintenance after first-line therapy

Observation

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Regimen

Study Evidence Comparator Comparative Efficacy
Falkson et al. 1998 (INT-0077) Phase III (C) CMF(P)TH Inferior RFS
Sparano et al. 2004 (ECOG E2196) Phase III (C) Marimastat Did not meet primary endpoint of PFS
Alba et al. 2010 (GEICAM 2001-01) Phase III (C) PLD x 6 Inferior TTP
Park et al. 2013 (KCSG-BR07-02) Phase III (C) PG Seems to have inferior OS

No further treatment.

Preceding treatment

  • ECOG E2196: Doxorubicin- and/or taxane-containing chemotherapy x 6-8
  • GEICAM 2001-01: A x 3, then D x 3
  • KCSG-BR07-02: PG x 6

References

  1. INT-0077: Falkson G, Gelman RS, Pandya KJ, Osborne CK, Tormey D, Cummings FJ, Sledge GW, Abeloff MD. Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment. J Clin Oncol. 1998 May;16(5):1669-76. link to original article PubMed
  2. ECOG E2196: Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. link to original article PubMed
  3. GEICAM 2001-01: Alba E, Ruiz-Borrego M, Margelí M, Rodríguez-Lescure A, Sánchez-Rovira P, Ruiz A, Mel-Lorenzo JR, Ramos-Vázquez M, Ribelles N, Calvo E, Casado A, Márquez A, Vicente D, García-Sáenz JA, Martín M. Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. Breast Cancer Res Treat. 2010 Jul;122(1):169-76. Epub 2010 Apr 2. link to original article PubMed
  4. KCSG-BR07-02: Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
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