Difference between revisions of "Breast cancer, ER-positive - historical"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
</div> | </div> | ||
− | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only | + | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Breast_cancer,_ER-positive|main ER+ breast cancer page]] for current regimens. |
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
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==ACT {{#subobject:4a01b8|Regimen=1}}== | ==ACT {{#subobject:4a01b8|Regimen=1}}== | ||
ACT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''amoxifen | ACT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''amoxifen | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #1, 40/500/20 {{#subobject:7b46yg|Variant=1}}=== | ===Regimen variant #1, 40/500/20 {{#subobject:7b46yg|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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|1994-1999 | |1994-1999 | ||
|style="background-color:#1a9851" |Phase 3 (E-esc) | |style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|Tamoxifen]] |
| style="background-color:#91cf60" |Seems to have superior RFS | | style="background-color:#91cf60" |Seems to have superior RFS | ||
|- | |- | ||
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**Cycles 1 to 6: 500 mg/m<sup>2</sup> IV once on day 1 | **Cycles 1 to 6: 500 mg/m<sup>2</sup> IV once on day 1 | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Tamoxifen (Nolvadex)]] 20 mg PO once per day | + | *[[Tamoxifen (Nolvadex)]] 20 mg PO once per day on days 1 to 28 |
− | '''28-day cycle for | + | '''28-day cycle for 26 cycles (2 years)''' |
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #2, 60/600/20 {{#subobject:7b4b85|Variant=1}}=== | ===Regimen variant #2, 60/600/20 {{#subobject:7b4b85|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 64: | Line 64: | ||
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | |2. [[Breast_cancer,_ER-positive# | + | |2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|Tamoxifen]] |
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
|- | |- | ||
Line 79: | Line 79: | ||
**Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1 | **Cycles 1 to 4: 600 mg/m<sup>2</sup> IV once on day 1 | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day | + | *[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day on days 1 to 21 |
− | '''21-day cycle for | + | '''21-day cycle for 87 cycles (5 years)''' |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 87: | Line 87: | ||
# '''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] | # '''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] | # '''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] | ||
− | ==Bilateral | + | |
− | <div class="toccolours" style="background-color:# | + | ==Bilateral oophorectomy== |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 100: | Line 101: | ||
|NR | |NR | ||
| style="background-color:#1a9851" |Randomized (C) | | style="background-color:#1a9851" |Randomized (C) | ||
− | |[[#CFP_. | + | |[[#CFP_.26_Bilateral_oophorectomy|CFP & Oophorectomy]] |
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1998.16.3.994 Taylor et al. 1998 (SWOG S8692)] | ||
+ | |1987-08-01 to 1995-07-15 | ||
+ | | style="background-color:#1a9851" |Randomized (C) | ||
+ | |[[#Goserelin_monotherapy_999|Goserelin]] | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether equivalent FFS/OS (co-primary endpoints) | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5052674/ Love et al. 2016 (OSU-0476)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5052674/ Love et al. 2016 (OSU-0476)] | ||
|2004-2011 | |2004-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[ | + | |[[#Mid-luteal_phase_bilateral_oophorectomy_999|Mid-luteal phase oophorectomy]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
Line 116: | Line 123: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[ | + | *[[Bilateral_oophorectomy|Bilateral oophorectomy]] |
</div> | </div> | ||
<div class="toccolours" style="background-color:#cbd5e7"> | <div class="toccolours" style="background-color:#cbd5e7"> | ||
Line 124: | Line 131: | ||
===References=== | ===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] | # 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] | ||
+ | #'''SWOG S8692:''' Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol. 1998 Mar;16(3):994-9. [https://doi.org/10.1200/jco.1998.16.3.994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9508182/ 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] [https://clinicaltrials.gov/study/NCT00293540 NCT00293540] | # '''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] [https://clinicaltrials.gov/study/NCT00293540 NCT00293540] | ||
− | ==CFP & Bilateral | + | |
− | CFP & Bilateral | + | ==CFP & Bilateral oophorectomy {{#subobject:ba429d|Regimen=1}}== |
− | <div class="toccolours" style="background-color:# | + | CFP & Bilateral oophorectomy: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone & Bilateral oophorectomy |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:26519a|Variant=1}}=== | ===Regimen {{#subobject:26519a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 139: | Line 148: | ||
|NR | |NR | ||
| style="background-color:#1a9851" |Randomized (E-esc) | | style="background-color:#1a9851" |Randomized (E-esc) | ||
− | |[[# | + | |[[#Bilateral_oophorectomy|Bilateral oophorectomy]] |
| style="background-color:#91cf60" |Seems to have superior PFS | | style="background-color:#91cf60" |Seems to have superior PFS | ||
|- | |- | ||
Line 153: | Line 162: | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
*[[Prednisone (Sterapred)]] 30 mg PO once per day on days 1 to 7 | *[[Prednisone (Sterapred)]] 30 mg PO once per day on days 1 to 7 | ||
− | *[[ | + | *[[Bilateral_oophorectomy|Bilateral oophorectomy]] |
'''35-day cycles''' | '''35-day cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | # 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] | ||
+ | |||
+ | ==CMFT {{#subobject:acff18|Regimen=1}}== | ||
+ | CMFT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===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/10.1200/JCO.1996.14.10.2731 Pritchard et al. 1996 (NCIC-CTG MA.4)] | ||
+ | |1984-1990 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|Tamoxifen]] | ||
+ | | style="background-color:#ffffbf" |Did not meet 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==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] as follows: | ||
+ | **Cycles 1 to 8: 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Methotrexate (MTX)]] as follows: | ||
+ | **Cycles 1 to 8: 40 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Fluorouracil (5-FU)]] as follows: | ||
+ | **Cycles 1 to 8: 600 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Endocrine therapy==== | ||
+ | *[[Tamoxifen (Nolvadex)]] 30 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycle for 35 cycles (2 years)''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''NCIC-CTG MA.4:''' Pritchard KI, Paterson AH, Paul NA, Zee B, Fine S, Pater J; National Cancer Institute of Canada Clinical Trials Group. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. J Clin Oncol. 1996 Oct;14(10):2731-7. [https://doi.org/10.1200/JCO.1996.14.10.2731 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8874334/ PubMed] | ||
+ | ## '''Update:''' Pritchard KI, Paterson AH, Fine S, Paul NA, Zee B, Shepherd LE, Abu-Zahra H, Ragaz J, Knowling M, Levine MN, Verma S, Perrault D, Walde PL, Bramwell VH, Poljicak M, Boyd N, Warr D, Norris BD, Bowman D, Armitage GR, Weizel H, Buckman RA; NCIC-CTG. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1997 Jun;15(6):2302-11. [https://doi.org/10.1200/JCO.1997.15.6.2302 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9196144/ PubMed] | ||
==PFT {{#subobject:1cb87f|Regimen=1}}== | ==PFT {{#subobject:1cb87f|Regimen=1}}== | ||
PFT: '''<u>P</u>'''henylalanine mustard (Melphalan), 5-'''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen | PFT: '''<u>P</u>'''henylalanine mustard (Melphalan), 5-'''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
− | ===Regimen {{#subobject:c084f5|Variant=1}}=== | + | ===Regimen variant #1, 2 years of tamoxifen {{#subobject:c084f5|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
Line 175: | Line 222: | ||
|[[#PF|PF]] | |[[#PF|PF]] | ||
| style="background-color:#1a9850" |Superior RFS | | style="background-color:#1a9850" |Superior RFS | ||
+ | |- | ||
+ | |} | ||
+ | <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)]] 4 mg/m<sup>2</sup> PO 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==== | ||
+ | *[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day on days 1 to 42 | ||
+ | '''42-day cycle for 17 cycles (2 years)''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #2, 5 years of tamoxifen {{#subobject:c0hgc3|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|[https://doi.org/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)] | ||
Line 182: | Line 251: | ||
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | |2. [[Breast_cancer,_ER-positive# | + | |2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|Tamoxifen]] |
| style="background-color:#91cf60" |Seems to have superior DDFS | | style="background-color:#91cf60" |Seems to have superior DDFS | ||
|- | |- | ||
Line 192: | Line 261: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Melphalan (Alkeran)]] | + | *[[Melphalan (Alkeran)]] as follows: |
− | *[[Fluorouracil (5-FU)]] | + | **Cycles 1 to 17: 4 mg/m<sup>2</sup> PO once per day on days 1 to 5 |
+ | *[[Fluorouracil (5-FU)]] as follows: | ||
+ | **Cycles 1 to 17: 300 mg/m<sup>2</sup> IV once per day on days 1 to 5 | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Tamoxifen (Nolvadex)]] | + | *[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day on days 1 to 42 |
+ | '''42-day cycle for 43 cycles (5 years)''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | + | # '''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] '''contains dosing details in manuscript''' [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, 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] | ## '''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] | + | # '''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] | ## '''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 {{#subobject:c08464|Regimen=1}}== | ||
PT: '''<u>P</u>'''rednisone & '''<u>T</u>'''amoxifen | PT: '''<u>P</u>'''rednisone & '''<u>T</u>'''amoxifen | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:2fc709|Variant=1}}=== | ===Regimen {{#subobject:2fc709|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 236: | Line 309: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Prednisone (Sterapred)]] | + | *[[Prednisone (Sterapred)]] 7.5 mg PO once per day on days 1 to 28 |
− | *[[Tamoxifen (Nolvadex)]] | + | *[[Tamoxifen (Nolvadex)]] 20 mg PO once per day on days 1 to 28 |
+ | '''28-day cycle for 13 cycles (12 months)''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | + | # '''LBCS III:''' 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6144974/ PubMed] |
+ | # '''LBCS 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6144974/ PubMed] | ||
=Metastatic disease, all lines of therapy= | =Metastatic disease, all lines of therapy= | ||
==Aminoglutethimide monotherapy {{#subobject:821a2c|Regimen=1}}== | ==Aminoglutethimide monotherapy {{#subobject:821a2c|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:f62b32|Variant=1}}=== | ===Regimen {{#subobject:f62b32|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 262: | Line 337: | ||
|NR | |NR | ||
| style="background-color:#1a9851" |Randomized (E-switch-ic) | | style="background-color:#1a9851" |Randomized (E-switch-ic) | ||
− | |[[ | + | |[[#Bilateral_adrenalectomy_888|Bilateral adrenalectomy]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 271: | Line 346: | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/80.14.1147 Canney et al. 1988] |
|NR | |NR | ||
|style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
Line 291: | Line 366: | ||
|[https://pubmed.ncbi.nlm.nih.gov/8135469 Robustelli della Cuna et al. 1993] | |[https://pubmed.ncbi.nlm.nih.gov/8135469 Robustelli della Cuna et al. 1993] | ||
|NR | |NR | ||
− | | style="background-color:#1a9851" |Phase 3 ( | + | | style="background-color:#1a9851" |Phase 3 (E-de-esc) |
|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]; higher-dose | |[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]; higher-dose | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
Line 298: | Line 373: | ||
|1977-NR | |1977-NR | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |1. [[Breast_cancer,_ER-positive# | + | |1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]]<br>2. [[#Bilateral_adrenalectomy_888|Bilateral adrenalectomy]] |
| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DOR/TTF/OS | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DOR/TTF/OS | ||
+ | |- | ||
+ | |rowspan=2|[https://doi.org/10.1023/a:1008226721932 Gershanovich et al. 1998 (AR/BC3)] | ||
+ | |rowspan=2|NR | ||
+ | |rowspan=2 style="background-color:#1a9851"|Randomized (C) | ||
+ | |1. [[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
+ | |- | ||
+ | |2. [[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day | ||
+ | | style="background-color:#fee08b" |Might have inferior ORR | ||
|- | |- | ||
|} | |} | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Aminoglutethimide (Cytadren)]] | + | *[[Aminoglutethimide (Cytadren)]] 250 mg PO twice per day |
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *[[Hydrocortisone (Cortef)]] | + | *[[Hydrocortisone (Cortef)]] 37.5 mg/day PO |
+ | '''Continued indefinitely''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 312: | Line 397: | ||
# 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] | # 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] | # 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:// | + | # 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://doi.org/10.1093/jnci/80.14.1147 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] | # 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] | # 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] | + | # 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. '''contains dosing details in abstract''' [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] | # 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] | ||
− | ==Bilateral | + | # '''AR/BC3:''' Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M, Buzzi F, Bodrogi I, Ludwig H, Reichardt P, O'Higgins N, Romieu G, Friederich P, Lassus M; Letrozole International Trial Group. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol. 1998 Jun;9(6):639-45. [https://doi.org/10.1023/a:1008226721932 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9681078/ PubMed] |
− | <div class="toccolours" style="background-color:# | + | |
+ | ==Bilateral oophorectomy {{#subobject:dh71bb|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:4979xq|Variant=1}}=== | ===Regimen {{#subobject:4979xq|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 330: | Line 417: | ||
|1978-1984 | |1978-1984 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]] |
| style="background-color:#ffffbf" |Did not meet endpoints | | style="background-color:#ffffbf" |Did not meet endpoints | ||
|- | |- | ||
Line 336: | Line 423: | ||
|1979-1983 | |1979-1983 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]] |
| style="background-color:#fee08b" |Might have inferior PFS | | style="background-color:#fee08b" |Might have inferior PFS | ||
|- | |- | ||
Line 342: | Line 429: | ||
|NR | |NR | ||
|style="background-color:#1a9851" |Randomized (C) | |style="background-color:#1a9851" |Randomized (C) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_4|Tamoxifen]] |
| style="background-color:#ffffbf" |Did not meet pooled endpoint of ORR | | style="background-color:#ffffbf" |Did not meet pooled endpoint of ORR | ||
|- | |- | ||
Line 349: | Line 436: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[ | + | *[[Bilateral_oophorectomy|Bilateral oophorectomy]] |
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 358: | Line 445: | ||
==CAF & MPA {{#subobject:6c7ff9|Regimen=1}}== | ==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 | 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:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:b2ce67|Variant=1}}=== | ===Regimen {{#subobject:b2ce67|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 376: | Line 463: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cyclophosphamide (Cytoxan)]] | + | *[[Cyclophosphamide (Cytoxan)]] 100 mg PO once per day on days 1 to 14 |
− | *[[Doxorubicin (Adriamycin)]] | + | *[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
− | *[[Fluorouracil (5-FU)]] | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8 |
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Medroxyprogesterone acetate (MPA)]] | + | *[[Medroxyprogesterone acetate (MPA)]] 1200 mg PO once per day on days 1 to 28 |
+ | '''28-day cycle for 3 cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===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 | + | # 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 manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7946592/ PubMed] |
==DES monotherapy {{#subobject:0a1860|Regimen=1}}== | ==DES monotherapy {{#subobject:0a1860|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:128a40|Variant=1}}=== | ===Regimen {{#subobject:128a40|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 401: | Line 489: | ||
| style="background-color:#d3d3d3" |Not available | | style="background-color:#d3d3d3" |Not available | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1001/jama.1977.03270460065023 Carter et al. 1977] |
|NR | |NR | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
Line 416: | Line 504: | ||
|1977-1980 | |1977-1980 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 423: | Line 511: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Diethylstilbestrol (DES)]] | + | *[[Diethylstilbestrol (DES)]] 5 mg PO three times per day |
+ | '''Continued indefinitely''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | # 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:// | + | # 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://doi.org/10.1001/jama.1977.03270460065023 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] | # 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] | + | # 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] '''contains dosing details in manuscript''' [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] | ## '''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] | ||
+ | |||
==Estradiol monotherapy {{#subobject:edd4bd|Regimen=1}}== | ==Estradiol monotherapy {{#subobject:edd4bd|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #1, 6 mg/day {{#subobject:8e8202|Variant=1}}=== | ===Regimen variant #1, 6 mg/day {{#subobject:8e8202|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 453: | Line 543: | ||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #2, 30 mg/day {{#subobject:8fahc02|Variant=1}}=== | ===Regimen variant #2, 30 mg/day {{#subobject:8fahc02|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 475: | Line 565: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # '''WU 04-0412:''' 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:// | + | # '''WU 04-0412:''' 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://doi.org/10.1001/jama.2009.1204 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] [https://clinicaltrials.gov/study/NCT00324259 NCT00324259] |
==Fluoxymesterone monotherapy {{#subobject:835187|Regimen=1}}== | ==Fluoxymesterone monotherapy {{#subobject:835187|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:1914f4|Variant=1}}=== | ===Regimen {{#subobject:1914f4|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1056/NEJM195810022591404 Kennedy 1958] | |[https://doi.org/10.1056/NEJM195810022591404 Kennedy 1958] | ||
+ | |NR | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
Line 489: | Line 581: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Fluoxymesterone (Halotestin)]] | + | *[[Fluoxymesterone (Halotestin)]] 20 or 40 mg PO once per day |
+ | '''Continued indefinitely''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | + | # 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/13590423/ PubMed] |
==Fluoxymesterone & Tamoxifen {{#subobject:8ujg87|Regimen=1}}== | ==Fluoxymesterone & Tamoxifen {{#subobject:8ujg87|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:ahf4f4|Variant=1}}=== | ===Regimen {{#subobject:ahf4f4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 507: | Line 600: | ||
|1981-1985 | |1981-1985 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#91cf60" |Seems to have superior TTP<sup>1</sup> | | style="background-color:#91cf60" |Seems to have superior TTP<sup>1</sup> | ||
|- | |- | ||
Line 514: | Line 607: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Fluoxymesterone (Halotestin)]] | + | *[[Fluoxymesterone (Halotestin)]] 10 mg PO twice per day |
− | *[[Tamoxifen (Nolvadex)]] | + | *[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day |
+ | '''Continued indefinitely''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
Line 522: | Line 616: | ||
==Formestane monotherapy {{#subobject:6c7bb9|Regimen=1}}== | ==Formestane monotherapy {{#subobject:6c7bb9|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:8b5e67|Variant=1}}=== | ===Regimen {{#subobject:8b5e67|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 546: | Line 640: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Formestane (Lentaron)]] | + | *[[Formestane (Lentaron)]] 250 mg IM once on day 1 |
+ | '''14-day cycles''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | # 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] | + | # '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9376181/ PubMed] |
+ | |||
==Medroxyprogesterone acetate monotherapy {{#subobject:6c7bb9|Regimen=1}}== | ==Medroxyprogesterone acetate monotherapy {{#subobject:6c7bb9|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #1, 500 mg/day {{#subobject:8b5e67|Variant=1}}=== | ===Regimen variant #1, 500 mg/day {{#subobject:8b5e67|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 561: | Line 657: | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1177/030089167806400204 Cuna et al. 1978] |
|NR | |NR | ||
|style="background-color:#1a9851"|Phase 3 (E-de-esc) | |style="background-color:#1a9851"|Phase 3 (E-de-esc) | ||
Line 573: | Line 669: | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/80.14.1147 Canney et al. 1988] |
|NR | |NR | ||
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
Line 592: | Line 688: | ||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #2, 900 mg/day {{#subobject:88ge67|Variant=1}}=== | ===Regimen variant #2, 900 mg/day {{#subobject:88ge67|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 604: | Line 700: | ||
|1980-1984 | |1980-1984 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 613: | Line 709: | ||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #3, 1000 mg/day (high-dose) {{#subobject:62af61|Variant=1}}=== | ===Regimen variant #3, 1000 mg/day (high-dose) {{#subobject:62af61|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 637: | Line 733: | ||
|1982-1985 | |1982-1985 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#d9ef8b" |Might have superior TTP | | style="background-color:#d9ef8b" |Might have superior TTP | ||
|- | |- | ||
Line 643: | Line 739: | ||
|1985-1990 | |1985-1990 | ||
|style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#d9ef8b" |Might have superior OS | | style="background-color:#d9ef8b" |Might have superior OS | ||
|- | |- | ||
Line 652: | Line 748: | ||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #4, 1200 mg/day (high-dose) {{#subobject:628ga1|Variant=1}}=== | ===Regimen variant #4, 1200 mg/day (high-dose) {{#subobject:628ga1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 664: | Line 760: | ||
|1981-1983 | |1981-1983 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |[[# | + | |[[#Mepitiostate_monotherapy_999|Mepitiostane]] |
|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | |style="background-color:#ffffbf"|Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 674: | Line 770: | ||
</div></div> | </div></div> | ||
===References=== | ===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:// | + | # 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://doi.org/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] | # '''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] | # 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] | # 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] | # 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:// | + | # 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://doi.org/10.1093/jnci/80.14.1147 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] | # 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] | # 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] | ||
Line 685: | Line 781: | ||
# '''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] | # '''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}}== | ==Megestrol monotherapy {{#subobject:a806f8|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:27fd99|Variant=1}}=== | ===Regimen {{#subobject:27fd99|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 697: | Line 793: | ||
|1981-1984 | |1981-1984 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 709: | Line 805: | ||
|1984-1989 | |1984-1989 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |1. [[Breast_cancer,_ER-positive# | + | |1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]]<br>2. [[#Megestrol_.26_Tamoxifen_888|Megestrol & Tamoxifen]] |
| style="background-color:#ffffbf" |Did not meet endpoint of ORR | | style="background-color:#ffffbf" |Did not meet endpoint of ORR | ||
|- | |- | ||
Line 733: | Line 829: | ||
|1985-1988 | |1985-1988 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#ffffbf" |Did not meet endpoint of OS | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
|- | |- | ||
Line 745: | Line 841: | ||
|1989-1991 | |1989-1991 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Fadrozole_monotherapy_999|Fadrozole]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 751: | Line 847: | ||
|1989-1991 | |1989-1991 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Fadrozole_monotherapy_999|Fadrozole]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
Line 763: | Line 859: | ||
|1991-1995 | |1991-1995 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Vorozole_monotherapy_999|Vorozole]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | 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] | + | |rowspan=2|[https://doi.org/10.1016/0959-8049(95)00014-3 Jonat et al. 1996] |
− | |1993-1994 | + | |rowspan=2|1993-03 to 1994-09 |
− | | style="background-color:#1a9851" |Phase 3 (C) | + | |rowspan=2 style="background-color:#1a9851" |Phase 3 (C) |
− | |[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]] | + | |1. [[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]; 1 mg/day |
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | ||
+ | |- | ||
+ | |2. [[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]; 10 mg/day | ||
+ | | style="background-color:#ffffbf" |Did not meet endpoint of OS | ||
|- | |- | ||
|rowspan=2|[https://doi.org/10.1200/JCO.1998.16.2.453 Dombernowsky et al. 1998 (AR/BC2)] | |rowspan=2|[https://doi.org/10.1200/JCO.1998.16.2.453 Dombernowsky et al. 1998 (AR/BC2)] | ||
− | |rowspan=2|1993-1994 | + | |rowspan=2|1993-03 to 1994-09 |
|rowspan=2 style="background-color:#1a9851"|Randomized (C) | |rowspan=2 style="background-color:#1a9851"|Randomized (C) | ||
|1. [[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day | |1. [[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day | ||
Line 785: | Line 884: | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[Breast_cancer,_ER-positive#Exemestane_monotherapy_3|Exemestane]] | |[[Breast_cancer,_ER-positive#Exemestane_monotherapy_3|Exemestane]] | ||
− | | style="background-color:#ffffbf" | | + | | style="background-color:#ffffbf" |Inconclusive whether equivalent ORR (primary endpoint)<br><br>Seems to have inferior OS |
|- | |- | ||
|[https://doi.org/10.1200/JCO.2001.19.14.3357 Buzdar et al. 2001] | |[https://doi.org/10.1200/JCO.2001.19.14.3357 Buzdar et al. 2001] | ||
Line 819: | Line 918: | ||
# 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] | # 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] | # '''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 | + | # 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 manuscript''' [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] | # 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] | ||
==TAD (Tamoxifen) {{#subobject:1ac555|Regimen=1}}== | ==TAD (Tamoxifen) {{#subobject:1ac555|Regimen=1}}== | ||
TAD: '''<u>T</u>'''amoxifen, '''<u>A</u>'''minoglutethimide, '''<u>D</u>'''anazol | TAD: '''<u>T</u>'''amoxifen, '''<u>A</u>'''minoglutethimide, '''<u>D</u>'''anazol | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:0b2c27|Variant=1}}=== | ===Regimen {{#subobject:0b2c27|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 836: | Line 935: | ||
|1979-1983 | |1979-1983 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_5|Tamoxifen]] |
| style="background-color:#91cf60" |Seems to have superior ORR | | style="background-color:#91cf60" |Seems to have superior ORR | ||
|- | |- | ||
Line 843: | Line 942: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Tamoxifen (Nolvadex)]] | + | *[[Tamoxifen (Nolvadex)]] 10 mg PO twice per day |
− | *[[Aminoglutethimide (Cytadren)]] | + | *[[Aminoglutethimide (Cytadren)]] 250 mg PO three times per day |
− | *[[Danazol (Danocrine)]] | + | *[[Danazol (Danocrine)]] 100 mg PO three times per day |
+ | ====Supportive therapy==== | ||
+ | *[[Hydrocortisone (Cortef)]] 20 mg PO twice per day | ||
+ | '''Continued indefinitely''' | ||
</div></div> | </div></div> | ||
===References=== | ===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] | + | # 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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6145832/ PubMed] |
+ | |||
=Metastatic disease, subsequent lines of therapy= | =Metastatic disease, subsequent lines of therapy= | ||
==Fluoxymesterone & Tamoxifen {{#subobject:8ujg87|Regimen=1}}== | ==Fluoxymesterone & Tamoxifen {{#subobject:8ujg87|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:ahf4f4|Variant=1}}=== | ===Regimen {{#subobject:ahf4f4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 863: | Line 966: | ||
|NR | |NR | ||
| style="background-color:#1a9851" |Randomized (E-esc) | | style="background-color:#1a9851" |Randomized (E-esc) | ||
− | |[[Breast_cancer,_ER-positive# | + | |[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_6|Tamoxifen]] |
| style="background-color:#1a9850" |Superior TTTF | | style="background-color:#1a9850" |Superior TTTF | ||
|- | |- | ||
Line 869: | Line 972: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Endocrine therapy==== | ====Endocrine therapy==== | ||
− | *[[Fluoxymesterone (Halotestin)]] | + | *[[Fluoxymesterone (Halotestin)]] 7 mg/m<sup>2</sup> PO twice per day |
− | *[[Tamoxifen (Nolvadex)]] | + | *[[Tamoxifen (Nolvadex)]] across a range of doses |
+ | '''Continued indefinitely''' | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | # Tormey DC, Lippman ME, Edwards BK, Cassidy JG. Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. Ann Intern Med. 1983 Feb;98(2):139-44. [https://doi.org/10.7326/0003-4819-98-2-139 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6824247/ PubMed] | + | # Tormey DC, Lippman ME, Edwards BK, Cassidy JG. Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. Ann Intern Med. 1983 Feb;98(2):139-44. [https://doi.org/10.7326/0003-4819-98-2-139 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6824247/ PubMed] |
[[Category:Breast cancer regimens]] | [[Category:Breast cancer regimens]] | ||
[[Category:Historical regimens]] | [[Category:Historical regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Malignant breast neoplasm]] | [[Category:Malignant breast neoplasm]] |
Latest revision as of 11:39, 3 July 2024
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main ER+ breast cancer page for current regimens.
15 regimens on this page
20 variants on this page
|
Adjuvant therapy
ACT
ACT: Adriamycin (Doxorubicin), Cyclophosphamide, Tamoxifen
Regimen variant #1, 40/500/20
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shien et al. 2014 (JCOG9401) | 1994-1999 | Phase 3 (E-esc) | Tamoxifen | Seems to have superior RFS |
Shien et al. 2014 (JCOG9404) | 1994-1999 | Phase 3 (E-de-esc) | TUFT | Did not meet primary endpoint of OS |
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 6: 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 6: 500 mg/m2 IV once on day 1
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 28
28-day cycle for 26 cycles (2 years)
Regimen variant #2, 60/600/20
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1990 (NSABP B-16) | 1985-1988 | Phase 3 (E-esc) | 1. PFT | Not reported |
2. Tamoxifen | Seems to have superior OS |
Preceding treatment
Chemotherapy
- Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 4: 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 4: 600 mg/m2 IV once on day 1
Endocrine therapy
- Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 21
21-day cycle for 87 cycles (5 years)
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. link to original article contains dosing details in manuscript 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. link to original article 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. link to original article contains dosing details in manuscript 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. link to original article link to PMC article contains dosing details in manuscript PubMed
Bilateral oophorectomy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ahmann et al. 1977 | NR | Randomized (C) | CFP & Oophorectomy | Seems to have inferior PFS |
Taylor et al. 1998 (SWOG S8692) | 1987-08-01 to 1995-07-15 | Randomized (C) | Goserelin | Inconclusive whether equivalent FFS/OS (co-primary endpoints) |
Love et al. 2016 (OSU-0476) | 2004-2011 | Phase 3 (C) | Mid-luteal phase oophorectomy | Did not meet primary endpoint of OS |
Preceding treatment
Endocrine therapy
Subsequent treatment
- OSU-0476: Adjuvant tamoxifen
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. link to original article PubMed
- SWOG S8692: Taylor CW, Green S, Dalton WS, Martino S, Rector D, Ingle JN, Robert NJ, Budd GT, Paradelo JC, Natale RB, Bearden JD, Mailliard JA, Osborne CK. Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study. J Clin Oncol. 1998 Mar;16(3):994-9. link to original article 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. link to original article link to PMC article PubMed NCT00293540
CFP & Bilateral oophorectomy
CFP & Bilateral oophorectomy: Cyclophosphamide, Fluorouracil, Prednisone & Bilateral oophorectomy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ahmann et al. 1977 | NR | Randomized (E-esc) | Bilateral oophorectomy | Seems to have superior PFS |
Preceding treatment
- Surgery, 3 weeks prior
Chemotherapy
- Cyclophosphamide (Cytoxan) 150 mg/m2 IV once per day on days 1 to 5
- Fluorouracil (5-FU) 300 mg/m2 IV once per day on days 1 to 5
Endocrine therapy
- Prednisone (Sterapred) 30 mg PO once per day on days 1 to 7
- Bilateral oophorectomy
35-day cycles
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. link to original article contains dosing details in manuscript PubMed
CMFT
CMFT: Cyclophosphamide, Methotrexate, Fluorouracil, Tamoxifen
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pritchard et al. 1996 (NCIC-CTG MA.4) | 1984-1990 | Phase 3 (C) | Tamoxifen | Did not meet endpoint of OS |
Preceding treatment
Chemotherapy
- Cyclophosphamide (Cytoxan) as follows:
- Cycles 1 to 8: 600 mg/m2 IV once on day 1
- Methotrexate (MTX) as follows:
- Cycles 1 to 8: 40 mg/m2 IV once on day 1
- Fluorouracil (5-FU) as follows:
- Cycles 1 to 8: 600 mg/m2 IV once on day 1
Endocrine therapy
- Tamoxifen (Nolvadex) 30 mg PO once per day on days 1 to 21
21-day cycle for 35 cycles (2 years)
References
- NCIC-CTG MA.4: Pritchard KI, Paterson AH, Paul NA, Zee B, Fine S, Pater J; National Cancer Institute of Canada Clinical Trials Group. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. J Clin Oncol. 1996 Oct;14(10):2731-7. link to original article contains dosing details in manuscript PubMed
- Update: Pritchard KI, Paterson AH, Fine S, Paul NA, Zee B, Shepherd LE, Abu-Zahra H, Ragaz J, Knowling M, Levine MN, Verma S, Perrault D, Walde PL, Bramwell VH, Poljicak M, Boyd N, Warr D, Norris BD, Bowman D, Armitage GR, Weizel H, Buckman RA; NCIC-CTG. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1997 Jun;15(6):2302-11. link to original article PubMed
PFT
PFT: Phenylalanine mustard (Melphalan), 5-Fluorouracil, Tamoxifen
Regimen variant #1, 2 years of tamoxifen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1981 (NSABP B-09) | 1977-1980 | Phase 3 (E-RT-esc) | PF | Superior RFS |
Preceding treatment
Chemotherapy
- Melphalan (Alkeran) 4 mg/m2 PO once per day on days 1 to 5
- Fluorouracil (5-FU) 300 mg/m2 IV once per day on days 1 to 5
Endocrine therapy
- Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 42
42-day cycle for 17 cycles (2 years)
Regimen variant #2, 5 years of tamoxifen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1990 (NSABP B-16) | 1985-1988 | Phase 3 (E-esc) | 1. ACT | Not reported |
2. Tamoxifen | Seems to have superior DDFS |
Preceding treatment
Chemotherapy
- Melphalan (Alkeran) as follows:
- Cycles 1 to 17: 4 mg/m2 PO once per day on days 1 to 5
- Fluorouracil (5-FU) as follows:
- Cycles 1 to 17: 300 mg/m2 IV once per day on days 1 to 5
Endocrine therapy
- Tamoxifen (Nolvadex) 10 mg PO twice per day on days 1 to 42
42-day cycle for 43 cycles (5 years)
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. link to original article contains dosing details in manuscript 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. link to original article 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. link to original article 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. link to original article contains dosing details in manuscript 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. link to original article PubMed
PT
PT: Prednisone & Tamoxifen
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Goldhirsch et al. 1984 (LBCS III) | 1978-1981 | Phase 3 (E-esc) | 1. CMFPT | Seems to have inferior DFS |
2. Observation | Superior DFS | |||
Goldhirsch et al. 1984 (LBCS IV) | 1978-1981 | Phase 3 (E-esc) | Observation | Seems to have superior DFS |
Preceding treatment
Endocrine therapy
- Prednisone (Sterapred) 7.5 mg PO once per day on days 1 to 28
- Tamoxifen (Nolvadex) 20 mg PO once per day on days 1 to 28
28-day cycle for 13 cycles (12 months)
References
- LBCS III: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article contains dosing details in manuscript PubMed
- LBCS IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article contains dosing details in manuscript PubMed
Metastatic disease, all lines of therapy
Aminoglutethimide monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Smith et al. 1978 | 1977-1978 | Non-randomized | ||
Santen et al. 1981 | NR | Randomized (E-switch-ic) | Bilateral adrenalectomy | Did not meet primary endpoint of ORR |
Stuart-Harris et al. 1984 | NR | Phase 2 | ||
Canney et al. 1988 | NR | Phase 3 (E-switch-ic) | MPA | Did not meet primary endpoint of ORR |
Lundgren et al. 1989 | NR | Phase 3 (E-switch-ic) | Megestrol | Did not meet primary endpoint of ORR |
Garcia-Giralt et al. 1992 | NR | Phase 3 (E-switch-ic) | MPA | Seems to have superior TTP |
Robustelli della Cuna et al. 1993 | NR | Phase 3 (E-de-esc) | Aminoglutethimide; higher-dose | Did not meet primary endpoint of ORR |
Gale et al. 1994 | 1977-NR | Phase 3 (E-switch-ic) | 1. Tamoxifen 2. Bilateral adrenalectomy |
Did not meet co-primary endpoints of DOR/TTF/OS |
Gershanovich et al. 1998 (AR/BC3) | NR | Randomized (C) | 1. Letrozole; 0.5 mg/day | Did not meet primary endpoint of ORR |
2. Letrozole; 2.5 mg/day | Might have inferior ORR |
Endocrine therapy
- Aminoglutethimide (Cytadren) 250 mg PO twice per day
Supportive therapy
- Hydrocortisone (Cortef) 37.5 mg/day PO
Continued indefinitely
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. link to original article 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. link to original article 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. link to original article 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. link to original article 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. link to original article 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. link to original article 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. contains dosing details in abstract PubMed
- Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ; 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. link to original article PubMed
- AR/BC3: Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M, Buzzi F, Bodrogi I, Ludwig H, Reichardt P, O'Higgins N, Romieu G, Friederich P, Lassus M; Letrozole International Trial Group. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5 mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Ann Oncol. 1998 Jun;9(6):639-45. link to original article contains dosing details in manuscript PubMed
Bilateral oophorectomy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ingle et al. 1986a | 1978-1984 | Phase 3 (C) | Tamoxifen | Did not meet endpoints |
Buchanan et al. 1986 | 1979-1983 | Phase 3 (C) | Tamoxifen | Might have inferior PFS |
Crump et al. 1997 | NR | Randomized (C) | Tamoxifen | Did not meet pooled endpoint of ORR |
Note: while Crump et al. 1997 is a meta-analysis, it is also the primary report for a randomized trial used to support registration of this drug.
Endocrine therapy
References
- Ingle JN, Krook JE, Green SJ, Kubista TP, Everson LK, Ahmann DL, Chang MN, Bisel HF, Windschitl HE, Twito DI, Pfeifle DM. Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer. J Clin Oncol. 1986 Feb;4(2):178-85. link to original article contains dosing details in abstract PubMed
- Buchanan RB, Blamey RW, Durrant KR, Howell A, Paterson AG, Preece PE, Smith DC, Williams CJ, Wilson RG. A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer. J Clin Oncol. 1986 Sep;4(9):1326-30. link to original article contains dosing details in manuscript PubMed
- Crump M, Sawka CA, DeBoer G, Buchanan RB, Ingle JN, Forbes J, Meakin JW, Shelley W, Pritchard KI. An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer. Breast Cancer Res Treat. 1997 Jul;44(3):201-10. link to original article PubMed
CAF & MPA
CAF & MPA: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil, MedroxyProgesterone Acetate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tominaga et al. 1994 | NR | Phase 3 (E-esc) | CAF | Seems to have superior ORR |
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 14
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
Endocrine therapy
- Medroxyprogesterone acetate (MPA) 1200 mg PO once per day on days 1 to 28
28-day cycle for 3 cycles
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. link to original article contains dosing details in manuscript PubMed
DES monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kennedy 1965 | NR in abstract | Randomized (E-switch-ic) | Testosterone | Not available |
Carter et al. 1977 | NR | Phase 3 (E-switch-ic) | DES; other dosings | See paper |
Kiang et al. 1981 | 1975-1982 | Randomized (C) | Cyclophosphamide, 5-FU, DES | Seems to have inferior OS1 |
Ingle et al. 1981 | 1977-1980 | Phase 3 (C) | Tamoxifen | Did not meet primary endpoint of ORR |
1Reported efficacy for Kiang et al. 1981 is based on the 1985 update.
References
- Kennedy BJ. Diethylstilbestrol versus testosterone propionate therapy in advanced breast cancer. Surg Gynecol Obstet. 1965 Jun;120:1246-50. 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. link to original article 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. link to original article 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. link to original article contains dosing details in manuscript 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. link to original article PubMed
Estradiol monotherapy
Regimen variant #1, 6 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ellis et al. 2009 (WU 04-0412) | 2004-2008 | Randomized Phase 2 (E-de-esc) | Estradiol; 30 mg/day | Did not meet primary endpoint of CBR |
Regimen variant #2, 30 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ellis et al. 2009 (WU 04-0412) | 2004-2008 | Randomized Phase 2 (C) | Estradiol; 6 mg/day | Did not meet primary endpoint of CBR |
References
- WU 04-0412: 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. link to original article link to PMC article contains dosing details in abstract PubMed NCT00324259
Fluoxymesterone monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kennedy 1958 | NR | Non-randomized |
References
- Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med. 1958 Oct 2;259(14):673-5. link to original article contains dosing details in manuscript PubMed
Fluoxymesterone & Tamoxifen
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ingle et al. 1988 | 1981-1985 | Phase 3 (E-esc) | Tamoxifen | Seems to have superior TTP1 |
1Reported efficacy is based on the 1991 update.
Endocrine therapy
- Fluoxymesterone (Halotestin) 10 mg PO twice per day
- Tamoxifen (Nolvadex) 10 mg PO twice per day
Continued indefinitely
References
- Ingle JN, Twito DI, Schaid DJ, Cullinan SA, Krook JE, Mailliard JA, Marschke RF, Long HJ, Gerstner JG, Windschitl HE, Everson LK, Pfeifle DM. Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer. J Clin Oncol. 1988 May;6(5):825-31. link to original article contains dosing details in abstract PubMed
- Update: Ingle JN, Twito DI, Schaid DJ, Cullinan SA, Krook JE, Mailliard JA, Tschetter LK, Long HJ, Gerstner JG, Windschitl HE, Levitt R, Pfeifle DM. Combination hormonal therapy with tamoxifen plus fluoxymesterone versus tamoxifen alone in postmenopausal women with metastatic breast cancer: an updated analysis. Cancer. 1991 Feb 15;67(4):886-91. link to original article PubMed
Formestane monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coombes et al. 1984 | NR | Pilot | ||
Thürlimann et al. 1997 (SAKK 20/90) | 1991-1995 | Phase 3 (E-switch-ic) | Megestrol | Did not meet primary endpoint of TTF |
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. link to original article 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. link to original article contains dosing details in manuscript PubMed
Medroxyprogesterone acetate monotherapy
Regimen variant #1, 500 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cuna et al. 1978 | NR | Phase 3 (E-de-esc) | MPA; 1000 mg/day | Did not meet primary endpoint of ORR |
Pannuti et al. 1979 (UICC 75-09) | NR | Randomized (C) | MPA; 1500 mg/day | Did not meet primary endpoint of ORR |
Canney et al. 1988 | NR | Phase 3 (C) | Aminoglutethimide | Did not meet primary endpoint of ORR |
Byrne et al. 1997 (ANZ8613) | 1987-1993 | Phase 3 (C) | MPA & Tamoxifen | Did not meet primary endpoint of TTP |
Note: Canney et al. 1988 does not have dosing information in the abstract.
Regimen variant #2, 900 mg/day
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
van Veelen et al. 1986 | 1980-1984 | Phase 3 (E-switch-ic) | Tamoxifen | Did not meet primary endpoint of ORR |
Endocrine therapy
- Medroxyprogesterone acetate (MPA) 300 mg PO three times per day
Continued indefinitely
Regimen variant #3, 1000 mg/day (high-dose)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cavalli et al. 1984 | 1979-1982 | Phase 3 (E-esc) | MPA; low-dose | Superior ORR |
Garcia-Giralt et al. 1992 | NR | Phase 3 (C) | Aminoglutethimide | Seems to have inferior TTP |
Castiglione-Gertsch et al. 1993 | 1982-1985 | Phase 3 (E-switch-ic) | Tamoxifen | Might have superior TTP |
Muss et al. 1994 | 1985-1990 | Phase 3 (E-switch-ic) | Tamoxifen | Might have superior OS |
Endocrine therapy
- Medroxyprogesterone acetate (MPA) 1000 mg PO or IM once per day or 500 mg PO twice per day
Continued indefinitely
Regimen variant #4, 1200 mg/day (high-dose)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Izuo et al. 1985 | 1981-1983 | Phase 3 (E-switch-ic) | Mepitiostane | Did not meet primary endpoint of ORR |
Endocrine therapy
- Medroxyprogesterone acetate (MPA) 400 mg PO three times per day
Continued indefinitely
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. link to original article contains dosing details in abstract 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. link to original article contains dosing details in abstract 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. link to original article 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. link to original article 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. link to original article contains dosing details in abstract 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. link to original article 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. link to original article 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. link to original article 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. link to original article contains dosing details in abstract 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. link to original article contains dosing details in abstract PubMed
Megestrol monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Muss et al. 1988 | 1981-1984 | Phase 3 (E-switch-ic) | Tamoxifen | Did not meet primary endpoint of ORR |
Lundgren et al. 1989 | NR | Phase 3 (C) | Aminoglutethimide | Did not meet primary endpoint of ORR |
Gill et al. 1993 | 1984-1989 | Phase 3 (E-switch-ic) | 1. Tamoxifen 2. Megestrol & Tamoxifen |
Did not meet endpoint of ORR |
Buzdar et al. 1996 | NR | Phase 3 (C) | Anastrozole | Seems to have inferior OS1 |
Russell et al. 1997 (SWOG S8312) | 1984-1990 | Phase 3 (C) | Aminoglutethimide, Hydrocortisone, Megestrol | Did not meet primary endpoint of OS |
Muss et al. 1990 | 1985-1988 | Phase 3 (C) | Megestrol; higher-dose | Seems to have inferior OS |
Stuart et al. 1996 | 1985-1988 | Phase 3 (E-switch-ic) | Tamoxifen | Did not meet endpoint of OS |
Abrams et al. 1999 (CALGB 8741) | 1987-1991 | Phase 3 (C) | Megestrol; higher-dose | Did not meet primary endpoint of ORR |
Buzdar et al. 1996 (Protocol 03) | 1989-1991 | Phase 3 (C) | Fadrozole | Did not meet primary endpoint of ORR |
Buzdar et al. 1996 (Protocol 06) | 1989-1991 | Phase 3 (C) | Fadrozole | Did not meet primary endpoint of ORR |
Thürlimann et al. 1997 (SAKK 20/90) | 1991-1995 | Phase 3 (C) | Formestane | Did not meet primary endpoint of TTF |
Goss et al. 1999 | 1991-1995 | Phase 3 (C) | Vorozole | Did not meet primary endpoint of ORR |
Jonat et al. 1996 | 1993-03 to 1994-09 | Phase 3 (C) | 1. Anastrozole; 1 mg/day | Seems to have inferior OS1 |
2. Anastrozole; 10 mg/day | Did not meet endpoint of OS | |||
Dombernowsky et al. 1998 (AR/BC2) | 1993-03 to 1994-09 | Randomized (C) | 1. Letrozole; 0.5 mg/day | Not reported |
2. Letrozole; 2.5 mg/day | Seems to have inferior OS | |||
Kaufmann et al. 2000 | 1995-1998 | Phase 3 (C) | Exemestane | Inconclusive whether equivalent ORR (primary endpoint) Seems to have inferior OS |
Buzdar et al. 2001 | NR | Phase 3 (C) | 1. Letrozole; 0.5 mg/day 2. Letrozole; 2.5 mg/day |
Did not meet primary endpoint of ORR |
1Reported efficacy for Jonat et al. 1996 & Buzdar et al. 1996 is based on the 1998 pooled update.
Endocrine therapy
- Megestrol (Megace) 160 mg PO once per day or 40 mg PO four times per day
Continued indefinitely
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. link to original article 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. link to original article 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. link to original article 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. link to original article contains dosing details in abstract 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. link to original article contains dosing details in abstract 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. link to original article 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. link to original article 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. link to original article 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. link to original article 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. link to original article 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. link to original article contains dosing details in abstract 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. link to original article 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. link to original article contains dosing details in manuscript 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. link to original article 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. link to original article 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. link to original article contains dosing details in abstract 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. link to original article 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. link to original article contains dosing details in abstract 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. link to original article contains dosing details in manuscript 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. link to original article contains dosing details in abstract PubMed
TAD (Tamoxifen)
TAD: Tamoxifen, Aminoglutethimide, Danazol
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Powles et al. 1984 | 1979-1983 | Phase 3 (E-esc) | Tamoxifen | Seems to have superior ORR |
Note: this patient population was not selected by hormone receptor status.
Endocrine therapy
- Tamoxifen (Nolvadex) 10 mg PO twice per day
- Aminoglutethimide (Cytadren) 250 mg PO three times per day
- Danazol (Danocrine) 100 mg PO three times per day
Supportive therapy
- Hydrocortisone (Cortef) 20 mg PO twice per day
Continued indefinitely
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. link to original article contains dosing details in manuscript PubMed
Metastatic disease, subsequent lines of therapy
Fluoxymesterone & Tamoxifen
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tormey et al. 1983 | NR | Randomized (E-esc) | Tamoxifen | Superior TTTF |
Endocrine therapy
- Fluoxymesterone (Halotestin) 7 mg/m2 PO twice per day
- Tamoxifen (Nolvadex) across a range of doses
Continued indefinitely
References
- Tormey DC, Lippman ME, Edwards BK, Cassidy JG. Evaluation of tamoxifen doses with and without fluoxymesterone in advanced breast cancer. Ann Intern Med. 1983 Feb;98(2):139-44. link to original article contains dosing details in abstract PubMed