Difference between revisions of "Staging page"

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Breast_cancer|main breast cancer page]] for current regimens.
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Neoadjuvant therapy=
 
−
==CVAP {{#subobject:4a01b8|Regimen=1}}==
 
−
CVAP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin),  '''<u>P</u>'''rednisolone
 
−
<br>VACP: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7b4b85|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2002.20.6.1456 Smith et al. 2002]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.05.207 Thomas et al. 2004b]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisolone (Millipred)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div></div>
 
−
===References===
 
−
# Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002 Mar 15;20(6):1456-66. [https://doi.org/10.1200/JCO.2002.20.6.1456 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11896092 PubMed]
 
−
# Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, Singletary SE, Theriault RL, McNeese MD, Ames F, Walters R, Hortobagyi GN. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2294-302. [https://doi.org/10.1200/JCO.2004.05.207 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15197190/ PubMed]
 
−
=Adjuvant therapy, sequential protocols=
 
−
==FAC-MV {{#subobject:eb48eb|Regimen=1}}==
 
−
FAC-MV: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, followed by '''<u>M</u>'''ethotrexate & '''<u>V</u>'''inblastine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:883648|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.11396 Assikis et al. 2003]
 
−
|1986-1994
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, FAC portion====
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
====Chemotherapy, MV portion====
 
−
*[[Methotrexate (MTX)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vinblastine (Velban)]] 1.7 mg/m<sup>2</sup>/day continuous infusion over 120 hours, started on day 1 (total dose per cycle: 8.5 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] rescue
 
−
'''21- to 28-day cycle for 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [https://doi.org/10.1002/cncr.11396 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12767083 PubMed]
 
−
=Adjuvant therapy=
 
−
==ACT {{#subobject:4a01b8|Regimen=1}}==
 
−
ACT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''amoxifen
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 40/500/20 {{#subobject:7b46yg|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10147-013-0657-z Shien et al. 2014 (JCOG9401)]
 
−
|1994-1999
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143604/ Shien et al. 2014 (JCOG9404)]
 
−
|1994-1999
 
−
|style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#TUFT_88|TUFT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 6: 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 500 mg/m<sup>2</sup> IV once on day 1
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 20 mg PO once per day
 
−
'''28-day cycle for 6 cycles, then continuous for a total of 2 years'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 60/600/20 {{#subobject:7b4b85|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
 
−
|rowspan=2|1985-1988
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#PFT|PFT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day
 
−
'''21-day cycle for 4 cycles, then continuous for a total of 5 years'''
 
−
</div></div>
 
−
===References===
 
−
# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://doi.org/10.1200/JCO.1990.8.6.1005 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2189950/ PubMed]
 
−
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://doi.org/10.1200/JCO.2004.01.042 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15452182 PubMed]
 
−
# '''JCOG9401:''' Shien T, Iwata H, Aogi K, Fukutomi T, Inoue K, Kinoshita T, Takahashi M, Matsui A, Shibata T, Fukuda H. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol. 2014 Dec;19(6):982-8. Epub 2014 Jan 7. [https://doi.org/10.1007/s10147-013-0657-z link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24395447 PubMed]
 
−
# '''JCOG9404:''' Shien T, Iwata H, Fukutomi T, Inoue K, Aogi K, Kinoshita T, Ando J, Takashima S, Nakamura K, Shibata T, Fukuda H. Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology Group Study 9404. Cancer Chemother Pharmacol. 2014 Sep;74(3):603-9. Epub 2014 Jul 24. [https://doi.org/10.1007/s00280-014-2545-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143604/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25055938 PubMed]
 
−
==AVCF {{#subobject:4a0878|Regimen=1}}==
 
−
AVCF: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7b4c73|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.4.1136 Misset et al. 1996 (OncoFrance)]
 
−
|1978-1981
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# '''OncoFrance:''' Misset JL, di Palma M, Delgado M, Plagne R, Chollet P, Fumoleau P, Le Mevel B, Belpomme D, Guerrin J, Fargeot P, Metz R, Ithzaki M, Hill C, Mathé G. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996 Apr;14(4):1136-45. [https://doi.org/10.1200/JCO.1996.14.4.1136 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8648368 PubMed]
 
−
==AVCMF {{#subobject:4a3928|Regimen=1}}==
 
−
AVCMF: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''inblastine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7bcju3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.karger.com/Article/PDF/69831 Ploner et al. 2003 (ABCSG 3)]
 
−
|1984-NR
 
−
| style="background-color:#1a9851" |Randomized (E-RT-esc)
 
−
|[[Breast_cancer,_triple_negative#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of DFS/OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Vinblastine (Velban)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# '''ABCSG 3:''' Ploner F, Jakesz R, Hausmaninger H, Kolb R, Stierer M, Fridrik M, Steindorfer P, Gnant M, Haider K, Mlineritsch B, Tschurtschenthaler G, Steger G, Seifert M, Kubista E, Samonigg H; ABCSG. Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients. Onkologie. 2003 Apr;26(2):115-9. [https://doi.org/10.1159/000069831 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12771518 PubMed]
 
−
==CAMFP {{#subobject:4a01b8|Regimen=1}}==
 
−
CAMFP: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7b4b85|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199605233342102 Recht et al. 1996]
 
−
|1984-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Complex_multipart_regimens#Recht_et_al._1996|See link]]
 
−
|[[Complex_multipart_regimens#Recht_et_al._1996|See link]]
 
−
|-
 
−
|}
 
−
''Note: this was a trial examining sequencing of chemotherapy and radiotherapy; see text for efficacy details.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Lumpectomy|Lumpectomy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> PO four times per day on days 2 to 4, 16 to 18
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. [https://doi.org/10.1056/NEJM199605233342102 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8614420/ PubMed]
 
−
==CEF/CMF {{#subobject:682333|Regimen=1}}==
 
−
CEF/CMF: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil alternating with '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:3d1971|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202939/ Bedognetti et al. 2011]
 
−
|1985-1992
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CEFT.2FCMFT_99|CEFT/CMFT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, CEF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Epirubicin (Ellence)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Chemotherapy, CMF portion====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# Bedognetti D, Sertoli MR, Pronzato P, Del Mastro L, Venturini M, Taveggia P, Zanardi E, Siffredi G, Pastorino S, Queirolo P, Gardin G, Wang E, Monzeglio C, Boccardo F, Bruzzi P. Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial. J Natl Cancer Inst. 2011 Oct 19;103(20):1529-39. Epub 2011 Sep 15. [https://academic.oup.com/jnci/article/103/20/1529/905862 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202939/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21921285 PubMed]
 
−
==CFP {{#subobject:b514cd|Regimen=1}}==
 
−
CFP: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3b8f7d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(78)90678-5 Ahmann et al. 1978]
 
−
|NR
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Melphalan_monotherapy|Melphalan]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|rowspan=2|[https://jamanetwork.com/journals/jama/article-abstract/370748 Caprini et al. 1980]
 
−
|rowspan=2|1975-1979
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Melphalan_monotherapy|Melphalan]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|2. [[#CFP_.26_BCG_99|CFP & BCG]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Ahmann DL, Scanlon PW, Bisel HF, Edmonson JH, Frytak S, Payne WS, O'Fallon JR, Hahn RG, Ingle JN, O'Connell MJ, Rubin J. Repeated adjuvant chemotherapy with phenylalanine mustard or 5-fluorouracil, cyclophosphamide, and prednisone with or without radiation, after mastectomy for breast cancer. Lancet. 1978 Apr 29;1(8070):893-6. [https://doi.org/10.1016/S0140-6736(78)90678-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/76842 PubMed]
 
−
# Caprini JA, Oviedo MA, Cunningham MP, Cohen E, Trueheart RS, Khandekar JD, Scanlon EF. Adjuvant chemotherapy for stage II and III breast carcinoma. JAMA. 1980 Jul 18;244(3):243-6. [https://jamanetwork.com/journals/jama/article-abstract/370748 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6991733 PubMed]
 
−
==CFP & Oophorectomy {{#subobject:ba429d|Regimen=1}}==
 
−
CFP & Oophorectomy: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone & Bilateral Oophorectomy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:26519a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM197708182970704 Ahmann et al. 1977]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[#Oophorectomy|Oophorectomy]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], 3 weeks prior
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 150 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]] 30 mg PO once per day on days 1 to 7
 
−
*[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]]
 
−
'''35-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. [https://doi.org/10.1056/NEJM197708182970704 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/876327 PubMed]
 
−
==CMFL {{#subobject:1abd14|Regimen=1}}==
 
−
CMFL: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin (Folinic acid)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3dbcd1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198902233200804 Goldhirsch et al. 1989 (LCBS V)]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|No further treatment]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Mastectomy|Mastectomy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Folinic acid (Leucovorin)]]
 
−
'''8-day course'''
 
−
</div></div>
 
−
===References===
 
−
# '''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://doi.org/10.1056/NEJM198902233200804 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2644533 PubMed]
 
−
==CMFP {{#subobject:527931|Regimen=1}}==
 
−
CMFP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3feec0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q Tormey et al. 1990 (ECOG E5177)]
 
−
|1978-1982
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer#CMF|CMF]]<br>2. [[#CMFPT|CMFPT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of TTR/OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198809153191104 Goldhirsch et al. 1988 (IBCSG V)]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMFL|CMFL]] x 1
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198902233200803 Mansour et al. 1989 (INT-0011)]
 
−
|1981-1988
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|No further treatment]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
'''28-day cycle for 6 to 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''IBCSG V:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. [https://doi.org/10.1056/NEJM198809153191104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2901037 PubMed]
 
−
# '''ECOG E1180:''' 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://doi.org/10.1056/NEJM198902233200803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2915651 PubMed]
 
−
## '''Update:''' Mansour EG, Eudey L, Tormey DC, Shatila AH, Osborne CK, Gilchrist KW, Cooper MR, Falkson G. Chemotherapy versus observation in high-risk node-negative breast cancer patients. J Natl Cancer Inst Monogr. 1992;(11):97-104. [https://pubmed.ncbi.nlm.nih.gov/1627437 PubMed]
 
−
# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://doi.org/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q link to original article] [https://pubmed.ncbi.nlm.nih.gov/2403834 PubMed]
 
−
==CMFPT {{#subobject:204d9d|Regimen=1}}==
 
−
CMFPT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone, '''<u>T</u>'''amoxifen
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3a762a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan = 2|[https://doi.org/10.1016/S0140-6736(84)92445-0 Goldhirsch et al. 1984 (LBCS III)]
 
−
|rowspan=2|1978-1981
 
−
|rowspan = 2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|2. [[#PT|PT]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q Tormey et al. 1990 (ECOG E5177)]
 
−
|1978-1982
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer#CMF|CMF]]<br>2. [[#CMFP|CMFP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of TTR/OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198809153191104 Goldhirsch et al. 1988 (IBCSG V)]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMFL|CMFL]] x 1
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1990.8.4.599 Falkson et al. 1990]
 
−
|1982-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMFPT|CMFPT]] x 4
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
*[[Tamoxifen (Nolvadex)]]
 
−
'''28-day cycle for 6 to 12 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''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://doi.org/10.1016/S0140-6736(84)92445-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6144974 PubMed]
 
−
# '''IBCSG V:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. [https://doi.org/10.1056/NEJM198809153191104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2901037 PubMed]
 
−
# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://doi.org/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q link to original article] [https://pubmed.ncbi.nlm.nih.gov/2403834 PubMed]
 
−
# Falkson HC, Gray R, Wolberg WH, Gillchrist KW, Harris JE, Tormey DC, Falkson G; [[Study_Groups#ECOG|ECOG]]. Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study. J Clin Oncol. 1990 Apr;8(4):599-607. Erratum in: J Clin Oncol 1990 Sep;8(9):1603. [https://doi.org/10.1200/JCO.1990.8.4.599 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2179477 PubMed]
 
−
==CMFVP {{#subobject:ae7a82|Regimen=1}}==
 
−
CMFVP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:538cb7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O Glucksberg et al. 1982 (SWOG S7436)]
 
−
|1975-1978
 
−
|style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[#Melphalan_monotherapy|Melphalan]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1983.1.2.138 Tormey et al. 1983a]
 
−
|rowspan=2|1975-1980
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|[[#CMF-MER_77|CMF-MER]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1993.11.9.1710 Rivkin et al. 1993 (SWOG S7827<sub>ER-</sub>)]
 
−
|1979-1984
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMFVP|CMFVP]] x 2 y
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.1.46 Rivkin et al. 1996 (SWOG S7821)]
 
−
|1979-1989
 
−
|style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CMFVP_.26_Oophorectomy_99|CMFVP & Oophorectomy]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.5.1589 Perloff et al. 1996 (CALGB 8082)]
 
−
|1980-1984
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1995.13.4.831 Budd et al. 1995 (SWOG S8313)]
 
−
|1984-1990
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FAC-M_99|FAC-M]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# '''SWOG S7436:''' Glucksberg H, Rivkin SE, Rasmussen S, Tranum B, Gad-el-Mawla N, Costanzi J, Hoogstraten B, Athens J, Maloney T, McCracken J, Vaughn C. Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer. 1982 Aug 1;50(3):423-34. [https://doi.org/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O link to original article] [https://pubmed.ncbi.nlm.nih.gov/7046900/ PubMed]
 
−
## '''Update:''' Rivkin SE, Green SJ, Lew D, Costanzi JJ, Athens JW, Osborne CK, Vaughn CB, Martino S. Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a Southwest Oncology Group study. Cancer. 2003 Jan 1;97(1):21-9. [https://doi.org/10.1002/cncr.10982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12491501 PubMed]
 
−
# Tormey DC, Weinberg VE, Holland JF, Weiss RB, Glidewell OJ, Perloff M, Falkson G, Falkson HC, Henry PH, Leone LA, Rafla S, Ginsberg SJ, Silver RT, Blom J, Carey RW, Schein PS, Lesnick GJ. A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer. J Clin Oncol. 1983 Feb;1(2):138-45. [https://doi.org/10.1200/JCO.1983.1.2.138 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6366133 PubMed]
 
−
# '''SWOG S7827:''' Rivkin SE, Green S, Metch B, Jewell WR, Costanzi JJ, Altman SJ, Minton JP, O'Bryan RM, Osborne CK. One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study. J Clin Oncol. 1993 Sep;11(9):1710-6. [https://doi.org/10.1200/JCO.1993.11.9.1710 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8355037 PubMed]
 
−
# '''SWOG S8313:''' Budd GT, Green S, O'Bryan RM, Martino S, Abeloff MD, Rinehart JJ, Hahn R, Harris J, Tormey D, O'Sullivan J, Osborne CK. Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study. J Clin Oncol. 1995 Apr;13(4):831-9. [https://doi.org/10.1200/JCO.1995.13.4.831 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7707108 PubMed]
 
−
# '''SWOG S7821:''' Rivkin SE, Green S, O'Sullivan J, Cruz AB, Abeloff MD, Jewell WR, Costanzi JJ, Farrar WB, Osborne CK. Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study. J Clin Oncol. 1996 Jan;14(1):46-51. [https://doi.org/10.1200/JCO.1996.14.1.46 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8558219 PubMed]
 
−
# '''CALGB 8082:''' Perloff M, Norton L, Korzun AH, Wood WC, Carey RW, Gottlieb A, Aust JC, Bank A, Silver RT, Saleh F, Canellos GP, Perry MC, Weiss RB, Holland JF. Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study. J Clin Oncol. 1996 May;14(5):1589-98. [https://doi.org/10.1200/JCO.1996.14.5.1589 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622076 PubMed]
 
−
==CPB {{#subobject:0d159a|Regimen=1}}==
 
−
CPB: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''latinol (Cisplatin), '''<u>B</u>'''CNU (Carmustine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:683965|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2005.10.202 Peters et al. 2005 (CALGB 9082)]
 
−
|1991-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#High-dose_CPB.2C_then_auto_HSCT_99|HD-CPB with auto HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
''Note: this trial is of important historic significance. Although neither arm was standard of care, the results established the non-value of high-dose therapy with autologous HSCT in the adjuvant treatment of breast cancer.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FAC_2|FAC]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 900 mg/m<sup>2</sup> IV over 60 hours once per day on days 1 to 3
 
−
*[[Cisplatin (Platinol)]] 30 mg/mg<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose: 90 mg/m<sup>2</sup>)
 
−
*[[Carmustine (BCNU)]] 90 mg/m<sup>2</sup> IV over 18 hours once on day 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Breast_cancer#FAC_2|FAC]] x 1
 
−
</div></div>
 
−
===References===
 
−
# '''CALGB 9082:''' Peters WP, Rosner GL, Vredenburgh JJ, Shpall EJ, Crump M, Richardson PG, Schuster MW, Marks LB, Cirrincione C, Norton L, Henderson IC, Schilsky RL, Hurd DD. Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: a report of CALGB 9082, SWOG 9114, and NCIC MA-13. J Clin Oncol. 2005 Apr 1;23(10):2191-200. Epub 2005 Mar 14. [https://doi.org/10.1200/JCO.2005.10.202 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15767638 PubMed]
 
−
==CTCb, then auto HSCT {{#subobject:7a4fec|Regimen=1}}==
 
−
CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin
 
−
<br>STAMP-V
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9d0c8a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1990.8.7.1239 Eder et al. 1990]
 
−
|1987-1988
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(98)01350-6 Rodenhuis et al. 1998]
 
−
|1991-1995
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|Standard adjuvant therapy
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa022794 Rodenhuis et al. 2003 (Dutch National Study)]
 
−
|1993-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer#FEC_2|FEC]] x 5
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(00)02841-5 Bergh et al. 2000 (SBG 9401)]
 
−
|1994-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Complex_multipart_regimens#SBG_9401|See link]]
 
−
| style="background-color:#fc8d59" |[[Complex_multipart_regimens#SBG_9401|See link]]
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for the Dutch National Study is based on the 2020 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Rodenhuis et al. 1998: [[Breast_cancer#FEC|Neoadjuvant FEC]] x 3, then [[Surgery#Breast_cancer_surgery|surgery]], then [[Breast_cancer#FEC_2|FEC]] x 1
 
−
*Dutch National Study: [[Breast_cancer#FEC_2|FEC]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup>/day IV on days -7 to -4
 
−
*[[Thiotepa (Thioplex)]] 125 mg/m<sup>2</sup>/day IV on days -7 to -4
 
−
*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup>/day IV on days -7 to -4
 
−
'''Stem cells re-infused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
# Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. [https://doi.org/10.1200/jco.1990.8.7.1239 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2162912 PubMed]
 
−
# Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. [https://doi.org/10.1016/S0140-6736(98)01350-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9716055 PubMed]
 
−
# '''SBG 9401:''' Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. [https://doi.org/10.1016/s0140-6736(00)02841-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11052580/ PubMed]
 
−
# '''Dutch National Study:''' Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. [https://doi.org/10.1056/NEJMoa022794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12840087 PubMed] NCT03087409
 
−
## '''Update:''' Rodenhuis S, Bontenbal M, van Hoesel QG, Smit WM, Nooij MA, Voest EE, van der Wall E, Hupperets P, van Tinteren H, Peterse JL, van de Vijver MJ, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumours. Efficacy of high-dose alkylating chemotherapy in HER2/neu-negative breast cancer. Ann Oncol. 2006 Apr;17(4):588-96. Epub 2006 Jan 30. [https://doi.org/10.1093/annonc/mdl001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16446318/ PubMed]
 
−
## '''Update:''' Steenbruggen TG, Steggink LC, Seynaeve CM, van der Hoeven JJM, Hooning MJ, Jager A, Konings IR, Kroep JR, Smit WM, Tjan-Heijnen VCG, van der Wall E, Bins AD, Linn SC, Schaapveld M, Jacobse JN, van Leeuwen FE, Schröder CP, van Tinteren H, de Vries EGE, Sonke GS, Gietema JA. High-Dose Chemotherapy With Hematopoietic Stem Cell Transplant in Patients With High-Risk Breast Cancer and 4 or More Involved Axillary Lymph Nodes: 20-Year Follow-up of a Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Apr 1;6(4):528-534. [https://doi.org/10.1001/jamaoncol.2019.6276 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7042796/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31999296 PubMed]
 
−
==Cyclophosphamide monotherapy {{#subobject:7b2fec|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9d3c8a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=3|[https://doi.org/10.1007/BF01806239 Brinker et al. 1983 (DBCG 77B)]
 
−
|rowspan=3|1977-1983
 
−
|rowspan=3 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|2. [[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 
−
|-
 
−
|3. [[#Levamisole_monotherapy|Levamisole]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://doi.org/10.1016/j.breast.2009.09.006 Killander et al. 2009]
 
−
|1978-1983
 
−
|style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|1. [[#Radiation_therapy_88|RT]]<br>2. [[#Cyclophosphamide_.26_RT_88|Cyclophosphamide & RT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3228158/ Miles et al. 2011]
 
−
|1998-2003
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#STn-KLH_vaccine_77|STn-KLH vaccine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of TTP/OS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for DBCG 77B is based on the 2010 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
</div></div>
 
−
===References===
 
−
# '''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://doi.org/10.1007/BF01806239 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1002/cncr.24969 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20186830/ PubMed]
 
−
#Killander F, Anderson H, Rydén S, Möller T, Hafström LO, Malmström P. Efficient reduction of loco-regional recurrences but no effect on mortality twenty years after postmastectomy radiation in premenopausal women with stage II breast cancer - a randomized trial from the South Sweden Breast Cancer Group. Breast. 2009 Oct;18(5):309-15. Epub 2009 Oct 6. [https://doi.org/10.1016/j.breast.2009.09.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19811918/ PubMed]
 
−
# Miles D, Roché H, Martin M, Perren TJ, Cameron DA, Glaspy J, Dodwell D, Parker J, Mayordomo J, Tres A, Murray JL, Ibrahim NK; Theratope® Study Group. Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist. 2011;16(8):1092-100. Epub 2011 May 14. [https://doi.org/10.1634/theoncologist.2010-0307 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3228158/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21572124/ PubMed]
 
−
==ECT, then auto HSCT {{#subobject:7a4gab|Regimen=1}}==
 
−
ECT: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9d0a2n|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(05)67784-7 Nitz et al. 2005 (WSG AM-01)]
 
−
|1995-2002
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer#Dose-dense_Cyclophosphamide_.26_Epibicin_.28ddEC.29|ddEC]] x 4, then [[#Dose-dense_CMF_88|ddCMF]] x 3
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
''No longer used, but of historical interest.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Thiotepa (Thioplex)]]
 
−
</div></div>
 
−
===References===
 
−
# '''WSG AM-01:''' Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. [https://doi.org/10.1016/S0140-6736(05)67784-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16325695 PubMed]
 
−
==FAC & BCG {{#subobject:19f556|Regimen=1}}==
 
−
FAC & BCG: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, BCG
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:08e709|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/366766 Buzdar et al. 1979]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
====Immunotherapy====
 
−
*[[Bacillus Calmette-Guérin (BCG)]]
 
−
</div></div>
 
−
===References===
 
−
# Buzdar AU, Blumenschein GR, Gutterman JU, Tashima CK, Hortobagyi GN, Smith TL, Campos LT, Wheeler WL, Hersh EM, Freireich EJ, Gehan EA. Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine: a follow-up report. JAMA. 1979 Oct 5;242(14):1509-13. [https://jamanetwork.com/journals/jama/article-abstract/366766 link to original article] [https://pubmed.ncbi.nlm.nih.gov/470088 PubMed]
 
−
==Fluorouracil & Methotrexate (MF) {{#subobject:e1def3|Regimen=1}}==
 
−
MF: '''<u>M</u>'''ethotrexate & 5-'''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c6e0a3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/85/10/812/1024452 Shapiro et al. 1993]
 
−
|1976-1985
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of TTF/OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198902233200801 Fisher et al. 1989 (NSABP B-13)]
 
−
|1981-1988
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior DFS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.7.1982 Fisher et al. 1996 (NSABP B-19)]
 
−
|1988-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for NSABP B-13 is based on the 1996 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# '''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://doi.org/10.1056/NEJM198902233200801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1200/JCO.1996.14.7.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1200/JCO.2006.06.9054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16921044 PubMed]
 
−
# Shapiro CL, Gelman RS, Hayes DF, Osteen R, Obando A, Canellos GP, Frei E 3rd, Henderson IC. Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes. J Natl Cancer Inst. 1993 May 19;85(10):812-7. [https://academic.oup.com/jnci/article-abstract/85/10/812/1024452 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8487326 PubMed]
 
−
# '''NSABP B-19:''' 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://doi.org/10.1200/JCO.1996.14.7.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1200/JCO.2006.06.9054 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16921044 PubMed]
 
−
==FNC {{#subobject:152c11|Regimen=1}}==
 
−
FNC: '''<u>F</u>'''luorouracil, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>C</u>'''yclophosphamide
 
−
<br>CNF: '''<u>C</u>'''yclophosphamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:950f9d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1097/00000421-200108000-00001 Ron et al. 2001]
 
−
|1988-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer#CMF|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|[https://doi.org/10.1097/01.coc.0000046121.51504.b9 Fountzilas et al. 2004 (HE 10/92)]
 
−
|1992-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.07.8576 Toledano et al. 2007 (ARCOSEIN)]
 
−
|1996-2000
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FNC_.26_RT_99|FNC & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Lumpectomy|Breast-conserving surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*ARCOSEIN: [[Regimen_classes#Radiotherapy-based_regimen|RT]]
 
−
</div></div>
 
−
===References===
 
−
# Ron IG, Wigler N, Borovik R, Brufman G, Rizel S, Shani A, Brenner J, Farbstein H, Dale A, Inbar MJ, Brenner HJ, Chaitchik S, Catane R. CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast  cancer: a phase III randomized multicenter study. Am J Clin Oncol. 2001 Aug;24(4):323-7. [https://doi.org/10.1097/00000421-200108000-00001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11474254 PubMed]
 
−
# '''HE 10/92:''' Fountzilas G, Stathopoulos G, Kouvatseas G, Polychronis A, Klouvas G, Samantas E, Zamboglou N, Kyriakou K, Adamou A, Pectasidis D, Ekonomopoulos T, Kalofonos HP, Bafaloukos D, Georgoulias V, Razis E, Koukouras D, Zombolas V, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Adjuvant cytotoxic and endocrine therapy in pre- and postmenopausal patients with breast cancer and one to nine infiltrated nodes: five-year results of the Hellenic Cooperative Oncology Group randomized HE 10/92 study. Am J Clin Oncol. 2004 Feb;27(1):57-67. [https://doi.org/10.1097/01.coc.0000046121.51504.b9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14758135 PubMed]
 
−
# '''ARCOSEIN:''' Toledano A, Azria D, Garaud P, Fourquet A, Serin D, Bosset JF, Miny-Buffet J, Favre A, Le Floch O, Calais G. Phase III trial of concurrent or sequential adjuvant chemoradiotherapy after conservative surgery for early-stage breast cancer: final results of the ARCOSEIN trial. J Clin Oncol. 2007 Feb 1;25(4):405-10. Erratum in: J Clin Oncol. 2007 Jun 1;25(16):2334. [https://doi.org/10.1200/JCO.2006.07.8576 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17264336 PubMed]
 
−
==Levamisole monotherapy {{#subobject:b051c5|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ec3553|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(76)91337-4 Rojas et al. 1976]
 
−
|NR
 
−
|style="background-color:#1a9851"|Randomized (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(80)90173-7 Brincker et al. 1980]
 
−
|NR
 
−
|style="background-color:#1a9851"|Randomized (E-switch-ooc)
 
−
|[[#Radiation_therapy_88|RT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|}
 
−
''Note: Rojas et al. 1976 included patients with inoperable breast cancer; definitive therapy was RT.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Rojas et al. 1976: [[Regimen_classes#Radiotherapy-based_regimen|Radiotherapy]]
 
−
*Brincker et al. 1980: [[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Levamisole (Ergamisol)]]
 
−
</div></div>
 
−
===References===
 
−
# Rojas AF, Feierstein JN, Mickiewicz E, Glait H, Olivari AJ. Levamisole in advanced human breast cancer. Lancet. 1976 Jan 31;1(7953):211-5. [https://doi.org/10.1016/S0140-6736(76)91337-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/55529 PubMed]
 
−
# Brincker H, Mouridsen HT, Andersen KW, Andersen J, Castberg T, Fischermann K, Henriksen E, Hou-Jensen C, Johansen H, Rossing N, Rorth M; Danish Breast Cancer Cooperative Group. Increased breast-cancer recurrence rate after adjuvant therapy with levamisole: a preliminary report. Lancet. 1980 Oct 18;2(8199):824-7. [https://doi.org/10.1016/S0140-6736(80)90173-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6107500/ PubMed]
 
−
==Melphalan monotherapy {{#subobject:b062c5|Regimen=1}}==
 
−
P: '''<u>P</u>'''henylalanine mustard (Melphalan)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ec3663|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM197501162920301 Fisher et al. 1975 (NSABP B-05)]
 
−
|1972-1975
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 Fisher et al. 1977 (NSABP B-07)]
 
−
|1975-1976
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PF|PF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior RFS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O Glucksberg et al. 1982 (SWOG S7436)]
 
−
|1975-1978
 
−
|style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CMFVP|CMFVP]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(83)91385-5 Rubens et al. 1983]
 
−
|1975-1979
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior RFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for NSABP B-05 is based on the 1986 update.''<br>
 
−
''Note: Fisher et al. 1977 is an update for NSABP B-05 and also the primary results for NSABP B-07.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]]
 
−
</div></div>
 
−
===References===
 
−
# '''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://doi.org/10.1056/NEJM197501162920301 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1002/1097-0142(197706)39:6%3C2883::AID-CNCR2820390676%3E3.0.CO;2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1200/JCO.1986.4.6.929 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3519883 PubMed]
 
−
# '''NSABP B-07:''' 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://doi.org/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/194679 PubMed]
 
−
# '''SWOG S7436:''' Glucksberg H, Rivkin SE, Rasmussen S, Tranum B, Gad-el-Mawla N, Costanzi J, Hoogstraten B, Athens J, Maloney T, McCracken J, Vaughn C. Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer. 1982 Aug 1;50(3):423-34. [https://doi.org/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O link to original article] [https://pubmed.ncbi.nlm.nih.gov/7046900/ PubMed]
 
−
## '''Update:''' Rivkin SE, Green SJ, Lew D, Costanzi JJ, Athens JW, Osborne CK, Vaughn CB, Martino S. Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a Southwest Oncology Group study. Cancer. 2003 Jan 1;97(1):21-9. [https://doi.org/10.1002/cncr.10982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12491501 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://doi.org/10.1016/S0140-6736(83)91385-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6132179 PubMed]
 
−
==Oophorectomy==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM197708182970704 Ahmann et al. 1977]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CFP_.26_Oophorectomy|CFP & Oophorectomy]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5052674/ Love et al. 2016 (OSU-0476)]
 
−
|2004-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Endocrine_ablation_surgery#Bilateral_oophorectomy_99|Mid-luteal phase oophorectomy]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*OSU-0476: [[#Tamoxifen_monotherapy_88|Tamoxifen]]
 
−
</div></div>
 
−
===References===
 
−
# Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. [https://doi.org/10.1056/NEJM197708182970704 link to original article] [https://pubmed.ncbi.nlm.nih.gov/876327 PubMed]
 
−
# '''OSU-0476:''' Love RR, Hossain SM, Hussain MM, Mostafa MG, Laudico AV, Siguan SS, Adebamowo C, Sun JZ, Fei F, Shao ZM, Liu Y, Akram Hussain SM, Zhang B, Cheng L, Panigaro S, Walta F, Chuan JH, Mirasol-Lumague MR, Yip CH, Navarro NS Jr, Huang CS, Lu YS, Ferdousy T, Salim R, Akhter C, Nahar S, Uy G, Young GS, Hade EM, Jarjoura D. Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor-positive breast cancer. Eur J Cancer. 2016 Jun;60:107-16. Epub 2016 Apr 20. [https://doi.org/10.1016/j.ejca.2016.03.011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5052674/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27107325/ PubMed] NCT00293540
 
−
==Paclitaxel monotherapy, q3wk {{#subobject:1cb87f|Regimen=1}}==
 
−
T: '''<u>T</u>'''axol (Paclitaxel)
 
−
<br>P: '''<u>P</u>'''aclitaxel
 
−
<br>pT: '''<u>p</u>'''acli'''<u>T</u>'''axel
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 175 mg/m<sup>2</sup> q3wk {{#subobject:c084f5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2003.02.063 Henderson et al. 2003 (INT 0148/CALGB 9344)]
 
−
|1994-1999
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
''Note: 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.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*INT 0148/CALGB 9344: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4 versus [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; high-dose x 4 versus [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]]; very-high-dose x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# '''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. [https://doi.org/10.1200/jco.2003.02.063 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12637460/ PubMed]
 
−
==PAF {{#subobject:5750af|Regimen=1}}==
 
−
PAF: '''<u>P</u>'''henylalanine mustard (Melphalan), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:763980|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1989.7.5.572 Fisher et al. 1989 (NSABP B-11)]
 
−
|1981-1984
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#PF|PF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# '''NSABP B-11:''' Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. [https://doi.org/10.1200/JCO.1989.7.5.572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2651576 PubMed]
 
−
==PF {{#subobject:3a5d5f|Regimen=1}}==
 
−
PF: '''<u>P</u>'''henylalanine mustard (Melphalan) & '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:06f47d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 Fisher et al. 1977 (NSABP B-07)]
 
−
|1975-1976
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Melphalan_monotherapy|P]]
 
−
| style="background-color:#91cf60" |Seems to have superior RFS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19800815)46:4%2B%3C1009::AID-CNCR2820461326%3E3.0.CO;2-H Fisher et al. 1980 (NSABP B-08)]
 
−
|1976-1977
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PFM_99|PFM]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198107023050101 Fisher et al. 1981 (NSABP B-09)]
 
−
|1977-1980
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PFT|PFT]]
 
−
| style="background-color:#d73027" |Inferior RFS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142%2819900715)66%3A2%3C220%3A%3AAID-CNCR2820660205%3E3.0.CO%3B2-6 Fisher et al. 1990 (NSABP B-10)]
 
−
|1977-1981
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PFCp_99|PFCp]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoints of DFS/OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1989.7.5.572 Fisher et al. 1989 (NSABP B-11)]
 
−
|1981-1984
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#PAF|PAF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
''Note: Fisher et al. 1980 is more of a meta-analysis than a primary publication, but is to our knowledge the first manuscript to report the findings from NSABP B-08, which was a negative trial.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# '''NSABP B-07:''' 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://doi.org/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/194679 PubMed]
 
−
# '''NSABP B-08:''' Fisher B, Redmond C, Fisher ER. The contribution of recent NSABP clinical trials of primary breast cancer therapy to an understanding of tumor biology--an overview of findings. Cancer. 1980 Aug 15;46(4 Suppl):1009-25. [https://doi.org/10.1002/1097-0142(19800815)46:4%2B%3C1009::AID-CNCR2820461326%3E3.0.CO;2-H link to original article] [https://pubmed.ncbi.nlm.nih.gov/6994873 PubMed]
 
−
# '''NSABP B-09:''' Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. [https://doi.org/10.1056/NEJM198107023050101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7015139 PubMed]
 
−
## '''Update:''' Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. [https://doi.org/10.1200/JCO.1986.4.4.459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2856857 PubMed]
 
−
## '''Update:''' Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. [https://doi.org/10.7326/0003-4819-106-5-649 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3551710/ PubMed]
 
−
# '''NSABP B-11:''' Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. [https://doi.org/10.1200/JCO.1989.7.5.572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2651576 PubMed]
 
−
# '''NSABP B-10:''' Fisher B, Brown A, Wolmark N, Fisher ER, Redmond C, Wickerham DL, Margolese R, Dimitrov N, Pilch Y, Glass A, Sutherland C, Foster R. Evaluation of the worth of corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer: eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10. Cancer. 1990 Jul 15;66(2):220-7. [https://doi.org/10.1002/1097-0142%2819900715)66%3A2%3C220%3A%3AAID-CNCR2820660205%3E3.0.CO%3B2-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2196108 PubMed]
 
−
==PFT {{#subobject:1cb87f|Regimen=1}}==
 
−
PFT: '''<u>P</u>'''henylalanine mustard (Melphalan), 5-'''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c084f5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198107023050101 Fisher et al. 1981 (NSABP B-09)]
 
−
|1977-1980
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#PF|PF]]
 
−
| style="background-color:#1a9850" |Superior RFS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
 
−
|rowspan=2|1985-1988
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#ACT|ACT]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior DDFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Breast_cancer_surgery|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]]
 
−
</div></div>
 
−
===References===
 
−
# '''NSABP B-09:''' Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. [https://doi.org/10.1056/NEJM198107023050101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7015139 PubMed]
 
−
## '''Update:''' Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. [https://doi.org/10.1200/JCO.1986.4.4.459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2856857 PubMed]
 
−
## '''Update:''' Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. [https://doi.org/10.7326/0003-4819-106-5-649 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3551710/ PubMed]
 
−
# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://doi.org/10.1200/JCO.1990.8.6.1005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2189950/ PubMed]
 
−
## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://doi.org/10.1200/JCO.2004.01.042 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15452182 PubMed]
 
−
==PT {{#subobject:c08464|Regimen=1}}==
 
−
PT: '''<u>P</u>'''rednisone & '''<u>T</u>'''amoxifen
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2fc709|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan = 2|[https://doi.org/10.1016/S0140-6736(84)92445-0 Goldhirsch et al. 1984 (LBCS III)]
 
−
|rowspan=2|1978-1981
 
−
|rowspan = 2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#CMFPT|CMFPT]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|2. [[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(84)92445-0 Goldhirsch et al. 1984 (LBCS IV)]
 
−
|1978-1981
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Mastectomy|Mastectomy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
*[[Tamoxifen (Nolvadex)]]
 
−
</div></div>
 
−
===References===
 
−
# '''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://doi.org/10.1016/S0140-6736(84)92445-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6144974 PubMed]
 
−
==Thiotepa monotherapy {{#subobject:1cbc64|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9fac12|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387335/ Fisher et al. 1968 (NSABP B-01)]
 
−
|1958-1961
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Placebo_88|Placebo]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Thiotepa (Tepadina)]]
 
−
</div></div>
 
−
===References===
 
−
# '''NSABP B-01:''' Fisher B, Ravdin RG, Ausman RK, Slack NH, Moore GE, Noer RJ. Surgical adjuvant chemotherapy in cancer of the breast: results of a decade of cooperative investigation. Ann Surg. 1968 Sep;168(3):337-56. [https://doi.org/10.1097/00000658-196809000-00004 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387335/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/4970947 PubMed]
 
−
## '''Update:''' Fisher B, Slack N, Katrych D, Wolmark N. Ten year follow-up results of patients with carcinoma of the breast in a co-operative clinical trial evaluating surgical adjuvant chemotherapy. Surg Gynecol Obstet. 1975 Apr;140(4):528-34. [https://pubmed.ncbi.nlm.nih.gov/805475 PubMed]
 
−
==TMF {{#subobject:c08464|Regimen=1}}==
 
−
TMF: '''<u>T</u>'''hiotepa, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2fc709|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Dates of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a058929 Semiglazov et al. 1994]
 
−
|1985-1990
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#TMF|TMF]], then [[Regimen_classes#Radiotherapy-based_regimen|RT]] versus [[Regimen_classes#Radiotherapy-based_regimen|RT]], then [[Surgery#Mastectomy|Mastectomy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Thiotepa (Thioplex)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# Semiglazov VF, Topuzov EE, Bavli JL, Moiseyenko VM, Ivanova OA, Seleznev IK, Orlov AA, Barash NY, Golubeva OM, Chepic OF. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994 Sep;5(7):591-5. [https://doi.org/10.1093/oxfordjournals.annonc.a058929 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7993833 PubMed]
 
−
=Metastatic disease, all lines of therapy=
 
−
==Aminoglutethimide monotherapy {{#subobject:821a2c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f62b32|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(78)92759-9 Smith et al. 1978]
 
−
|1977-1978
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198109033051003 Santen et al. 1981]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (E-switch-ic)
 
−
|[[Endocrine_ablation_surgery#Bilateral_adrenalectomy_88|Bilateral adrenalectomy]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(84)90596-8 Stuart-Harris et al. 1984]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 Canney et al. 1988]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[#Medroxyprogesterone_monotherapy|MPA]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1007/BF01810736 Lundgren et al. 1989]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1007/BF01961246 Garcia-Giralt et al. 1992]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Medroxyprogesterone_monotherapy|MPA]]
 
−
| style="background-color:#91cf60" |Seems to have superior TTP
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/8135469 Robustelli della Cuna et al. 1993]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]; higher-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J Gale et al. 1994]
 
−
|1977-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]<br>2. [[Endocrine_ablation_surgery#Bilateral_adrenalectomy_88|Bilateral adrenalectomy]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DOR/TTF/OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Aminoglutethimide (Cytadren)]]
 
−
====Supportive therapy====
 
−
*[[Hydrocortisone (Cortef)]]
 
−
</div></div>
 
−
===References===
 
−
# Smith IE, Fitzharris BM, McKinna JA, Fahmy DR, Nash AG, Neville AM, Gazet JC, Ford HT, Powles TJ. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646-9. [https://doi.org/10.1016/S0140-6736(78)92759-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/80576 PubMed]
 
−
# Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA. A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Engl J Med. 1981 Sep 3;305(10):545-51. [https://doi.org/10.1056/NEJM198109033051003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7019703 PubMed]
 
−
# Stuart-Harris R, Dowsett M, Bozek T, McKinna JA, Gazet JC, Jeffcoate SL, Kurkure A, Carr L, Smith IE. Low-dose aminoglutethimide in treatment of advanced breast cancer. Lancet. 1984 Sep 15;2(8403):604-7. [https://doi.org/10.1016/S0140-6736(84)90596-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6147642 PubMed]
 
−
# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. [https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2970555 PubMed]
 
−
# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. [https://doi.org/10.1007/BF01810736 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2690972 PubMed]
 
−
# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. [https://doi.org/10.1007/BF01961246 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8443401 PubMed]
 
−
# Robustelli della Cuna G, Pannuti F, Martoni A, Camaggi CM, Strocchi E, Da Prada GA, Tanneberger S; Italian Cooperative Group. Aminoglutethimide in advanced breast cancer: prospective, randomized comparison of two dose levels. Anticancer Res. 1993 Nov-Dec;13(6B):2367-71. [https://pubmed.ncbi.nlm.nih.gov/8135469 PubMed]
 
−
# Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ; [[Study_Groups#ECOG|ECOG]]. Hormonal treatment for metastatic breast cancer: an Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer. 1994 Jan 15;73(2):354-61. [https://doi.org/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J link to original article] [https://pubmed.ncbi.nlm.nih.gov/8293400/ PubMed]
 
−
==CAMF {{#subobject:4b99b8|Regimen=1}}==
 
−
CAMF: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
<br>AFCM: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7c9b85|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q Tranum et al. 1978]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[#Doxorubin_.26_Fluorouracil_.28FA.29_88|AF]]<br>2. [[Breast_cancer#FAC_3|FAC]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D Bezwoda et al. 1979]
 
−
|1976-1977
 
−
|style="background-color:#1a9851" |Randomized (E-switch-ic)
 
−
|[[#CMFV|CMFV]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1984.2.1.28 Lippman et al. 1984]
 
−
|1977-1982
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CAMFTP_99|CAMFTP]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
</div></div>
 
−
===References===
 
−
# Tranum B, Hoogstraten B, Kennedy A, Vaughn CB, Samal B, Thigpen T, Rivkin S, Smith F, Palmer RL, Costanzi J, Tucker WG, Wilson H, Maloney TR; [[Study_Groups#SWOG|SWOG]]. Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study. Cancer. 1978 Jun;41(6):2078-83. [https://doi.org/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q link to original article] [https://pubmed.ncbi.nlm.nih.gov/657081 PubMed]
 
−
# Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. [https://doi.org/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D link to original article] [https://pubmed.ncbi.nlm.nih.gov/383254 PubMed]
 
−
# Lippman ME, Cassidy J, Wesley M, Young RC. A randomized attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization. J Clin Oncol. 1984 Jan;2(1):28-36. [https://doi.org/10.1200/JCO.1984.2.1.28 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6321686 PubMed]
 
−
==CAF & MPA {{#subobject:6c7ff9|Regimen=1}}==
 
−
CAF & MPA: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>M</u>'''edroxy'''<u>P</u>'''rogesterone '''<u>A</u>'''cetate
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b2ce67|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/0959-8049(94)90123-6 Tominaga et al. 1994]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer#FAC_3|CAF]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Medroxyprogesterone (MPA)]]
 
−
</div></div>
 
−
===References===
 
−
# Tominaga T, Abe O, Ohshima A, Hayasaka H, Uchino J, Abe R, Enomoto K, Izuo M, Watanabe H, Takatani O, Yoshida M, Sakai K, Koyama H, Hattori T, Senoo T, Monden Y, Nomura Y. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer. 1994;30A(7):959-64. [https://doi.org/10.1016/0959-8049(94)90123-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7946592 PubMed]
 
−
==CAFVP {{#subobject:918bda|Regimen=1}}==
 
−
CAFVP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e01caf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 Muss et al. 1978]
 
−
|1975-1976
 
−
|style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CMFVP_2|CMFVP]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1987.5.10.1523 Aisner et al. 1987]
 
−
|rowspan=2|1976-1980
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Breast_cancer#FAC_3|CAF]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[Breast_cancer#CMF_2|CMF]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. [https://doi.org/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/363253 PubMed]
 
−
# Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; [[Study_Groups#CALGB|CALGB]]. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. [https://doi.org/10.1200/JCO.1987.5.10.1523 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3655855 PubMed]
 
−
==CAV {{#subobject:90f8d0|Regimen=1}}==
 
−
CAV: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine
 
−
<br>VAC: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4da860|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19821201)50:11%3C2269::aid-cncr2820501107%3E3.0.co;2-l Muss et al. 1982]
 
−
|1979-1981
 
−
|style="background-color:#1a9851"|Randomized (E-esc)
 
−
|[[Breast_cancer#CMF_2|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19841201)54:11%3C2338::aid-cncr2820541105%3E3.0.co;2-4 Zekan et al. 1984]
 
−
|1981-1982
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#High-dose_Cyclophosphamide_.26_Fluorouracil_99|CF]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoints
 
−
|-
 
−
|[https://doi.org/10.1016/0277-5379(86)90075-1 Gundersen et al. 1986]
 
−
|1982-1983
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Breast_cancer#Doxorubicin_monotherapy_2|Doxorubicin]]
 
−
|style="background-color:#ffffbf"|Did not meet endpoint of ORR
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977504/ Powles et al. 1991]
 
−
|1985-1989
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Stub#3M|3M]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1007/BF01806182 Green et al. 1996]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Stub#VNC|VNC]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
</div></div>
 
−
===References===
 
−
# Muss HB, Richards F 2nd, Jackson DV, Cooper MR, White DR, Stuart JJ, Ramseur W, Christian RM, Wells HB, Pope E, Spurr CL; Piedmont Oncology Association. Vincristine, doxorubicin, and cyclophosphamide versus low-dose intravenous cyclophosphamide, methotrexate, and 5-fluorouracil in advanced breast cancer: a randomized trial of the Piedmont Oncology Association. Cancer. 1982 Dec 1;50(11):2269-74. [https://doi.org/10.1002/1097-0142(19821201)50:11%3C2269::aid-cncr2820501107%3E3.0.co;2-l link to original article] [https://pubmed.ncbi.nlm.nih.gov/6754062 PubMed]
 
−
# Zekan PJ, Muss HB, Capizzi RL, Cooper MR, Harding RW, Hopkins JO, Jackson DV, Ramseur WL, Richards F 2nd, Spurr CL, Stuart JJ, White DR, Pope E, Case D, Wells HB; Piedmont Oncology Association. High-dose cyclophosphamide and 5-fluorouracil versus vincristine, doxorubicin, and cyclophosphamide in advanced carcinoma of the breast: a phase III study of the Piedmont Oncology Association (POA). Cancer. 1984 Dec 1;54(11):2338-43. [https://doi.org/10.1002/1097-0142(19841201)54:11%3C2338::aid-cncr2820541105%3E3.0.co;2-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6388802 PubMed]
 
−
# Gundersen S, Kvinnsland S, Klepp O, Kvaløy S, Lund E, Høst H. Weekly adriamycin versus VAC in advanced breast cancer: a randomized trial. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1431-4. [https://doi.org/10.1016/0277-5379(86)90075-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3595668 PubMed]
 
−
# Powles TJ, Jones AL, Judson IR, Hardy JR, Ashley SE. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J Cancer. 1991 Aug;64(2):406-10. [https://doi.org/10.1038/bjc.1991.318 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977504/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/1892775 PubMed]
 
−
# Green JA, Slater AJ, Campbell IR, Kelly V. Advanced breast cancer: a randomized study of doxorubicin or mitoxantrone in combination with cyclophosphamide and vincristine. Breast Cancer Res Treat. 1996;39(2):155-63. [https://doi.org/10.1007/BF01806182 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8872324 PubMed]
 
−
==CFP {{#subobject:ba429d|Regimen=1}}==
 
−
CFP: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:26519a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1984.2.11.1260 Creagan et al. 1984]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CAP_99|CAP]], then [[#CFP_2|CFP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|CA]]<br>2. [[#CMFVP_2|CMFVP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F Marschke et al. 1989]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CMFP_2|CMFP]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Creagan ET, Green SJ, Ahmann DL, Ingle JN, Edmonson JH, Marschke RF Jr. A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer. J Clin Oncol. 1984 Nov;2(11):1260-5. [https://doi.org/10.1200/JCO.1984.2.11.1260 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6387059 PubMed]
 
−
# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://doi.org/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] [https://pubmed.ncbi.nlm.nih.gov/3815266 PubMed]
 
−
# Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. [https://doi.org/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F link to original article] [https://pubmed.ncbi.nlm.nih.gov/2649221 PubMed]
 
−
==Chlorambucil & Prednisolone {{#subobject:2cde9a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0044a9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/1163685 Freckman et al. 1964]
 
−
|1955-1963
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|rowspan=2|[https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%2819831101%2952%3A9%3C1570%3A%3AAID-CNCR2820520905%3E3.0.CO%3B2-W Løber et al. 1983]
 
−
|rowspan=2|1978-1980
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Prednimustine_monotherapy_88|Prednimustine]]; continuous
 
−
| style="background-color:#d73027" |Inferior TTP
 
−
|-
 
−
|2. [[#Prednimustine_monotherapy_88|Prednimustine]]; intermittent
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Chlorambucil (Leukeran)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisolone (Millipred)]]
 
−
</div></div>
 
−
===References===
 
−
# Freckman HA, Fry HL, Mendez FL, Maurer ER. Chlorambucil-prednisolone therapy for disseminated breast carcinoma. JAMA. 1964 Jul 6;189:23-6. [https://jamanetwork.com/journals/jama/article-abstract/1163685 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14149018 PubMed]
 
−
# Løber J, Mouridsen HT, Christiansen IE, Dombernowsky P, Mattsson W, Rørth M. A phase III trial comparing prednimustine (LEO 1031) to chlorambucil plus prednisolone in advanced breast cancer. Cancer. 1983 Nov 1;52(9):1570-6. [https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/1097-0142%2819831101%2952%3A9%3C1570%3A%3AAID-CNCR2820520905%3E3.0.CO%3B2-W link to original article] [https://pubmed.ncbi.nlm.nih.gov/6352005 PubMed]
 
−
==CHUT, then auto HSCT {{#subobject:e9e363|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:392c1c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1038/sj.bmt.1705935 Biron et al. 2007 (Pegase 03)]
 
−
|1995-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation_2|No further treatment]]
 
−
| style="background-color:#1a9850" |Superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Breast_cancer#FEC_3|FEC]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup>
 
−
*[[Thiotepa (Thioplex)]] 800 mg/m<sup>2</sup>
 
−
</div></div>
 
−
===References===
 
−
# '''Pegase 03:''' Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. [https://doi.org/10.1038/sj.bmt.1705935 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18037940/ PubMed] NCT00002870
 
−
==CMFP {{#subobject:d1eccf|Regimen=1}}==
 
−
CMFP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6c96a9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633086/ Canellos et al. 1974]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1007/BF01806026 Segaloff et al. 1985]
 
−
|1971-1976
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMFVP_2|CMFVP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L Tormey et al. 1982 (ECOG E2173)]
 
−
|1973-1974
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[#Doxorubicin_.26_Vinblastine_.28AV.29_88|AV]]<br>2. [[Breast_cancer#CMF_2|CMF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1985.3.7.932 Cummings et al. 1985]
 
−
|1978-1979
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[Breast_cancer#FAC_3|CAF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F Marschke et al. 1989]
 
−
|1982-1987
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[#CFP_2|CFP]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.8.2355 Bishop et al. 1999]
 
−
|1993-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Canellos GP, Devita VT, Gold GL, Chabner BA, Schein PS, Young RC. Cyclical combination chemotherapy for advanced breast carcinoma. Br Med J. 1974 Feb 9;1(5901):218-20. [https://doi.org/10.1136/bmj.1.5901.218 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633086/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/4818162 PubMed]
 
−
# '''ECOG E2173:''' Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, DeWys W, Perlia C, Rice MA. Comparison of induction chemotherapies for metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Cancer. 1982 Oct 1;50(7):1235-44. [https://doi.org/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L link to original article] [https://pubmed.ncbi.nlm.nih.gov/7049347 PubMed]
 
−
# Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. [https://doi.org/10.1007/BF01806026 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3896353 PubMed]
 
−
# Cummings FJ, Gelman R, Horton J. Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors. J Clin Oncol. 1985 Jul;3(7):932-40. [https://doi.org/10.1200/JCO.1985.3.7.932 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3894587 PubMed]
 
−
# Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. [https://doi.org/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F link to original article] [https://pubmed.ncbi.nlm.nih.gov/2649221 PubMed]
 
−
# Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, Ackland S, Kennedy I, Goldstein D, Gurney H, Walpole E, Levi J, Stephenson J, Canetta R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355-64. [https://doi.org/10.1200/JCO.1999.17.8.2355 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10561297 PubMed]
 
−
==CMFV {{#subobject:e18ffa|Regimen=1}}==
 
−
CMFV: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''inblastine
 
−
<br>CVMF: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''inblastine, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:405835|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(75)90676-5 Edelstyn et al. 1975]
 
−
|NR
 
−
|style="background-color:#1a9851" |Randomized (E-esc)
 
−
|[[#CMFV|CMFV]]; 1-day
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D Bezwoda et al. 1979]
 
−
|1976-1977
 
−
|style="background-color:#1a9851" |Randomized (C)
 
−
|[[#CAMF|CAMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
</div></div>
 
−
===References===
 
−
# Edelstyn GA, Bates TD, Brinkley D, MacRae KD, Spittle MF, Wheeler T. Comparison of 5-day, 1-day, and 2-day cyclical combination chemotherapy in advanced breast cancer. Lancet. 1975 Aug 2;2(7927):209-11. [https://doi.org/10.1016/s0140-6736(75)90676-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/51964 PubMed]
 
−
# Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. [https://doi.org/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D link to original article] [https://pubmed.ncbi.nlm.nih.gov/383254 PubMed]
 
−
==CMFVP {{#subobject:9920da|Regimen=1}}==
 
−
CMFVP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<br>COMFP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
 
−
<br>CFPMV: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''incristine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e01cbf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/BF01806026 Segaloff et al. 1985]
 
−
|1971-1976
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#CMFP_2|CMFP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 Hoogstraten et al. 1976]
 
−
|1972-1974
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer#Doxorubicin_monotherapy_3|Doxorubicin]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M Smalley et al. 1977]
 
−
|1974-1975
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer#FAC_3|CAF]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 Muss et al. 1978]
 
−
|1975-1976
 
−
|style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CAFVP|CAFVP]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/0014-2964(80)90037-7 Carmo-Pereira et al. 1980]
 
−
|NR
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Fluorouracil_monotherapy_88|5-FU]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
 
−
|1981-1985
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_3|CA]]<br>2. [[#CFP_2|CFP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for Smalley et al. 1977 is based on the 1983 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Fluorouracil (5-FU)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisone (Sterapred)]]
 
−
</div></div>
 
−
===References===
 
−
# Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H; [[Study_Groups#SWOG|SWOG]]. Combination chemotherapy and adriamycin in patients with advanced breast cancer: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):13-20. [https://doi.org/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/947510/ PubMed]
 
−
# Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S; Southeastern Cancer Study Group. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. [https://doi.org/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/329975 PubMed]
 
−
## '''Update:''' Smalley RV, Lefante J, Bartolucci A, Carpenter J, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer. Breast Cancer Res Treat. 1983;3(2):209-20. [https://doi.org/10.1007/BF01803563 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6688538 PubMed]
 
−
# Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. [https://doi.org/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/363253 PubMed]
 
−
# Carmo-Pereira J, Costa FO, Henriques E. Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: a randomized study. Eur J Cancer. 1980 Dec;16(12):1621-5. [https://doi.org/10.1016/0014-2964(80)90037-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7014228 PubMed]
 
−
# Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. [https://doi.org/10.1007/BF01806026 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3896353 PubMed]
 
−
# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://doi.org/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] [https://pubmed.ncbi.nlm.nih.gov/3815266 PubMed]
 
−
==DES monotherapy {{#subobject:0a1860|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:128a40|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/14285946 Kennedy 1965]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Randomized (E-switch-ic)
 
−
|[[#Testosterone_monotherapy_88|Testosterone]]
 
−
| style="background-color:#d3d3d3" |Not available
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/article-abstract/353009 Carter et al. 1977]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#DES_monotherapy|DES]]; other dosings
 
−
| style="background-color:#d3d3d3" |See paper
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19810201)47:3%3C452::AID-CNCR2820470305%3E3.0.CO;2-Y Kiang et al. 1981]
 
−
|1975-1982
 
−
| style="background-color:#1a9851" |Randomized (C)
 
−
|[[#Cyclophosphamide.2C_DES.2C_Fluorouracil_88|Cyclophosphamide, 5-FU, DES]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198101013040104 Ingle et al. 1981]
 
−
|1977-1980
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for Kiang et al. 1981 is based on the 1985 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Diethylstilbestrol (DES)]]
 
−
</div></div>
 
−
===References===
 
−
# Kennedy BJ. Diethylstilbestrol versus testosterone propionate therapy in advanced breast cancer. Surg Gynecol Obstet. 1965 Jun;120:1246-50. [https://pubmed.ncbi.nlm.nih.gov/14285946 PubMed]
 
−
# Carter AC, Sedransk N, Kelley RM, Ansfield FJ, Ravdin RG, Talley RW, Potter NR; Cooperative Breast Cancer Group. Diethylstilbestrol: recommended dosages for different categories of breast cancer patients: report of the Cooperative Breast Cancer Group. JAMA. 1977 May 9;237(19):2079-8. [https://jamanetwork.com/journals/jama/article-abstract/353009 link to original article] [https://pubmed.ncbi.nlm.nih.gov/576887 PubMed]
 
−
# Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. [https://doi.org/10.1056/NEJM198101013040104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7001242 PubMed]
 
−
# Kiang DT, Frenning DH, Gay J, Goldman AI, Kennedy BJ. Combination therapy of hormone and cytotoxic agents in advanced breast cancer. Cancer. 1981 Feb 1;47(3):452-6. [https://doi.org/10.1002/1097-0142(19810201)47:3%3C452::AID-CNCR2820470305%3E3.0.CO;2-Y link to original article] [https://pubmed.ncbi.nlm.nih.gov/7013960/ PubMed]
 
−
## '''Update:''' Kiang DT, Gay J, Goldman A, Kennedy BJ. A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med. 1985 Nov 14;313(20):1241-6. [https://doi.org/10.1056/NEJM198511143132001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3903501 PubMed]
 
−
==CTCb, then auto HSCT {{#subobject:02f569|Regimen=1}}==
 
−
CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3dea9c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM200004133421501 Stadtmauer et al. 2000]
 
−
|1990-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer#CMF_2|CMF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''No longer used, but of historical interest.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Thiotepa (Thioplex)]]
 
−
*[[Carboplatin (Paraplatin)]]
 
−
</div></div>
 
−
===References===
 
−
# Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. [https://doi.org/10.1056/NEJM200004133421501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10760307 PubMed]
 
−
==Cyclophosphamide monotherapy {{#subobject:78bzec|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9dfaca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025018/ Rubens et al. 1975]
 
−
|1970-1974
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CMFV|CMFV]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
</div></div>
 
−
===References===
 
−
# Rubens RD, Knight RK, Hayward JL. Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination. Br J Cancer. 1975 Dec;32(6):730-6. [https://doi.org/10.1038/bjc.1988.273 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025018/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/766800/ PubMed]
 
−
==Estradiol monotherapy {{#subobject:edd4bd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6 mg/day {{#subobject:8e8202|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ Ellis et al. 2009]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#Estradiol_monotherapy|Estradiol]]; 30 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CBR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Estradiol]] 6 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 30 mg/day {{#subobject:8fahc02|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ Ellis et al. 2009]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Estradiol_monotherapy|Estradiol]]; 6 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CBR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Estradiol]] 30 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA. 2009 Aug 19;302(7):774-80. [https://jamanetwork.com/journals/jama/fullarticle/184425 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19690310/ PubMed] NCT00324259
 
−
==Fluoxymesterone monotherapy {{#subobject:835187|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1914f4|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM195810022591404 Kennedy 1958]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Fluoxymesterone (Halotestin)]]
 
−
</div></div>
 
−
===References===
 
−
# Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med. 1958 Oct 2;259(14):673-5. [https://doi.org/10.1056/NEJM195810022591404 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13590423 PubMed]
 
−
==Formestane monotherapy {{#subobject:6c7bb9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8b5e67|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(84)92795-8 Coombes et al. 1984]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Pilot
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/s0959-8049(97)00105-6 Thürlimann et al. 1997 (SAKK 20/90)]
 
−
|1991-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Megestrol_monotherapy|Megestrol]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Formestane (Lentaron)]]
 
−
</div></div>
 
−
===References===
 
−
# Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237-9. [https://doi.org/10.1016/S0140-6736(84)92795-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6150277 PubMed]
 
−
# '''SAKK 20/90:''' Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research. Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. [https://doi.org/10.1016/s0959-8049(97)00105-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9376181 PubMed]
 
−
==Medroxyprogesterone monotherapy {{#subobject:6c7bb9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 500 mg/day {{#subobject:8b5e67|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://journals.sagepub.com/doi/abs/10.1177/030089167806400204 Cuna et al. 1978]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (E-de-esc)
 
−
|[[#Medroxyprogesterone_monotherapy|MPA]]; 1000 mg/day
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/0014-2964(79)90097-5 Pannuti et al. 1979 (UICC 75-09)]
 
−
|NR
 
−
|style="background-color:#1a9851"|Randomized (C)
 
−
|[[#Medroxyprogesterone_monotherapy|MPA]]; 1500 mg/day
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 Canney et al. 1988]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.9.3141 Byrne et al. 1997 (ANZ8613)]
 
−
|1987-1993
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Medroxyprogesterone_.26_Tamoxifen_99|MPA & Tamoxifen]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
 
−
|-
 
−
|}
 
−
''Note: Canney et al. 1988 does not have dosing information in the abstract.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Medroxyprogesterone (MPA)]] 500 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 900 mg/day {{#subobject:88ge67|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 van Veelen et al. 1986]
 
−
|1980-1984
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Medroxyprogesterone (MPA)]] 300 mg PO three times per day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1000 mg/day (high-dose) {{#subobject:62af61|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1984.2.5.414 Cavalli et al. 1984]
 
−
|1979-1982
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|[[#Medroxyprogesterone_monotherapy|MPA]]; low-dose
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|[https://doi.org/10.1007/BF01961246 Garcia-Giralt et al. 1992]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a058657 Castiglione-Gertsch et al. 1993]
 
−
|1982-1985
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1994.12.8.1630 Muss et al. 1994]
 
−
|1985-1990
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Medroxyprogesterone (MPA)]] 1000 mg PO or IM once per day or 500 mg PO twice per day
 
−
'''Continued indefinitely'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 1200 mg/day (high-dose) {{#subobject:628ga1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(19851201)56:11%3C2576::aid-cncr2820561107%3E3.0.co;2-i Izuo et al. 1985]
 
−
|1981-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Mepitiostate_monotherapy_77|Mepitiostane]]
 
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Medroxyprogesterone (MPA)]] 400 mg PO three times per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Cuna GR, Calciati A, Strada MR, Bumma C, Campio L. High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. Tumori. 1978 Apr 30;64(2):143-9. [https://journals.sagepub.com/doi/abs/10.1177/030089167806400204 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/354147 PubMed]
 
−
# '''UICC 75-09:''' Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, Becchi G, Mattioli G, Barbanti F, Marra GA, Persiani W, Cacciari L, Spagnolo F, Palenzona D, Rocchetta G. Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. Eur J Cancer. 1979 Apr;15(4):593-601. [https://doi.org/10.1016/0014-2964(79)90097-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/86447 PubMed]
 
−
# Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol. 1984 May;2(5):414-9. [https://doi.org/10.1200/JCO.1984.2.5.414 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6233398 PubMed]
 
−
# Izuo M, Yoshida M, Tominaga T, Abe O, Enomoto K, Nomura Y, Kubo K, Takatani O. A phase III trial of oral high-dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer. Cancer. 1985 Dec 1;56(11):2576-9. [https://doi.org/10.1002/1097-0142(19851201)56:11%3C2576::aid-cncr2820561107%3E3.0.co;2-i link to original article] [https://pubmed.ncbi.nlm.nih.gov/2932213 PubMed]
 
−
# van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7-13. [https://doi.org/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2939943 PubMed]
 
−
# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. [https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2970555 PubMed]
 
−
# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. [https://doi.org/10.1007/BF01961246 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8443401 PubMed]
 
−
# Castiglione-Gertsch M, Pampallona S, Varini M, Cavalli F, Brunner K, Senn HJ, Goldhirsch A, Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?. Ann Oncol. 1993 Nov;4(9):735-40. [https://doi.org/10.1093/oxfordjournals.annonc.a058657 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8280653 PubMed]
 
−
# Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, Powell BL, Richards F, Spurr CL, Eagle K, White DR; Piedmont Oncology Association. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study. J Clin Oncol. 1994 Aug;12(8):1630-8. [https://doi.org/10.1200/JCO.1994.12.8.1630 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8040675 PubMed]
 
−
# '''ANZ8613:''' Byrne MJ, Gebski V, Forbes J, Tattersall MH, Simes RJ, Coates AS, Dewar J, Lunn M, Flower C, Gill PG, Stewart J; Australian-New Zealand Breast Cancer Trials Group. Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. J Clin Oncol. 1997 Sep;15(9):3141-8. [https://doi.org/10.1200/JCO.1997.15.9.3141 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9294477 PubMed]
 
−
==Megestrol monotherapy {{#subobject:a806f8|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:27fd99|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.7.1098 Muss et al. 1988]
 
−
|1981-1984
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1007/BF01810736 Lundgren et al. 1989]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a058658 Gill et al. 1993]
 
−
|1984-1989
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]<br>2. [[#Megestrol_.26_Tamoxifen_88|Megestrol & Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1996.14.7.2000 Buzdar et al. 1996]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.7.2494 Russell et al. 1997 (SWOG S8312)]
 
−
|1984-1990
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Aminoglutethimide.2C_Hydrocortisone.2C_Megestrol_99|Aminoglutethimide, Hydrocortisone, Megestrol]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1990.8.11.1797 Muss et al. 1990]
 
−
|1985-1988
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Megestrol_monotherapy|Megestrol]]; higher-dose
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/0959-8049(96)00191-8 Stuart et al. 1996]
 
−
|1985-1988
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.1.64 Abrams et al. 1999 (CALGB 8741)]
 
−
|1987-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Megestrol_monotherapy|Megestrol]]; higher-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W Buzdar et al. 1996 (Protocol 03)]
 
−
|1989-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fadrozole_monotherapy_77|Fadrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W Buzdar et al. 1996 (Protocol 06)]
 
−
|1989-1991
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fadrozole_monotherapy_77|Fadrozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/s0959-8049(97)00105-6 Thürlimann et al. 1997 (SAKK 20/90)]
 
−
|1991-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Formestane_monotherapy|Formestane]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1999.17.1.52 Goss et al. 1999]
 
−
|1991-1995
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Vorozole_monotherapy_77|Vorozole]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[https://doi.org/10.1016/0959-8049(95)00014-3 Jonat et al. 1996]
 
−
|1993-1994
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1200/JCO.1998.16.2.453 Dombernowsky et al. 1998 (AR/BC2)]
 
−
|rowspan=2|1993-1994
 
−
|rowspan=2 style="background-color:#1a9851"|Randomized (C)
 
−
|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2000.18.7.1399 Kaufmann et al. 2000]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer,_ER-positive#Exemestane_monotherapy_3|Exemestane]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.14.3357 Buzdar et al. 2001]
 
−
|NR
 
−
| style="background-color:#1a9851"|Phase 3 (C)
 
−
|1. [[Breast_cancer#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day<br>2. [[Breast_cancer#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for Jonat et al. 1996 & Buzdar et al. 1996 is based on the 1998 pooled update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Megestrol (Megace)]] 160 mg PO once per day or 40 mg PO four times per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
# Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM; Piedmont Oncology Association. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098-106. [https://doi.org/10.1200/JCO.1988.6.7.1098 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3292710/ PubMed]
 
−
# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. [https://doi.org/10.1007/BF01810736 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2690972 PubMed]
 
−
# Muss HB, Case LD, Capizzi RL, Cooper MR, Cruz J, Jackson D, Richards F 2nd, Powell BL, Spurr CL, White D, Zekan P, Read S, Cates-Wilkie S, Bearden J, McCullough J, Callahan R, Karb K, Atkins J, Paschal B, Ramseur B, Lusk J, Stanley V; Piedmont Oncology Association. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1990 Nov;8(11):1797-805. [https://doi.org/10.1200/jco.1990.8.11.1797 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2230868 PubMed]
 
−
# Gill PG, Gebski V, Snyder R, Burns I, Levi J, Byrne M, Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741-4. [https://doi.org/10.1093/oxfordjournals.annonc.a058658 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8280654 PubMed]
 
−
# Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996 Mar;32A(3):404-12. [https://doi.org/10.1016/0959-8049(95)00014-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8814682 PubMed]
 
−
## '''Pooled update:''' Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://doi.org/10.1200/JCO.1996.14.7.2000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8683230/ PubMed]
 
−
## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://doi.org/10.1002/%28SICI)1097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9740079 PubMed]
 
−
#'''Protocol 03:''' Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. [https://doi.org/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W link to original article] [https://pubmed.ncbi.nlm.nih.gov/8640699 PubMed]
 
−
#'''Protocol 06:''' Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. [https://doi.org/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W link to original article] [https://pubmed.ncbi.nlm.nih.gov/8640699 PubMed]
 
−
# Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://doi.org/10.1200/JCO.1996.14.7.2000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8683230/ PubMed]
 
−
## '''Update:''' Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A; Arimidex Study Group. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 Feb 15;79(4):730-9. [https://doi.org/10.1002/%28SICI)1097-0142%2819970215%2979%3A4%3C730%3A%3AAID-CNCR10%3E3.0.CO%3B2-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9024711 PubMed]
 
−
## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://doi.org/10.1002/%28SICI)1097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9740079 PubMed]
 
−
# Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer. 1996 Oct;32A(11):1888-92. [https://doi.org/10.1016/0959-8049(96)00191-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8943670/ PubMed]
 
−
# '''SAKK 20/90:''' Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research. Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. [https://doi.org/10.1016/s0959-8049(97)00105-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9376181 PubMed]
 
−
# '''SWOG S8312:''' Russell CA, Green SJ, O'Sullivan J, Hynes HE, Budd GT, Congdon JE, Martino S, Osborne CK. Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial. J Clin Oncol. 1997 Jul;15(7):2494-501. [https://doi.org/10.1200/JCO.1997.15.7.2494 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9215817 PubMed]
 
−
# '''AR/BC2:''' Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998 Feb;16(2):453-61. [https://doi.org/10.1200/JCO.1998.16.2.453 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9469328 PubMed]
 
−
# Goss PE, Winer EP, Tannock IF, Schwartz LH; North American Vorozole Study Group. Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. J Clin Oncol. 1999 Jan;17(1):52-63. [https://doi.org/10.1200/JCO.1999.17.1.52 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10458218 PubMed]
 
−
# '''CALGB 8741:''' Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, Norton L. Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and Leukemia Group B phase III study 8741. J Clin Oncol. 1999 Jan;17(1):64-73. [https://doi.org/10.1200/jco.1999.17.1.64 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10458219 PubMed]
 
−
# Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G; Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000 Apr;18(7):1399-411. [https://doi.org/10.1200/JCO.2000.18.7.1399 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10735887 PubMed]
 
−
# Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001 Jul 15;19(14):3357-66. [https://doi.org/10.1200/JCO.2001.19.14.3357 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11454883 PubMed]
 
−
==Melphalan monotherapy {{#subobject:b913c5|Regimen=1}}==
 
−
P: '''<u>P</u>'''henylalanine mustard (Melphalan)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ab3663|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H Canellos et al. 1976]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Breast_cancer#CMF_2|CMF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''42-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Canellos GP, Pocock SJ, Taylor SG 3rd, Sears ME, Klaasen DJ, Band PR. Combination chemotherapy for metastatic breast carcinoma: prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976 Nov;38(5):1882-6. [https://doi.org/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H link to original article] [https://pubmed.ncbi.nlm.nih.gov/991103 PubMed]
 
−
==Methotrexate & Thiotepa {{#subobject:c67a88|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4c1582|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/13950199 Greenspan et al. 1963]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''Note: this is possibly the first published trial of combination chemotherapy in breast cancer.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]]
 
−
*[[Thiotepa (Tepadina)]]
 
−
</div></div>
 
−
===References===
 
−
# Greenspan EM, Fieber M, Lesnick G, Edelman S. Response of advanced breast carcinoma to the combination of the antimetabolite, Methotrexate, and the alkylating agent, thio-TEPA. J Mt Sinai Hosp N Y. 1963 May-Jun;30:246-67. [https://pubmed.ncbi.nlm.nih.gov/13950199 PubMed]
 
−
==Mitoxantrone monotherapy {{#subobject:c67f55|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4c8527|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/0140-6736(90)90277-C Harris et al. 1990]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 Cowan et al. 1991 (SWOG S8203)]
 
−
|1983-1986
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Bisantrene_monotherapy_77|Bisantrene]]<br>2. [[Breast_cancer#Doxorubicin_monotherapy_3|Doxorubicin]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Harris AL, Cantwell BM, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RG. Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer. Lancet. 1990 Jan 27;335(8683):186-90. [https://doi.org/10.1016/0140-6736(90)90277-C link to original article] [https://pubmed.ncbi.nlm.nih.gov/1967666 PubMed]
 
−
# '''SWOG S8203:''' Cowan JD, Neidhart J, McClure S, Coltman CA Jr, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CB, Osborne CK. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Aug 7;83(15):1077-84. [https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1875415 PubMed]
 
−
==Mitoxantrone & Vinorelbine (MV) {{#subobject:eb48ba|Regimen=1}}==
 
−
MV: '''<u>M</u>'''itoxantrone & '''<u>V</u>'''inorelbine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:hgaibc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0959-8049(01)00093-4 Namer et al. 2001]
 
−
|NR in abstract
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
 
−
|1a. [[Breast_cancer#FAC_3|FAC]]<br>1b. [[Breast_cancer#FEC_3|FEC]]
 
−
| style="background-color:#eeee01" |Equivalent ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]]
 
−
*[[Vinorelbine (Navelbine)]]
 
−
</div></div>
 
−
===References===
 
−
#Namer M, Soler-Michel P, Turpin F, Chinet-Charrot P, de Gislain C, Pouillart P, Delozier T, Luporsi E, Etienne PL, Schraub S, Eymard JC, Serin D, Ganem G, Calais G, Maillart P, Colin P, Trillet-Lenoir V, Prevost G, Tigaud D, Clavère P, Marti P, Romieu G, Wendling JL. Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer. Eur J Cancer. 2001 Jun;37(9):1132-40. [https://doi.org/10.1016/s0959-8049(01)00093-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11378344/ PubMed]
 
−
==STAMP-I {{#subobject:c08ab4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7gy709|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1988.6.9.1368 Peters et al. 1988]
 
−
|NR
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1038/sj.bmt.1705367 Vredenburgh et al. 2006]
 
−
|1992-1997
 
−
|style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer_-_null_regimens#Observation_2|Observation]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Duke AFM x 2 to 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carmustine (BCNU)]] 600 mg/m<sup>2</sup> IV once on day -3
 
−
*[[Cisplatin (Platinol)]] 55 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day -6 (total dose: 165 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 1875 mg/m<sup>2</sup> IV once per day on days -6 to -4
 
−
'''Stem cells re-infused on days -1, 0, +1'''
 
−
</div></div>
 
−
===References===
 
−
# Peters WP, Shpall EJ, Jones RB, Olsen GA, Bast RC, Gockerman JP, Moore JO. High-dose combination alkylating agents with bone marrow support as initial treatment for metastatic breast cancer. J Clin Oncol. 1988 Sep;6(9):1368-76. [https://doi.org/10.1200/JCO.1988.6.9.1368 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3047332 PubMed]
 
−
# Vredenburgh JJ, Madan B, Coniglio D, Ross M, Broadwater G, Niedzwiecki D, Edwards J, Marks L, Vandemark R, McDonald C, Affronti ML, Peters WP. A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy. Bone Marrow Transplant. 2006 Jun;37(11):1009-15. [https://doi.org/10.1038/sj.bmt.1705367 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16633363 PubMed]
 
−
==TAD (Tamoxifen) {{#subobject:1ac555|Regimen=1}}==
 
−
TAD: '''<u>T</u>'''amoxifen, '''<u>A</u>'''minoglutethimide, '''<u>D</u>'''anazol
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:0b2c27|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(84)91872-5 Powles et al. 1984]
 
−
|1979-1983
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|}
 
−
''Note: this patient population was not selected by hormone receptor status.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Endocrine therapy====
 
−
*[[Tamoxifen (Nolvadex)]]
 
−
*[[Aminoglutethimide (Cytadren)]]
 
−
*[[Danazol (Danocrine)]]
 
−
</div></div>
 
−
===References===
 
−
# Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. Lancet. 1984 Jun 23;1(8391):1369-73. [https://doi.org/10.1016/S0140-6736(84)91872-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6145832 PubMed]
 
−
==Thiotepa monotherapy {{#subobject:123f55|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4a8d27|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM195505262522101 Bateman 1955]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Thiotepa (Thioplex)]]
 
−
</div></div>
 
−
===References===
 
−
# Bateman JC. Chemotherapy of solid tumors with triethylene thiophosphoramide. N Engl J Med. 1955 May 26;252(21):879-87. [https://doi.org/10.1056/NEJM195505262522101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14370446 PubMed]
 
−
==VAP {{#subobject:4b99b8|Regimen=1}}==
 
−
VAP: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin),  '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7d4b85|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Dates of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1987.5.7.1056 Leonard et al. 1987]
 
−
|NR
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Mitoxantrone.2C_Vincristine.2C_Prednisolone_99|VMP]]
 
−
| style="background-color:#1a9850" |Superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Doxorubicin (Adriamycin)]]
 
−
====Endocrine therapy====
 
−
*[[Prednisolone (Millipred)]]
 
−
</div></div>
 
−
===References===
 
−
# Leonard RC, Cornbleet MA, Kaye SB, Soukop M, White G, Hutcheon AW, Robinson S, Kerr ME, Smyth JF. Mitoxantrone versus doxorubicin in combination chemotherapy for advanced carcinoma of the breast. J Clin Oncol. 1987 Jul;5(7):1056-63. [https://doi.org/10.1200/JCO.1987.5.7.1056 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3298559 PubMed]
 
−
[[Category:Breast cancer regimens]]
 
−
[[Category:Historical regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Malignant breast neoplasm]]
 

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