Difference between revisions of "Breast cancer"
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===Regimen #1, 1 year {{#subobject:97eecb|Variant=1}}=== | ===Regimen #1, 1 year {{#subobject:97eecb|Variant=1}}=== | ||
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![[Levels_of_Evidence#Efficacy|Efficacy]] | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
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− | | rowspan="2" |[http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext | + | | rowspan="2" |[http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext Ejlertsen et al. 2013 (DBCG 82C)] |
| rowspan="2" style="background-color:#1a9851" |Phase III | | rowspan="2" style="background-color:#1a9851" |Phase III | ||
|[[#CMFT|CMFT]] | |[[#CMFT|CMFT]] | ||
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===Regimen #5, 5 years, with OFS {{#subobject:ed9421|Variant=1}}=== | ===Regimen #5, 5 years, with OFS {{#subobject:ed9421|Variant=1}}=== | ||
+ | OFS: '''<u>O</u>'''varian '''<u>F</u>'''unction '''<u>S</u>'''uppression | ||
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# Preliminary results from the cancer research campaign trial evaluating tamoxifen duration in women aged fifty years or older with breast cancer. Current Trials working Party of the Cancer Research Campaign Breast Cancer Trials Group. J Natl Cancer Inst. 1996 Dec 18;88(24):1834-9. Erratum in: J Natl Cancer Inst 1997 Apr 16;89(8):590. [https://www.ncbi.nlm.nih.gov/pubmed/8961973 PubMed] | # Preliminary results from the cancer research campaign trial evaluating tamoxifen duration in women aged fifty years or older with breast cancer. Current Trials working Party of the Cancer Research Campaign Breast Cancer Trials Group. J Natl Cancer Inst. 1996 Dec 18;88(24):1834-9. Erratum in: J Natl Cancer Inst 1997 Apr 16;89(8):590. [https://www.ncbi.nlm.nih.gov/pubmed/8961973 PubMed] | ||
## '''Update:''' Hackshaw A, Roughton M, Forsyth S, Monson K, Reczko K, Sainsbury R, Baum M. Long-term benefits of 5 years of tamoxifen: 10-year follow-up of a large randomized trial in women at least 50 years of age with early breast cancer. J Clin Oncol. 2011 May 1;29(13):1657-63. Epub 2011 Mar 21. [http://ascopubs.org/doi/full/10.1200/JCO.2010.32.2933 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21422412 PubMed] | ## '''Update:''' Hackshaw A, Roughton M, Forsyth S, Monson K, Reczko K, Sainsbury R, Baum M. Long-term benefits of 5 years of tamoxifen: 10-year follow-up of a large randomized trial in women at least 50 years of age with early breast cancer. J Clin Oncol. 2011 May 1;29(13):1657-63. Epub 2011 Mar 21. [http://ascopubs.org/doi/full/10.1200/JCO.2010.32.2933 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21422412 PubMed] | ||
− | # Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed] | + | # '''NSABP B-23:''' Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. [http://jco.ascopubs.org/content/19/4/931.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11181655 PubMed] |
# Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 PubMed] | # Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 PubMed] | ||
− | # Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. [http://www.nejm.org/doi/full/10.1056/NEJMoa040331 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15014181 PubMed] | + | # '''IES:''' Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. [http://www.nejm.org/doi/full/10.1056/NEJMoa040331 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15014181 PubMed] |
## '''Update:''' Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2960200-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17307102 PubMed] | ## '''Update:''' Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2807%2960200-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17307102 PubMed] | ||
## '''Update:''' Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.7899 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22042946 PubMed] | ## '''Update:''' Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.7899 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22042946 PubMed] | ||
− | # Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2917666-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15639680 PubMed] | + | # '''CALGB 9343:''' Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L; Cancer and Leukemia Group B; Radiation Therapy Oncology Group; Eastern Cooperative Oncology Group. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):971-7. [http://ascopubs.org/doi/full/10.1200/JCO.2012.45.2615 link to original article] [http://www.nejm.org/doi/full/10.1056/NEJMoa040587 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15342805 PubMed] |
+ | ## '''Update:''' Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013 Jul 1;31(19):2382-7. Epub 2013 May 20. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691356/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23690420 PubMed] | ||
+ | # '''ATAC:''' Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2917666-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15639680 PubMed] | ||
## '''Update:''' Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970385-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083636 PubMed] | ## '''Update:''' Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970385-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083636 PubMed] | ||
## '''Update:''' Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70257-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21087898 PubMed] | ## '''Update:''' Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70257-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21087898 PubMed] | ||
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## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. [http://jco.ascopubs.org/content/34/19/2232.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27161974 PubMed] | ## '''Update:''' Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. [http://jco.ascopubs.org/content/34/19/2232.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27161974 PubMed] | ||
# '''Review:''' Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2805%2966544-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15894097 PubMed] | # '''Review:''' Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2805%2966544-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15894097 PubMed] | ||
− | # Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed] | + | # '''INT-0102:''' Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. [http://jco.ascopubs.org/content/23/33/8313.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16293862 PubMed] |
− | # Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. [http://www.nejm.org/doi/full/10.1056/NEJMoa052258 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16382061 PubMed] | + | # '''BIG 1-98:''' Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. [http://www.nejm.org/doi/full/10.1056/NEJMoa052258 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16382061 PubMed] |
## '''Update:''' Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. [http://jco.ascopubs.org/content/25/5/486.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17200148 PubMed] | ## '''Update:''' Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. [http://jco.ascopubs.org/content/25/5/486.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17200148 PubMed] | ||
## '''Subgroup analysis:''' Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970386-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083065 PubMed] | ## '''Subgroup analysis:''' Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2807%2970386-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18083065 PubMed] | ||
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## '''Update:''' Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group.; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70270-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235950/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22018631 PubMed] | ## '''Update:''' Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group.; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70270-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235950/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22018631 PubMed] | ||
<!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. --> | <!-- Presented in part in abstract format at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006. --> | ||
− | # Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [http://jco.ascopubs.org/content/25/19/2664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17563395 PubMed] | + | # '''ARNO 95:''' Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. [http://jco.ascopubs.org/content/25/19/2664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17563395 PubMed] |
<!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). --> | <!-- Presented in part in abstract format in the Breast Cancer Research Treatment 100:S22, 2006 (suppl; abstr A40). --> | ||
− | # Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1965.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332472 PubMed] | + | # '''NSABP B-33:''' Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. [http://jco.ascopubs.org/content/26/12/1965.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18332472 PubMed] |
− | # van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21247627 PubMed] | + | # '''TEAM:''' van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62312-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21247627 PubMed] |
## '''Update:''' Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30419-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28732650 PubMed] | ## '''Update:''' Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30419-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28732650 PubMed] | ||
− | # Pritchard KI, Shepherd LE, Chapman JA, Norris BD, Cantin J, Goss PE, Dent SF, Walde D, Vandenberg TA, Findlay B, O'Reilly SE, Wilson CF, Han L, Piura E, Whelan TJ, Pollak MN. Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14. J Clin Oncol. 2011 Oct 10;29(29):3869-76. Epub 2011 Sep 12. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.7006 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21911723 PubMed] | + | # '''NCIC CTG MA.14:''' Pritchard KI, Shepherd LE, Chapman JA, Norris BD, Cantin J, Goss PE, Dent SF, Walde D, Vandenberg TA, Findlay B, O'Reilly SE, Wilson CF, Han L, Piura E, Whelan TJ, Pollak MN. Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14. J Clin Oncol. 2011 Oct 10;29(29):3869-76. Epub 2011 Sep 12. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.7006 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21911723 PubMed] |
## '''Update:''' Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. Epub 2015 Aug 15. [http://link.springer.com/article/10.1007%2Fs10549-015-3547-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681581/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26276354 PubMed] | ## '''Update:''' Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. Epub 2015 Aug 15. [http://link.springer.com/article/10.1007%2Fs10549-015-3547-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681581/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26276354 PubMed] | ||
<!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. --> | <!-- Presented in poster format at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL. --> | ||
− | # Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [http://ascopubs.org/doi/full/10.1200/JCO.2011.36.8993 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22271481 PubMed] | + | # '''ABCSG-8:'''' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. [http://ascopubs.org/doi/full/10.1200/JCO.2011.36.8993 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22271481 PubMed] |
− | # Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. Erratum in: Lancet. 2013 Mar 9;381(9869):804. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61963-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596060/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23219286 PubMed] | + | # '''ATLAS:''' Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. Erratum in: Lancet. 2013 Mar 9;381(9869):804. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61963-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596060/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23219286 PubMed] |
− | # Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. [http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23756360 PubMed] | + | # '''DBCG 82C:''' Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. [http://www.ejcancer.com/article/S0959-8049(13)00383-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23756360 PubMed] |
− | # Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1404037 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24881463 PubMed] | + | # '''TEXT/SOFT:''' Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1404037 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175521/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24881463 PubMed] |
## '''Update:''' Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. Epub 2014 Dec 11. [http://www.nejm.org/doi/full/10.1056/NEJMoa1412379 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341825/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25495490 PubMed] | ## '''Update:''' Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. Epub 2014 Dec 11. [http://www.nejm.org/doi/full/10.1056/NEJMoa1412379 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341825/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25495490 PubMed] | ||
# Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen breast cancer trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. [http://www.tandfonline.com/doi/full/10.1080/0284186X.2017.1400179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29165021 PubMed] | # Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen breast cancer trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. [http://www.tandfonline.com/doi/full/10.1080/0284186X.2017.1400179 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29165021 PubMed] |
Revision as of 19:24, 6 March 2018
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
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- Regimens for HER2 positive breast cancer are here.
- Regimens for Triple negative breast cancer (TNBC) are here.
- Regimens for BRCA-mutated breast cancer are here.
- Because docetaxel and paclitaxel are both often abbreviated as "T," we try to always make clear in the regimen name which agent is being used.
143 regimens on this page
330 variants on this page
|
Guidelines
ASCO
- 2016: Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression PubMed
- 2016: Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline PubMed
- 2016: Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline
- 2014: Adjuvant endocrine therapy for women with hormone receptor–positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update
ASCO/CCO
- 2017: Role of bone-modifying agents in metastatic breast cancer: an American Society of Clinical Oncology–Cancer Care Ontario focused guideline update PubMed
ESMO
- 2015: Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
ESO/ESMO
Older
NCCN
St Gallen Breast Guidelines
Neoadjuvant chemotherapy
AC
back to top |
AC: Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III | See link | See link |
Robidoux et al. 2013 (NSABP B-41) | Non-randomized portion of RCT | ||
Park et al. 2016 (I-SPY 2) | Non-randomized portion of RCT |
Note: patients in NSABP B-41 and I-SPY 2 were HER2-positive.
Preceding treatment
- NSABP B-40: T (Taxotere) x 4 versus TX x 4 versus TG x 4
- I-SPY 2: Neratinib & Paclitaxel x 12 wk versus TH x 12 wk
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen #2, 5 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ellis et al. 2011 (SWOG 0012) | Phase III (C) | Weekly doxorubicin & daily paclitaxel | Seems not superior |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 5 cycles
Subsequent treatment
- Paclitaxel x 12, then surgery
References
- Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol. 2011 Mar 10;29(8):1014-21. Epub 2011 Jan 10. link to original article contains verified protocol link to PMC article PubMed
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
- Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. Epub 2013 Oct 4. link to original article contains protocol PubMed
- Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains verified protocol link to PMC article PubMed
AC+Bev
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AC+Bev: Adriamycin (Doxorubicin), Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- T+Bev x 4 versus TX+Bev x 4 versus TG+Bev x 4
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Bevacizumab (Avastin) as follows:
- Cycles 1 & 2: 15 mg/kg IV once on day 1
- Cycles 3 & 4: none
21-day cycle for 4 cycles
Subsequent treatment
- Surgery, then adjuvant bevacizumab
References
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
ddAC
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ddAC: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide
Regimen
Study | Evidence |
---|---|
Burstein et al. 2005 | Non-randomized |
Park et al. 2016 (I-SPY 2) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in I-SPY 2 were HER2-positive.
Preceding treatment
- I-SPY 2: Neratinib & Paclitaxel x 12 wk versus TH x 12 wk
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
- Burstein et al. 2005: Darbepoetin alfa (Aranesp) 200 mcg SC once on day 1 for patients with Hb 10 to 12 g/dL; see paper for additional dose adjustments
14-day cycle for 4 cycles
Subsequent treatment
- Burstein et al. 2005: Optional Neoaduvant paclitaxel, then surgery or surgery, then adjuvant paclitaxel; this was not a randomization
- I-SPY 2: Surgery
References
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA; I-SPY 2 Investigators. Adaptive randomization of neratinib in early breast cancer. N Engl J Med. 2016 Jul 7;375(1):11-22. link to original article contains verified protocol link to PMC article PubMed
Docetaxel monotherapy
back to top |
D: Docetaxel
T: Taxotere (Docetaxel)
Regimen #1, 75 mg/m2 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- AC x 4, then surgery
Regimen #2, 100 mg/m2 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Earl et al. 2015 (ARTemis) | Phase III | Docetaxel & Bevacizumab | Seems to have inferior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen #3, 100 mg/m2 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2012 (GeparQuinto) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- EC x 4
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
- Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. link to original article contains verified protocol PubMed
Docetaxel & Bevacizumab
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Bev+D: Bevacizumab & Docetaxel
T+Bev: Taxotere (Docetaxel) & Bevacizumab
Regimen #1, docetaxel 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- AC+Bev x 4, then surgery
Regimen #2, docetaxel 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Earl et al. 2015 (ARTemis) | Phase III | Docetaxel | Seems to have superior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. A total of four bevacizumab doses are given, with the fourth given with the first cycle of FEC.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
- Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. link to original article contains verified protocol PubMed
EC
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EC: Epirubicin & Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
von Minckwitz et al. 2012 (GeparQuinto) | Phase III | See link | See link |
Untch et al. 2016 (GBG 69) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- GBG 69: nab-Paclitaxel x 4 versus Paclitaxel x 4
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- GeparQuinto: Docetaxel, then surgery
- GBG 69: Surgery
References
- von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M; German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie–Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012 Jan 26;366(4):299-309. link to original article contains verified protocol PubMed
- Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG).; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. link to original article contains verified protocol PubMed
FEC
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FEC: Fluorouracil, Epirubicin, Cyclophosphamide
Regimen #1, 500/75/500 ("FEC-75")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 2013 (ACOSOG Z1041) | Phase III | See link | See link |
Note that patients in this trial had HER2-positive breast cancer. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) x 12 wk, then surgery
Regimen #2, 500/100/500 x 3
Study | Evidence |
---|---|
Earl et al. 2015 (ARTemis) | Non-randomized portion of RCT |
Note that for the patients randomized to the bevacizumab arm, a fourth dose was given with the first cycle of FEC. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Docetaxel & Bevacizumab x 3 versus Docetaxel x 3
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- Surgery
Regimen #3, 500/100/500 x 4
Study | Evidence |
---|---|
Kelly et al. 2012 | Non-randomized portion of RCT |
This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Weekly paclitaxel x 12 versus XT
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Surgery
References
- Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. link to original article PubMed
- Update: Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. link to original article PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- Buzdar AU, Suman VJ, Meric-Bernstam F, Leitch AM, Ellis MJ, Boughey JC, Unzeitig G, Royce M, McCall LM, Ewer MS, Hunt KK; American College of Surgeons Oncology Group investigators. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1317-25. Epub 2013 Nov 13. link to original article link to PMC article contains verified protocol PubMed
- Earl HM, Hiller L, Dunn JA, Blenkinsop C, Grybowicz L, Vallier AL, Abraham J, Thomas J, Provenzano E, Hughes-Davies L, Gounaris I, McAdam K, Chan S, Ahmad R, Hickish T, Houston S, Rea D, Bartlett J, Caldas C, Cameron DA, Hayward L; ARTemis Investigators. Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):656-66. Epub 2015 May 11. link to original article contains verified protocol PubMed
Paclitaxel monotherapy
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T: Taxol (Paclitaxel)
Regimen #1, weekly paclitaxel
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ellis et al. 2011 (SWOG 0012) | Non-randomized portion of RCT | ||
Kelly et al. 2012 | Phase III (C) | XT | Seems not superior |
Untch et al. 2016 (GBG 69) | Phase III | nab-Paclitaxel | Inferior pCR rate |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- SWOG 0012: AC x 5 versus weekly doxorubicin & daily cyclophosphamide
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
12-week course
Subsequent treatment
Regimen #2, bi-weekly paclitaxel
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Burstein et al. 2005 | Non-randomized | ||
Earl et al. 2013 (Neo-tAnGo) | Phase III (C) | EC, then T EC, then TG |
Seems to have superior pCR rate |
TG | Seems not superior |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Burstein et al. 2005: ddAC x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
14-day cycle for 4 cycles
Subsequent treatment
- Burstein et al. 2005: Surgery
- Neo-tAnGo: EC
References
- Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005 Jun 1;23(16):3676-85. Epub 2005 Feb 28. link to original article PubMed
- Update: Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007 Jan 1;13(1):228-33. link to original article PubMed
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Ellis GK, Barlow WE, Gralow JR, Hortobagyi GN, Russell CA, Royce ME, Perez EA, Lew D, Livingston RB. Phase III comparison of standard doxorubicin and cyclophosphamide versus weekly doxorubicin and daily oral cyclophosphamide plus granulocyte colony-stimulating factor as neoadjuvant therapy for inflammatory and locally advanced breast cancer: SWOG 0012. J Clin Oncol. 2011 Mar 10;29(8):1014-21. Epub 2011 Jan 10. link to original article contains verified protocol link to PMC article PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. Epub 2013 Dec 19. link to original article contains verified protocol PubMed
- Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG).; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. link to original article contains verified protocol PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Untch et al. 2016 (GBG 69) | Phase III | Paclitaxel | Superior pCR rate |
Note: this is the dose after study amendment due to increased treatment discontinuation and sensory neuropathy. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Subsequent treatment
References
- Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kümmel S, Hilfrich J, Warm M, Paepke S, Just M, Hanusch C, Hackmann J, Blohmer JU, Clemens M, Darb-Esfahani S, Schmitt WD, Dan Costa S, Gerber B, Engels K, Nekljudova V, Loibl S, von Minckwitz G; German Breast Group (GBG).; Arbeitsgemeinschaft Gynäkologische Onkologie—Breast (AGO-B) Investigators. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. Epub 2016 Feb 8. 2016 Mar;17(3):345-56. link to original article contains verified protocol PubMed
Neoadjuvant endocrine therapy
Anastrozole monotherapy
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Regimen
Study | Evidence | Efficacy |
---|---|---|
Ellis et al. 2011 (ACOSOG Z1031) | Screening Phase II | cRR: 69% (95% CI, 60-77) |
Note: ACOSOG Z1031 was randomized but with the intent to select candidates for phase III trials; efficacy comparisons were not made.
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
16- to 18-week course
Subsequent treatment
- Surgery
References
- Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031. J Clin Oncol. 2011 Jun 10;29(17):2342-9. Epub 2011 May 9. link to original article link to PMC article contains verified protocol PubMed
Anastrozole & Goserelin
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Masuda et al. 2012 (STAGE) | Phase III | Goserelin & Tamoxifen | Superior RR |
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
- Goserelin (Zoladex) 3.6 mg IM depot once per month
24-week course
Subsequent treatment
- Surgery
References
- Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. Epub 2012 Jan 20. link to original article contains protocol PubMed
Goserelin & Tamoxifen
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Masuda et al. 2012 (STAGE) | Phase III | Goserelin & Tamoxifen | Inferior RR |
Endocrine therapy
- Goserelin (Zoladex) 3.6 mg IM depot once per month
- Tamoxifen (Nolvadex) 20 mg PO once per day
24-week course
Subsequent treatment
- Surgery
References
- Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, Nishimura R, Iwase H, Kamigaki S, Takei H, Noguchi S. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012 Apr;13(4):345-52. Epub 2012 Jan 20. link to original article contains protocol PubMed
Letrozole monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Eiermann et al. 2001 (P024)) | Phase III | Tamoxifen | Superior ORR |
Ellis et al. 2011 (ACOSOG Z1031) | Screening Phase II | cRR: 75% (95% CI, 66-82) |
Note: ACOSOG Z1031 gave a total treatment duration of 16 to 18 weeks, which is approximately 4 months. Also, this trial was randomized but with the intent to select candidates for phase III trials; efficacy comparisons were not made.
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
4-month course
Subsequent treatment
- Surgery
References
- Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, Mauriac L, Ellis M, Lassus M, Chaudri-Ross HA, Dugan M, Borgs M; Letrozole Neo-Adjuvant Breast Cancer Study Group. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol. 2001 Nov;12(11):1527-32. link to original article contains protocol PubMed
- Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, Parker JS, Luo J, DeSchryver K, Allred DC, Esserman LJ, Unzeitig GW, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Watson MA, Leitch M, Hunt K, Olson JA. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031. J Clin Oncol. 2011 Jun 10;29(17):2342-9. Epub 2011 May 9. link to original article link to PMC article contains verified protocol PubMed
Neoadjuvant response criteria
Clinical response rate (cRR)
Although fairly dated, some trials such as ACOSOG Z1031 make use of the WHO criteria for response to neoadjuvant therapy. Included here primarily for historical purposes.
References
- Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. link to original article PubMed
Miller-Payne scoring system
- Grade 1: No change or some changes to individual malignant cells, but no reduction in overall cellularity
- Grade 2: Minor loss of tumor cells (up to 30%), but overall cellularity still high
- Grade 3: An estimated 30 to 90% reduction in the number of tumor cells
- Grade 4: Marked disappearance of tumor cells such that only small clusters or widely dispersed individual cells remain (loss of greater than 90% of tumor cells)
- Grade 5: No invasive cancer cells identifiable in sections from the site of the tumor (carcinoma in situ may be present)
References
- Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, Schofield A, Heys SD. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003 Oct;12(5):320-7. link to original article PubMed
Residual cancer burden (RCB)
- The RCB is calculated as follows: RCB = 1.4 (finv*dprim)0.17 + [4(1 - 0.75LN)dmet]0.17
- where dprim is derived from the bidimensional diameters of the primary tumor bed in the resected specimen, finv is the proportion of the primary tumor bed that contains invasive carcinoma, LN is the number of axillary lymph nodes containing metastatic carcinoma, and dmet is the diameter of the largest metastasis in an axillary lymph node.
- The cut-off points are 1.36 and 3.28.
References
- Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007 Oct 1;25(28):4414-22. Epub 2007 Sep 4. link to original article PubMed
Residual disease in breast and nodes (RDBN)
- Level 1: pCR in breast and nodes with or without in situ carcinoma
- Levels 2 to 4: Residual disease, calculated as 0.2 (residual breast tumor size in cm) + index of involved nodes (0 for no positive nodes, 1 for 1 to 4 positive nodes, 2 for 5 to 7 positive nodes, and 3 for 8 positive nodes) + the Scarff–Bloom–Richardson grade (1, 2, or 3). The cut-off points are 3 and 4.3.
References
- Chollet P, Abrial C, Durando X, Thivat E, Tacca O, Mouret-Reynier MA, Leheurteur M, Kwiatkowski F, Dauplat J, Penault-Llorca F. A new prognostic classification after primary chemotherapy for breast cancer: residual disease in breast and nodes (RDBN). Cancer J. 2008 Mar-Apr;14(2):128-32. link to original article PubMed
Sataloff's classification
- Breast:
- T-A: Total or nearly total therapeutic effect
- T-B: Greater than 50% therapeutic effect
- T-C: Less than 50% therapeutic effect
- T-D: No therapeutic effect
- Lymph node:
- N-A: Therapeutic effect but no metastasis
- N-B: No metastasis, no therapeutic effect
- N-C: Therapeutic effect but metastasis
- N-D: Metastasis, no therapeutic effect
References
- Sataloff DM, Mason BA, Prestipino AJ, Seinige UL, Lieber CP, Baloch Z. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. J Am Coll Surg. 1995 Mar;180(3):297-306. PubMed
Tumor response ratio
Calculated as follows: Residual breast disease observed upon pathologic examination divided by the size of the tumor on the pre-neoadjuvant therapy image.
- TRR = 0: pathologic complete response (pCR)
- TRR greater than 0 up to 0.4: strong partial response
- TRR greater than 0.4 up to 1.0: weak partial response (WPR)
- TRR greater than 1.0: tumor growth
References
- Miller M, Ottesen RA, Niland JC, Kruper L, Chen SL, Vito C. Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2014 Oct;21(10):3317-23. Epub 2014 Jul 25. link to original article PubMed
ypTNM staging
This system is proprietary to the AJCC. Please visit their site or consult the AJCC Manual for further details.
Adjuvant chemotherapy
AC
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AC: Adriamycin (Doxorubicin) and Cyclophosphamide
CA: Cyclophosphamide and Adriamycin (Doxorubicin)
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fisher et al. 2001 (NSABP B-23) | Phase III | CMF | Seems not superior |
Henderson et al. 2003 (INT 0148/CALGB 9344) | Phase III | High-dose AC Very-high-dose AC |
Seems not superior |
Citron et al. 2003 (CALGB 9741) | Phase III | A ddA ddAC |
See link |
Van Pelt et al. 2003 | Phase II | ||
Mamounas et al. 2005 (NSABP B-28) | Non-randomized portion of RCT | ||
Romond et al. 2005 (NSABP B-31/NCCTG N9831) | Non-randomized portion of RCT | ||
Jones et al. 2006 (US Oncology Trial 9735) | Phase III | TC | Seems to have inferior OS |
Sparano et al. 2008 (ECOG E1199) | Non-randomized portion of RCT | ||
Eiermann et al. 2011 (BCIRG-005) | Phase III | See link | See link |
Slamon et al. 2011 (BCIRG 006) | Phase III | See link | See link |
Patients in Van Pelt et al. 2003, NSABP B-31, NCCTG N9831, and BCIRG 006 were HER2-positive.
Preceding treatment
- Van Pelt et al. 2003: Neoadjuvant TH, then surgery
- INT 0148/CALGB 9344: Surgery, within 84 days
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NSABP B-23: Tamoxifen versus placebo
- Van Pelt et al. 2003: H
- INT 0148/CALGB 9344 and NSABP B-28: T (Taxol) versus no further therapy
- CALGB 9741: T (Taxol)
- NSABP B-31: T (Taxol) versus TH (Taxol)
- NCCTG N9831: T (Taxol) versus T (Taxol), then H versus TH (Taxol)
- ECOG E1199: Docetaxel q3wk versus Docetaxel weekly versus Paclitaxel q3wk versus Paclitaxel weekly
- BCIRG-005: T (Taxotere)
- BCIRG 006: T (Taxol) versus TH (Taxol)
Regimen #2, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for AC are given in the protocol, replicated here.
Preceding treatment
- Surgery
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
- Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
- Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
- Van Pelt AE, Mohsin S, Elledge RM, Hilsenbeck SG, Gutierrez MC, Lucci A Jr, Kalidas M, Granchi T, Scott BG, Allred DC, Chang JC. Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. Clin Breast Cancer. 2003 Dec;4(5):348-53. PubMed
- Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed
- Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed
- Update: Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. link to original article link to PMC article PubMed
- Update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. link to original article link to PMC article PubMed
- Update and HRQoL analysis: Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. link to original article link to PMC article PubMed
- Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. link to original article PubMed
- Update: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. link to original article PubMed
- Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. link to original article link to PMC article PubMed
- Update: Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. Epub 2015 Jun 15. link to original article link to PMC article PubMed
- Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. link to original article contains verified protocol PubMed
- Update: Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. link to original article PubMed
- Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article PubMed
- Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. link to original article PubMed
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
Bevacizumab monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bear et al. 2012 (NSABP B-40) | Phase III | See link | See link |
Preceding treatment
- Neoadjuvant AC+Bev x 4, then surgery
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for 10 cycles
References
- Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. link to original article link to PMC article PubMed
- Update: Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. Epub 2015 Aug 10. Erratum in: Lancet Oncol. 2015 Dec;16(16):e589. link to original article link to PMC article PubMed
Capecitabine monotherapy
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Regimen #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cameron et al. 2017 (TACT2) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- ddE x 4 versus Epirubicin x 4
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycle for 4 cycles
Regimen #2, 6 to 8 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Masuda et al. 2017 | Phase III | Standard therapy | Superior OS |
All patients in this study had residual disease at time of surgical resection. Concomitant endocrine therapy was allowed.
Preceding treatment
- Neoadjuvant chemotherapy containing anthracycline, taxane, or both, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycle for 6 to 8 cycles
References
- Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147-2159. link to original article contains verified protocol PubMed
- Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. link to original article link to PMC article contains verified protocol PubMed
CMF
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CMF: Cyclophosphamide, Methotrexate, Fluorouracil
Regimen #1, IV cyclophosphamide
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schmid et al. 2007 (TABLE) | Phase III | Leuprolide | Inferior OS |
Preceding treatment
- Surgery, within 6 weeks
Chemotherapy
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Regimen #2, classic CMF (IV) x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT) | Phase III | Epirubicin, then CMF x 4 | Inferior OS |
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Regimen #3, classic CMF (PO) x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Levine et al. 1998 (NCIC CTG MA5) | Phase III | CEF | Inferior RFS |
Fisher et al. 2001 (NSABP B-23) | Phase III | AC | Seems not superior |
Piccart et al. 2001 | Phase III | Full-dose EC | Seems not superior |
Moderate-dose EC | Not reported | ||
Hutchins et al. 2005 (INT-0102) | Phase III | CAF | Seems to have inferior OS |
Poole et al. 2006 (NEAT) | Phase III | Epirubicin, then CMF x 4 | Inferior OS |
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
Subsequent treatment
Regimen #4, classic CMF (PO) x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT) | Phase III | See link | See link |
Cameron et al. 2017 (TACT2) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Epirubicin x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 4 cycles
Regimen #5, classic CMF (IV) x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT) | Phase III | See link | See link |
Cameron et al. 2017 (TACT2) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Epirubicin x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 4 cycles
Regimen #6, modified CMF x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (BR9601) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Epirubicin x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Methotrexate (MTX) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen #7, modified CMF x 8
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (BR9601) | Phase III | Epirubicin, then CMF x 4 | Inferior OS |
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Methotrexate (MTX) 50 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Regimen #8, classic CMF x 12
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bonadonna et al. 1976 | Phase III | Observation | Superior RFS |
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1 & 8
28-day cycle for 12 cycles
References
- Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. link to original article contains verified protocol PubMed
- Update: Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes. Updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. link to original article PubMed
- Update: Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. PubMed
- Update: Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. link to original article PubMed
- Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. PubMed
- Update: Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. link to original article PubMed
- Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients. An Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. link to original article PubMed
- Coombes RC, Bliss JM, Wils J, Morvan F, Espié M, Amadori D, Gambrosier P, Richards M, Aapro M, Villar-Grimalt A, McArdle C, Pérez-López FR, Vassilopoulos P, Ferreira EP, Chilvers CE, Coombes G, Woods EM, Marty M. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group. J Clin Oncol. 1996 Jan;14(1):35-45. link to original article PubMed
- Review: Goldhirsch A, Colleoni M, Coates AS, Castiglione-Gertsch M, Gelber RD. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol. 1998 May;9(5):489-93. link to original article contains protocol PubMed
- Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1998 Aug;16(8):2651-8. link to original article PubMed
- Update: Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N; National Cancer Institute of Canada Clinical Trials Group. Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol. 2005 Aug 1;23(22):5166-70. link to original article PubMed
- Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
- Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. link to original article PubMed
- Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. link to original article PubMed
- Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. link to original article PubMed
- Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Cold S, Edlund P, Ewertz M, Jensen BB, Kamby C, Nordenskjold B, Bergh J. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer. Eur J Cancer. 2007 Mar;43(5):877-84. Epub 2007 Feb 16. link to original article PubMed
- Schmid P, Untch M, Kossé V, Bondar G, Vassiljev L, Tarutinov V, Lehmann U, Maubach L, Meurer J, Wallwiener D, Possinger K. Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study. J Clin Oncol. 2007 Jun 20;25(18):2509-15. link to original article contains verified protocol PubMed
- Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article PubMed
CMFT
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CMFT: Cyclophosphamide, Methotrexate, Fluorouracil, Tamoxifen
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Eljertsen et al. 2013 (DBCG 82C) | Phase III | Tamoxifen | Superior DFS |
Tamoxifen & RT | Not reported |
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Methotrexate (MTX) 40 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Tamoxifen (Nolvadex) 30 mg PO once per day
28-day cycle for 9 cycles (tamoxifen continued for one year total)
References
- Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. link to original article contains verified protocol PubMed
DC
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DC: Docetaxel and Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ejlertsen et al. 2017 (DBCG 07-READ) | Phase III | EC, then D | Seems not superior |
Patients were TOP2A normal as determined by FISH.
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed
ddA
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ddA: dose-dense Adriamycin (Doxorubicin)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III | See link | See link |
Kahan et al. 2005 | Phase II |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
Supportive medications
14-day cycle for 4 cycles
Subsequent treatment
References
- Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
- Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. link to original article PubMed
- Update: Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. link to original article PubMed
ddAC
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ddAC: dose-dense Adriamycin (Doxorubicin) and Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III | See link | See link |
Burstein et al. 2005 | Non-randomized | ||
Dang et al. 2008 | Phase II | ||
Shulman et al. 2012 (CALGB 40101) | Phase III | ddAC x 6 | Seems not superior |
Paclitaxel x 4 | Seems not superior | ||
Paclitaxel x 6 | Seems not superior | ||
Swain et al. 2013 (NSABP B-38) | Phase III | See link | See link |
Note: CALGB 40101 originally specified 21-day cycles but was amended to 14-day cycles after results of CALGB 9741 were available. Patients in Dang et al. 2008 had HER2-positive breast cancer.
Preceding treatment
- Surgery
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- (varies depending on reference):
- CALGB 9741:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
- Note: Citron et al. 2003 says the schedule was "filgrastim days 3 to 10 of each cycle (a total of seven doses)," so it is unclear whether 7 or 8 doses was actually used).
- Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
- Burstein et al. 2005 and Dang et al. 2008:
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2, given 24 hours after chemotherapy
- Burstein et al. 2005:
- Darbepoetin alfa (Aranesp) 200 mcg SC once on day 1 for patients with Hb 10 to 12 g/dL; see Burstein et al. 2005 for additional dose adjustments
- CALGB 40101: one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC, administered once 24 to 36 hours after chemotherapy
14-day cycle for 4 cycles
Subsequent treatment
- CALGB 9741 and Burstein et al. 2005: Paclitaxel x 4
- Dang et al. 2008: ddTH (Taxol)
- NSABP B-38: dose-dense paclitaxel x 4 versus ddPG x 4
Regimen #2, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for ddAC are given in the protocol, replicated here.
Preceding treatment
- Surgery
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive medications
- G-CSF support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Dang C, Fornier M, Sugarman S, Troso-Sandoval T, Lake D, D'Andrea G, Seidman A, Sklarin N, Dickler M, Currie V, Gilewski T, Moynahan ME, Drullinsky P, Robson M, Wasserheit-Leiblich C, Mills N, Steingart R, Panageas K, Norton L, Hudis C. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1216-22. link to original article contains verified protocol PubMed
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF link to PMC article PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
ddC
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ddC: dose-dense Cyclophosphamide
Regimen #1, 600 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- ddT x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg (rounded to either 300 or 480 mcg) SC once per day on days 3 to 10
- Note: Citron et al. 2003 says the schedule was "filgrastim days 3 to 10 of each cycle (a total of seven doses)," so it is unclear whether 7 or 8 doses was actually used).
14-day cycle for 4 cycles
Regimen #2, 800 mg/m2
Study | Evidence |
---|---|
Kahan et al. 2005 | Phase II |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- ddT x 4
Chemotherapy
- Cyclophosphamide (Cytoxan) 800 mg/m2 IV once on day 1
Supportive medications
14-day cycle for 4 cycles
References
- Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
- Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. link to original article PubMed
- Update: Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. link to original article PubMed
ddEC
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ddEC: dose-dense Epirubicin and Cyclophosphamide
Regimen #1, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for ddEC are given in the protocol, replicated here.
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
Supportive medications
- G-CSF support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Del Mastro et al. 2015 (GIM2) | Phase III | ddFEC | Seems not superior |
EC FEC |
Superior OS |
To be completed; insufficient details in abstract for dosing.
Preceding treatment
- Surgery
Chemotherapy
Supportive medications
Subsequent treatment
References
- Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. link to original article PubMed
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
ddFEC
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ddFEC: dose-dense Fluorouracil, Epirubicin, Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2016 (HORG CT/07.17) | Phase III | See link | See link |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
Supportive medications
- Filgrastim or Pegfilgrastim support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
Subsequent treatment
References
- Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article contains verified protocol PubMed
ddT (Taxol)
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ddT: dose-dense Taxol (Paclitaxel)
ddP: dose-dense Paclitaxel
Regimen #1, 175 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Citron et al. 2003 (CALGB 9741) | Phase III | See link | See link |
Burstein et al. 2005 | Non-randomized | ||
Shulman et al. 2012 (CALGB 40101) | Phase III | ddAC x 4 | Seems not superior |
ddAC x 6 | Seems not superior | ||
ddT x 6 | Seems not superior | ||
Swain et al. 2013 (NSABP B-38) | Phase III | See link | See link |
Note: in CALGB 40101, this is the dosing after a mid-protocol amendment in 2003.
Preceding treatment
- CALGB 9741: ddA x 4 or ddAC x 4
- Burstein et al. 2005: Neoadjuvant ddAC and surgery or adjuvant ddAC
- CALGB 40101: Surgery, within 90 days
- NSABP B-38: ddAC x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
Supportive medications
- Diphenhydramine (Benadryl) 12.5 to 50 mg IV 30 to 60 minutes prior to paclitaxel
- One of the following H2 blockers:
- Ranitidine (Zantac) 50 mg IV 30 to 60 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV 30 to 60 minutes prior to paclitaxel
- Famotidine (Pepcid) 20 mg IV 30 to 60 minutes prior to paclitaxel
- One of the following dexamethasone choices:
- Dexamethasone (Decadron) 10 mg IV less than 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 10 mg PO greater than 60 minutes prior to paclitaxel
- Dexamethasone (Decadron) 20 mg PO 6 hours and 12 hour prior to paclitaxel
- Recommended growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg (rounded to 300 mcg or 480 mcg, whichever is closer) SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Sargramostim (Leukine) 250 to 500 mcg/m2 SC once per day on days 3 to 10; may be discontinued before day 10 if ANC has recovered to an "acceptable range, as determined by the treating physician"
- Pegfilgrastim (Neulasta) 6 mg SC, administered once 24 to 36 hours after chemotherapy
14-day cycle for 4 cycles
Subsequent treatment
- CALGB 9741: ddC x 4 (if preceded by ddA)
Regimen #2, 200 mg/m2
Study | Evidence |
---|---|
Kahan et al. 2005 | Phase II |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- ddA x 4
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours day 1
Supportive medications
14-day cycle for 4 cycles
Subsequent treatment
References
- Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
- Kahan Z, Uhercsak G, Hajnal-Papp R, Boda K, Thurzo L. Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer. Oncology. 2005;68(4-6):446-53. Epub 2005 Jul 13. link to original article PubMed
- Update: Kelemen G, Uhercsák G, Ormándi K, Eller J, Thurzó L, Kahán Z. Long-term efficiency and toxicity of adjuvant dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy in high-risk breast cancer. Oncology. 2010;78(3-4):271-3. Epub 2010 Jun 7. link to original article PubMed
- Burstein HJ, Parker LM, Keshaviah A, Doherty J, Partridge AH, Schapira L, Ryan PD, Younger J, Harris LN, Moy B, Come SE, Schumer ST, Bunnell CA, Haldoupis M, Gelman R, Winer EP. Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy. J Clin Oncol. 2005 Nov 20;23(33):8340-7. link to original article contains verified protocol PubMed
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF link to PMC article PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed
ddT (Taxotere)
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ddT: dose-dense Taxotere (Docetaxel)
ddD: dose-dense Docetaxel
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2016 (HORG CT/07.17) | Phase III | See link | See link |
Preceding treatment
- ddFEC x 4
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Supportive medications
- Filgrastim or Pegfilgrastim support (drug/dose/schedule not specified)
14-day cycle for 4 cycles
References
- Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article contains verified protocol PubMed
Docetaxel monotherapy
back to top |
D: Docetaxel
T: Taxotere (Docetaxel)
dT: doceTaxel
Regimen #1, 35 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sparano et al. 2008 (ECOG E1199) | Phase III | Paclitaxel, q3wk dosing | Seems not superior |
Paclitaxel, weekly dosing Docetaxel, q3wk dosing |
Not reported |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- AC x 4
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV over 60 minutes once per week
12-week course
Regimen #2, 75 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2017 | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Epirubicin x 4
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 4 cycles
Regimen #3, 80 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2009 (FinXX) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 80 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- CEF x 3
Regimen #4, 100 mg/m2 q3wk x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2006 (FinHer) | Phase III | TH (Taxotere) VH |
Seems not superior |
Vinorelbine | Superior DDFS | ||
Roché et al. 2006 (FNCLCC PACS 01) | Phase III | See link | See link |
Coombes et al. 2011 (DEVA) | Phase III | See link | See link |
Ejlertsen et al. 2017 (DBCG 07-READ) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in FinHer without HER2/neu amplification were only randomized to this or the vinorelbine arm. Patients in DBCG 07-READ were TOP2A normal as determined by FISH.
Preceding treatment
- FinHer: Breast surgery with axillary lymph node dissection or sentinel lymph node biopsy, within 12 weeks
- FNCLCC PACS 01: FEC x 3
- DEVA: Epirubicin x 3
- DBCG 07-READ: EC x 3
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- FinHer: FEC
Regimen #5, 100 mg/m2 q3wk x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sparano et al. 2008 (ECOG E1199) | Phase III | Paclitaxel, q3wk dosing | Seems to have superior DFS |
Paclitaxel, weekly dosing Docetaxel, weekly dosing |
Not reported | ||
Eiermann et al. 2011 (BCIRG-005) | Phase III | See link | See link |
Slamon et al. 2011 (BCIRG 006) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in BCIRG 006 were HER2-positive.
Preceding treatment
- AC x 4
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycle for 4 cycles
References
- Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article contains verified protocol PubMed
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
- Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. link to original article PubMed
- Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. link to original article link to PMC article PubMed
- Update: Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. Epub 2015 Jun 15. link to original article link to PMC article PubMed
- Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article PubMed
- Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. link to SD article PubMed
- Update: Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. link to original article PubMed
- Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. link to original article contains protocol PubMed
- Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. link to original article contains verified protocol PubMed
- Update: Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. link to original article PubMed
- Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. link to original article link to PMC article PubMed
- Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. link to original article PubMed
- Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. link to original articlecontains verified protocol PubMed
- Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed
EC
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EC: Epirubicin and Cyclophosphamide
Regimen #1, 90/600 x 4
Study | Evidence |
---|---|
Earl et al. 2017 (tAnGo) | Non-randomized portion of RCT |
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Paclitaxel versus TG
Regimen #2, 90/600 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ejlertsen et al. 2017 (DBCG 07-READ) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients were TOP2A normal as determined by FISH.
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen #3, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for EC are given in the protocol, replicated here.
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 90 to 120 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
Regimen #4, 100/830
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Piccart et al. 2001 | Phase III | CMF | Seems not superior |
Moderate-dose EC | Seems to have superior OS |
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 830 mg/m2 IV once on day 1
21-day cycle for 8 cycles
Regimen #5, 60/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Piccart et al. 2001 | Phase III | CMF | Not reported |
High-dose EC | Seems to have inferior OS |
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 8 cycles
References
- Piccart MJ, Di Leo A, Beauduin M, Vindevoghel A, Michel J, Focan C, Tagnon A, Ries F, Gobert P, Finet C, Closon-Dejardin MT, Dufrane JP, Kerger J, Liebens F, Beauvois S, Bartholomeus S, Dolci S, Lobelle JP, Paesmans M, Nogaret JM. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10. link to original article PubMed
- Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. link to original article PubMed
- Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. link to original article contains protocol PubMed
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
- Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant cyclophosphamide and docetaxel with or without epirubicin for early TOP2A-normal breast cancer: DBCG 07-READ, an open-label, phase III, randomized trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. Epub 2017 Jun 29. link to original article contains verified protocol PubMed
Epirubicin monotherapy
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Regimen #1, 50 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 2011 (DEVA) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Complete surgical excision
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once per day on days 1 & 8
28-day cycle for 3 cycles
Subsequent treatment
- Docetaxel x 3
Regimen #2, 90 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2017 | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV over 5 to 15 minutes once on day 1
21-day cycle for 4 cycles
Subsequent treatment
Regimen #3, 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Poole et al. 2006 (NEAT/BR9601) | Phase III | See link | See link |
Cameron et al. 2017 (TACT2) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Complete surgical excision
Chemotherapy
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NEAT and BR9601: CMF
- TACT2: capecitabine versus CMF
References
- Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. link to original article contains verified protocol PubMed
- Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article PubMed
- Coombes RC, Bliss JM, Espie M, Erdkamp F, Wals J, Tres A, Marty M, Coleman RE, Tubiana-Mathieu N, den Boer MO, Wardley A, Kilburn LS, Cooper D, Thomas MW, Reise JA, Wilkinson K, Hupperets P. Randomized, phase III trial of sequential epirubicin and docetaxel versus epirubicin alone in postmenopausal patients with node-positive breast cancer. J Clin Oncol. 2011 Aug 20;29(24):3247-54. Epub 2011 Jul 18. link to original article contains protocol PubMed
- Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, Agrawal R, Banerji J, Bertelli G, Bloomfield D, Brunt AM, Earl H, Ellis P, Gaunt C, Gillman A, Hearfield N, Laing R, Murray N, Couper N, Stein RC, Verrill M, Wardley A, Barrett-Lee P, Bliss JM; TACT2 Investigators. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017 Jul;18(7):929-945. Epub 2017 Jun 7. link to original article link to PMC article contains verified protocol PubMed
- Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Fountzilas G, Rigas G, Varthalitis I, Kalbakis K, Agelaki S, Hatzidaki D, Georgoulias V. Sequential vs concurrent epirubicin and docetaxel as adjuvant chemotherapy for high-risk, node-negative, early breast cancer: an interim analysis of a randomised phase III study from the Hellenic Oncology Research Group. Br J Cancer. 2017 Jul 11;117(2):164-170. Epub 2017 Jun 22. link to original articlecontains verified protocol PubMed
FAC
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FAC: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide
CAF: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil
Regimen #1, 500/50/500
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martin et al. 2005 (BCIRG 001) | Phase III | TAC | Inferior OS |
Martín et al. 2010 (GEICAM 9805) | Phase III | TAC | Inferior DFS |
Martín et al. 2013 (GEICAM/2003-02) | Phase III | FAC-wP | Seems to have inferior DFS |
Preceding treatment
- Surgery
Chemotherapy
Infusion times per Martin et al. 2005 (BCIRG 001).
- Fluorouracil (5-FU) 500 mg/m2 IV over 15 minutes once on day 1, given second
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 15 minutes once on day 1, given first
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV over 1 to 5 minutes once on day 1, given third
- A HemOnc.org user reached out to us and said their institutional practice is to infuse cyclophosphamide over 20 to 30 minutes to decrease the likelihood of head and sinus pain.
Supportive medications
- If patients had febrile neutropenia or infection: Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 14 of every cycle
- G-CSF not originally routinely administered unless patients had febrile neutropenia:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 4 to 11
- OR Lenograstim (Granocyte) 150 mcg/m2 SC once per day on days 4 to 11
21-day cycle for 6 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hutchins et al. 2005 (INT-0102) | Phase III | CMF | Seems to have superior OS |
Preceding treatment
- Surgery
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 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
28-day cycle for 6 cycles
Treatment in
Regimen #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Buzdar et al. 1984 | Phase III | FAC + BCG | Seems not superior |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
21-day cycles until cumulative doxorubicin dose of 300 mg/m2 reached.
After reaching cumulative maximum doxorubicin, patients would go on to receive maintenance CMF. This is now obsolete.
Regimen #4, with range
Study | Evidence |
---|---|
von Minckwitz et al. 2017 (APHINITY) | Non-randomized portion of RCT |
Patients in APHINITY had HER2-positive breast cancer. Note that ranges for FAC are given in the protocol, replicated here.
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 500 to 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- TH (Taxol) versus THP (Taxol) or TH (Taxotere) versus THP (Taxotere)
References
- Buzdar AU, Blumenschein GR, Smith TL, Powell KC, Hortobagyi GN, Yap HY, Schell FC, Barnes BC, Ames FC, Martin RG, Hersh EM. Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial. Cancer. 1984 Feb 1;53(3):384-9. link to original article contains verified protocol PubMed
- Update: Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol. 1989 Apr;12(2):123-8. PubMed
- Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. link to original article contains protocol PubMed
- Update: Mackey JR, Martin M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. Epub 2012 Dec 12. link to original article PubMed
- Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. link to original article PubMed
- Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. link to original article PubMed
- Martín M, Ruiz A, Ruiz Borrego M, Barnadas A, González S, Calvo L, Margelí Vila M, Antón A, Rodríguez-Lescure A, Seguí-Palmer MA, Muñoz-Mateu M, Dorca Ribugent J, López-Vega JM, Jara C, Espinosa E, Mendiola Fernández C, Andrés R, Ribelles N, Plazaola A, Sánchez-Rovira P, Salvador Bofill J, Crespo C, Carabantes FJ, Servitja S, Chacón JI, Rodríguez CA, Hernando B, Álvarez I, Carrasco E, Lluch A. Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study. J Clin Oncol. 2013 Jul 10;31(20):2593-9. Epub 2013 Jun 3. link to original article PubMed
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
FEC
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FEC: Fluorouracil, Epirubicin, Cyclophosphamide
CEF: Cyclophosphamide, Epirubicin, Fluorouracil
Regimen #1, 500/100/500 x 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Roché et al. 2006 (FNCLCC PACS 01) | Phase III | See link | See link |
Baselga et al. 2012 (NeoALTTO) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in NeoALTTO all had HER2-positive disease.
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
- FNCLCC PACS 01: Docetaxel
- NeoALTTO: Lapatinib or Lapatinib & Trastuzumab or Trastuzumab, according to initial randomization
Regimen #2, 500/100/500 x 4
Study | Evidence |
---|---|
Kelly et al. 2012 | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery, then weekly paclitaxel x 12 versus XT
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen #3, 500/100/500 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Roché et al. 2006 (FNCLCC PACS 01) | Phase III | FEC-D | Seems to have inferior OS |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen #4, 600/60/600 x 3
Study | Evidence |
---|---|
Joensuu et al. 2006 (FinHer) | Non-randomized portion of RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- HER2-negative: Docetaxel x 3 versus vinorelbine x 3
- HER2-positive: Docetaxel x 3 versus TH x 3 versus vinorelbine x 3 versus VH x 3
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Regimen #5, 600/60/600 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
del Mastro et al. 2016 (GONO-MIG5) | Phase III | EP x 4 | Seems not superior |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen #6, 600/75/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2009 (FinXX) | Phase III | See link | See link |
Preceding treatment
- T (Docetaxel) x 3
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Regimen #7, 600/90/600 x 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2008 (GEICAM 9906) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Treatment followed by 3 weeks of no treatment, then paclitaxel.
Regimen #8, 600/90/600 x 6
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2008 (GEICAM 9906) | Phase III | FEC x 4, then P | Inferior DFS |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Regimen #9, oral cyclophosphamide
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Levine et al. 1998 (NCIC CTG MA5) | Phase III | CMF | Superior RFS |
Coombes et al. 2005 (ICCG HDT trial) | Phase III | FEC x 3, then HDT | Seems not superior |
Preceding treatment
- Surgery
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 60 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 75 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
References
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- Levine MN, Bramwell VH, Pritchard KI, Norris BD, Shepherd LE, Abu-Zahra H, Findlay B, Warr D, Bowman D, Myles J, Arnold A, Vandenberg T, MacKenzie R, Robert J, Ottaway J, Burnell M, Williams CK, Tu D. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1998 Aug;16(8):2651-8. link to original article PubMed
- Update: Levine MN, Pritchard KI, Bramwell VH, Shepherd LE, Tu D, Paul N; National Cancer Institute of Canada Clinical Trials Group. Randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol. 2005 Aug 1;23(22):5166-70. link to original article PubMed
- French Adjuvant Study Group. Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2001 Feb 1;19(3):602-11. link to original article PubMed
- Update: Bonneterre J, Roché H, Kerbrat P, Brémond A, Fumoleau P, Namer M, Goudier MJ, Schraub S, Fargeot P, Chapelle-Marcillac I. Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French Adjuvant Study Group 05 randomized trial. J Clin Oncol. 2005 Apr 20;23(12):2686-93. link to original article PubMed
- Fumoleau P, Kerbrat P, Romestaing P, Fargeot P, Brémond A, Namer M, Schraub S, Goudier MJ, Mihura J, Monnier A, Clavère P, Serin D, Seffert P, Pourny C, Facchini T, Jacquin JP, Sztermer JF, Datchary J, Ramos R, Luporsi E. Randomized trial comparing six versus three cycles of epirubicin-based adjuvant chemotherapy in premenopausal, node-positive breast cancer patients: 10-year follow-up results of the French Adjuvant Study Group 01 trial. J Clin Oncol. 2003 Jan 15;21(2):298-305. link to original article PubMed
- Coombes RC, Howell A, Emson M, Peckitt C, Gallagher C, Bengala C, Tres A, Welch R, Lawton P, Rubens R, Woods E, Haviland J, Vigushin D, Kanfer E, Bliss JM. High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial. Ann Oncol. 2005 May;16(5):726-34. Epub 2005 Apr 7. link to original article PubMed
- Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article contains verified protocol PubMed
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
- Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, Symann M, Kerbrat P, Soulié P, Eichler F, Viens P, Monnier A, Vindevoghel A, Campone M, Goudier MJ, Bonneterre J, Ferrero JM, Martin AL, Genève J, Asselain B. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006 Dec 20;24(36):5664-71. Epub 2006 Nov 20. link to original article PubMed
- Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Cold S, Edlund P, Ewertz M, Jensen BB, Kamby C, Nordenskjold B, Bergh J. Improved outcome from substituting methotrexate with epirubicin: results from a randomised comparison of CMF versus CEF in patients with primary breast cancer. Eur J Cancer. 2007 Mar;43(5):877-84. Epub 2007 Feb 16. link to original article PubMed
- Martín M, Rodríguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E, Alvarez JV, García Puche JL, Sánchez-Rovira P, Gonzalez S, López-Vega JM; GEICAM 9906 Study Investigators. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008 Jun 4;100(11):805-14. Epub 2008 May 27. link to original article contains verified protocol PubMed
- Ellis P, Barrett-Lee P, Johnson L, Cameron D, Wardley A, O'Reilly S, Verrill M, Smith I, Yarnold J, Coleman R, Earl H, Canney P, Twelves C, Poole C, Bloomfield D, Hopwood P, Johnston S, Dowsett M, Bartlett JM, Ellis I, Peckitt C, Hall E, Bliss JM; TACT Trial Management Group; TACT Trialists. Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial. Lancet. 2009 May 16;373(9676):1681-92. link to original article link to PMC article PubMed
- Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Asola R, Kokko R, Ahlgren J, Auvinen P, Hemminki A, Paija O, Helle L, Nuortio L, Villman K, Nilsson G, Lahtela SL, Lehtiö K, Pajunen M, Poikonen P, Nyandoto P, Kataja V, Bono P, Leinonen M, Lindman H; FinXX Study Investigators. Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial. Lancet Oncol. 2009 Dec;10(12):1145-51. Epub 2009 Nov 10. link to original article contains verified protocol PubMed
- Update: Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H. Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol. 2012 Jan 1;30(1):11-8. Epub 2011 Nov 21. link to original article PubMed
- Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M; NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet. 2012 Feb 18;379(9816):633-40. Epub 2012 Jan 17. Erratum in: Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. link to original article link to PMC article contains verified protocol PubMed
- Update: de Azambuja E, Holmes AP, Piccart-Gebhart M, Holmes E, Di Cosimo S, Swaby RF, Untch M, Jackisch C, Lang I, Smith I, Boyle F, Xu B, Barrios CH, Perez EA, Azim HA Jr, Kim SB, Kuemmel S, Huang CS, Vuylsteke P, Hsieh RK, Gorbunova V, Eniu A, Dreosti L, Tavartkiladze N, Gelber RD, Eidtmann H, Baselga J. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014 Sep;15(10):1137-46. Epub 2014 Aug 14. link to original article PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. link to original article PubMed
- Del Mastro L, Levaggi A, Michelotti A, Cavazzini G, Adami F, Scotto T, Piras M, Danese S, Garrone O, Durando A, Accortanzo V, Bighin C, Miglietta L, Pastorino S, Pronzato P, Castiglione F, Landucci E, Conte P, Bruzzi P. 5-Fluorouracil, epirubicin and cyclophosphamide versus epirubicin and paclitaxel in node-positive early breast cancer: a phase-III randomized GONO-MIG5 trial. Breast Cancer Res Treat. 2016 Jan;155(1):117-26. link to original article contains verified protocol PubMed
- Coombes RC, Kilburn LS, Tubiana-Mathieu N, Olmos T, Van Bochove A, Perez-Lopez FR, Palmieri C, Stebbing J, Bliss JM. Epirubicin dose and sequential hormonal therapy-Mature results of the HMFEC randomised phase III trial in premenopausal patients with node positive early breast cancer. Eur J Cancer. 2016 Jun;60:146-53. Epub 2016 Apr 26. link to original article PubMed
- Kerbrat P, Desmoulins I, Roca L, Levy C, Lortholary A, Marre A, Delva R, Rios M, Viens P, Brain É, Serin D, Edel M, Debled M, Campone M, Mourret-Reynier MA, Bachelot T, Foucher-Goudier MJ, Asselain B, Lemonnier J, Martin AL, Roché H. Optimal duration of adjuvant chemotherapy for high-risk node-negative (N-) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106). Eur J Cancer. 2017 Jul;79:166-175. Epub 2017 May 11. link to original article PubMed
- von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I, Levy C, Yardley DA, Bines J, Gelber RD, Piccart M, Baselga J; APHINITY Steering Committee and Investigators. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-131. Epub 2017 Jun 5. link to original article link to supplementary protocol contains verified protocol in supplementary protocol link to PMC article PubMed
Paclitaxel monotherapy
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T: Taxol (Paclitaxel)
P: Paclitaxel
pT: pacliTaxel
Regimen #1, 80 mg/m2 weekly
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Romond et al. 2005 (NSABP B-31) | Phase III | TH | Inferior OS | Might have inferior DASI score |
Romond et al. 2005 (NCCTG N9831) | Phase III | See link | See link | |
Sparano et al. 2008 (ECOG E1199) | Phase III | Paclitaxel q3wk | Superior OS | |
Docetaxel q3wk Docetaxel weekly |
Not reported | |||
Kelly et al. 2012 | Phase III | XT | Seems not superior | |
Shulman et al. 2012 (CALGB 40101) | Phase III | ddAC x 4 | Seems not superior | |
ddAC x 6 | Seems not superior | |||
Weekly paclitaxel x 18 | Seems not superior |
Note: Patients in NSABP B-31 and NCCTG N9831 were HER2-positive. This paclitaxel dosing schedule was an option after 2003 in NSABP B-31, and was used for all patients in NCCTG N9831. In CALGB 40101, this is the dosing before a mid-protocol amendment in 2003. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- NSABP B-31, NCCTG N9831, ECOG E1199, CALGB 40101: AC x 4
- Kelly et al. 2012: Surgery
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per week
12-week course
Subsequent treatment
- Kelly et al. 2012: FEC x 4
Regimen #2, 100 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martín et al. 2008 (GEICAM 9906) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- FEC x 4
Chemotherapy
- Paclitaxel (Taxol) 100 mg/m2 IV once per week
8 week course
Regimen #3, 175 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Henderson et al. 2003 (INT 0148/CALGB 9344) | Phase III | Observation | Superior OS |
Citron et al. 2003 (CALGB 9741) | Non-randomized portion of RCT | ||
Romond et al. 2005 (NSABP B-31) | Phase III | TH | Inferior OS |
Sparano et al. 2008 (ECOG E1199) | Phase III | Paclitaxel weekly | Inferior OS |
Docetaxel q3wk | Seems to have inferior DFS | ||
Docetaxel weekly | Seems not superior | ||
Earl et al. 2017 (tAnGo) | Phase III | TG | Seems not superior |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Patients in NSABP B-31 were HER2-positive.
Preceding treatment
- INT 0148/CALGB 9344: AC x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
- CALGB 9741, NSABP B-31, and ECOG E1199: AC x 4
- tAnGo: EC x 4
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
21-day cycle for 4 cycles
Regimen #4, 225 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mamounas et al. 2005 (NSABP B-28) | Phase III | Observation | Superior PFS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- AC x 4
Chemotherapy
- Paclitaxel (Taxol) 225 mg/m2 IV over 3 hours once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- NCCTG N9831: H
References
- Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. link to original article contains verified protocol PubMed
- Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, Davidson NE, Martino S, Livingston R, Ingle JN, Perez EA, Carpenter J, Hurd D, Holland JF, Smith BL, Sartor CI, Leung EH, Abrams J, Schilsky RL, Muss HB, Norton L. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9. Epub 2003 Feb 13. link to original article contains verified protocol PubMed
- Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article PubMed
- Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. link to original article PubMed
- Update: Perez EA, Suman VJ, Davidson NE, Gralow JR, Kaufman PA, Visscher DW, Chen B, Ingle JN, Dakhil SR, Zujewski J, Moreno-Aspitia A, Pisansky TM, Jenkins RB. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4491-7. Epub 2011 Oct 31. link to original article link to PMC article PubMed
- Update: Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G, Davidson NE, Mamounas E, Zujewski JA, Wolmark N. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52. link to original article link to PMC article PubMed
- Update and HRQoL analysis: Ganz PA, Romond EH, Cecchini RS, Rastogi P, Geyer CE Jr, Swain SM, Jeong JH, Fehrenbacher L, Gross HM, Brufsky AM, Flynn PJ, Wahl TA, Seay TE, Wade JL 3rd, Biggs DD, Atkins JN, Polikoff J, Zapas JL, Mamounas EP, Wolmark N. Long-term follow-up of cardiac function and quality of life for patients in NSABP protocol B-31/NRG Oncology: a randomized trial comparing the safety and efficacy of doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel and trastuzumab in patients with node-positive breast cancer with tumors overexpressing human epidermal growth factor receptor 2. J Clin Oncol. 2017 Dec 10;35(35):3942-3948. Epub 2017 Oct 26. link to original article link to PMC article PubMed
- Sparano JA, Wang M, Martino S, Jones V, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71. link to original article link to PMC article PubMed
- Update: Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, Wolff AC, Sledge GW Jr, Wood WC, Davidson NE. Long-term follow-up of the E1199 phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015 Jul 20;33(21):2353-60. Epub 2015 Jun 15. link to original article link to PMC article PubMed
- Martín M, Rodríguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Munárriz B, Rodríguez CA, Crespo C, de Alava E, López García-Asenjo JA, Guitián MD, Almenar S, González-Palacios JF, Vera F, Palacios J, Ramos M, Gracia Marco JM, Lluch A, Alvarez I, Seguí MA, Mayordomo JI, Antón A, Baena JM, Plazaola A, Modolell A, Pelegrí A, Mel JR, Aranda E, Adrover E, Alvarez JV, García Puche JL, Sánchez-Rovira P, Gonzalez S, López-Vega JM; GEICAM 9906 Study Investigators. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008 Jun 4;100(11):805-14. Epub 2008 May 27. link to original article contains verified protocol PubMed
- Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU. Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol. 2012 Mar 20;30(9):930-5. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- Shulman LN, Cirrincione CT, Berry DA, Becker HP, Perez EA, O'Regan R, Martino S, Atkins JN, Mayer E, Schneider CJ, Kimmick G, Norton L, Muss H, Winer EP, Hudis C. Six cycles of doxorubicin and cyclophosphamide or paclitaxel are not superior to four cycles as adjuvant chemotherapy for breast cancer in women with zero to three positive axillary nodes: Cancer and Leukemia Group B 40101. J Clin Oncol. 2012 Nov 20;30(33):4071-6. Epub 2012 Jul 23. link to original article contains verified protocol link to study protocol PDF link to PMC article PubMed
- Update: Shulman LN, Berry DA, Cirrincione CT, Becker HP, Perez EA, O'Regan R, Martino S, Shapiro CL, Schneider CJ, Kimmick G, Burstein HJ, Norton L, Muss H, Hudis CA, Winer EP. Comparison of doxorubicin and cyclophosphamide versus single-agent paclitaxel as adjuvant therapy for breast cancer in women with 0 to 3 positive axillary nodes: CALGB 40101 (Alliance). J Clin Oncol. 2014 Aug 1;32(22):2311-7. link to PMC article PubMed
- Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nisticò C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. Epub 2015 Mar 2. link to original article PubMed
- Watanabe T, Kuranami M, Inoue K, Masuda N, Aogi K, Ohno S, Iwata H, Mukai H, Uemura Y, Ohashi Y. Comparison of an AC-taxane versus AC-free regimen and paclitaxel versus docetaxel in patients with lymph node-positive breast cancer: Final results of the National Surgical Adjuvant Study of Breast Cancer 02 trial, a randomized comparative phase 3 study. Cancer. 2017 Mar 1;123(5):759-768. Epub 2017 Jan 12. link to original article PubMed
- Earl HM, Hiller L, Howard HC, Dunn JA, Young J, Bowden SJ, McDermaid M, Waterhouse AK, Wilson G, Agrawal R, O'Reilly S, Bowman A, Ritchie DM, Goodman A, Hickish T, McAdam K, Cameron D, Dodwell D, Rea DW, Caldas C, Provenzano E, Abraham JE, Canney P, Crown JP, Kennedy MJ, Coleman R, Leonard RC, Carmichael JA, Wardley AM, Poole CJ; tAnGo trial collaborators. Addition of gemcitabine to paclitaxel, epirubicin, and cyclophosphamide adjuvant chemotherapy for women with early-stage breast cancer (tAnGo): final 10-year follow-up of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Jun;18(6):755-769. Epub 2017 May 4. link to original article contains protocol PubMed
TAC (Taxotere)
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TAC: Taxotere (Docetaxel), Adriamycin (Doxorubicin), Cyclophosphamide
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Martin et al. 2005 (BCIRG 001) | Phase III | FAC | Superior OS |
Martín et al. 2010 (GEICAM 9805) | Phase III | FAC | Superior DFS |
Eiermann et al. 2011 (BCIRG-005) | Phase III | AC, then T | Seems not superior |
Swain et al. 2013 (NSABP B-38) | Phase III | ddAC, then ddP | Seems not superior |
ddAC, then ddPG | Seems not superior | ||
Blum et al. 2017 (USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49) | Phase III | TC | Seems to have superior IDFS |
Note: Blum et al. 2017 is a pooled analysis of three RCTs, some of which had arms other than TAC and TC. Refer to the paper for further details.
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, administered third, one hour after cyclophosphamide
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 15 minutes once on day 1, administered first
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV over 1 to 5 minutes once on day 1, administered second
Supportive medications
- Dexamethasone (Decadron) 8 mg PO every 12 hours x 6 total doses, starting the day before treatment
- Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 14 of every cycle (prophylaxis)
- G-CSF not originally routinely administered unless patients had febrile neutropenia, but some guidelines recommend one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 4 to 11
- Lenograstim (Granocyte) 150 mcg/m2 SC once per day on days 4 to 11
21-day cycle for 6 cycles
References
- Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, Tomiak E, Al-Tweigeri T, Chap L, Juhos E, Guevin R, Howell A, Fornander T, Hainsworth J, Coleman R, Vinholes J, Modiano M, Pinter T, Tang SC, Colwell B, Prady C, Provencher L, Walde D, Rodriguez-Lescure A, Hugh J, Loret C, Rupin M, Blitz S, Jacobs P, Murawsky M, Riva A, Vogel C; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13. link to original article contains protocol PubMed
- Update: Mackey JR, Martin M, Pienkowski T, Rolski J, Guastalla JP, Sami A, Glaspy J, Juhos E, Wardley A, Fornander T, Hainsworth J, Coleman R, Modiano MR, Vinholes J, Pinter T, Rodríguez-Lescure A, Colwell B, Whitlock P, Provencher L, Laing K, Walde D, Price C, Hugh JC, Childs BH, Bassi K, Lindsay MA, Wilson V, Rupin M, Houé V, Vogel C; TRIO/BCIRG 001 investigators. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013 Jan;14(1):72-80. Epub 2012 Dec 12. link to original article PubMed
- Martín M, Seguí MA, Antón A, Ruiz A, Ramos M, Adrover E, Aranda I, Rodríguez-Lescure A, Grosse R, Calvo L, Barnadas A, Isla D, Martinez del Prado P, Ruiz Borrego M, Zaluski J, Arcusa A, Muñoz M, López Vega JM, Mel JR, Munarriz B, Llorca C, Jara C, Alba E, Florián J, Li J, López García-Asenjo JA, Sáez A, Rios MJ, Almenar S, Peiró G, Lluch A; GEICAM 9805 Investigators. Adjuvant docetaxel for high-risk, node-negative breast cancer. N Engl J Med. 2010 Dec 2;363(23):2200-10. link to original article PubMed
- Eiermann W, Pienkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press M, Sauter G, Lindsay MA, Riva A, Buyse M, Drevot P, Taupin H, Mackey JR. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84. Epub 2011 Sep 12. link to original article contains verified protocol PubMed
- Update: Mackey JR, Pieńkowski T, Crown J, Sadeghi S, Martin M, Chan A, Saleh M, Sehdev S, Provencher L, Semiglazov V, Press MF, Sauter G, Lindsay M, Houé V, Buyse M, Drevot P, Hitier S, Bensfia S, Eiermann W; Translational Research In Oncology (TRIO)/ Breast Cancer International Research Group (BCIRG)-005 investigators. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann Oncol. 2016 Jun;27(6):1041-7. Epub 2016 Mar 2. link to original article PubMed
- Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, Fehrenbacher L, Azar CA, Robidoux A, Polikoff JA, Brufsky AM, Biggs DD, Levine EA, Zapas JL, Provencher L, Northfelt DW, Paik S, Costantino JP, Mamounas EP, Wolmark N. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013 Sep 10;31(26):3197-204. Epub 2013 Aug 12. link to original article link to PMC article contains verified protocol PubMed
- Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. link to original article link to PMC article contains verified protocol PubMed
TC (Taxotere)
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TC: Taxotere (Docetaxel), Cyclophosphamide
Regimen #1, 4 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jones et al. 2006 (US Oncology Trial 9735) | Phase III | AC | Seems to have superior OS |
Blum et al. 2017 (USOR 06-090; NSABP-46-I/USOR 07132; NSABP B-49) | Phase III | TAC | Seems to have inferior IDFS |
Note: Blum et al. 2017 is a pooled analysis of three RCTs, some of which had arms other than TAC and TC. Refer to the paper for further details.
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
Supportive medications
- All cycles given with Filgrastim (Neupogen) support
21-day cycle for 4 cycles
Regimen #2, 6 cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mavroudis et al. 2016 (HORG CT/07.17) | Phase III | ddFEC, then D | Inconclusive whether non-inferior |
Preceding treatment
- Surgery
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for 6 cycles
References
- Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. Erratum in: J Clin Oncol. 2007 May 1;25(13):1819. link to original article PubMed
- Update: Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, Pippen JE, Bordelon JH, Kirby RL, Sandbach J, Hyman WJ, Richards DA, Mennel RG, Boehm KA, Meyer WG, Asmar L, Mackey D, Riedel S, Muss H, Savin MA. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83. Epub 2009 Feb 9. link to original article PubMed
- Mavroudis D, Matikas A, Malamos N, Papakotoulas P, Kakolyris S, Boukovinas I, Athanasiadis A, Kentepozidis N, Ziras N, Katsaounis P, Saloustros E, Georgoulias V; Breast Cancer Investigators of the Hellenic Oncology Research Group (HORG), Athens, Greece. Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG). Ann Oncol. 2016 Oct;27(10):1873-8. Epub 2016 Aug 8. link to original article contains verified protocol PubMed
- Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA, Robert NJ, Hopkins JO, O'Shaughnessy JA, Dang CT, Gómez HL, Fehrenbacher L, Vukelja SJ, Lyss AP, Paul D, Brufsky AM, Jeong JH, Colangelo LH, Swain SM, Mamounas EP, Jones SE, Wolmark N. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-2655. Epub 2017 Apr 11. link to original article link to PMC article contains verified protocol PubMed
Vinorelbine monotherapy
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V: Vinorelbine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Joensuu et al. 2006 (FinHer) | Phase III | Docetaxel | Inferior DDFS |
TH (Taxotere) VH |
Seems not superior |
Patients without HER2/neu amplification were only randomized to this arm verus the docetaxel arm.
Preceding treatment
- Surgery
Chemotherapy
- Vinorelbine (Navelbine) as follows:
- Cycles 1 & 2: 25 mg/m2 IV over 5 to 10 minutes once per day on days 1, 8, 15
- Cycle 3: 25 mg/m2 IV over 5 to 10 minutes once per day on days 1 & 8
21-day cycle for 3 cycles
Subsequent treatment
References
- Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkiö S, Flander M, Helle L, Ingalsuo S, Johansson K, Jääskeläinen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. link to original article contains verified protocol PubMed
- Update: Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL. Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009 Dec 1;27(34):5685-92. link to original article PubMed
Adjuvant endocrine therapy
Anastrozole monotherapy
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Regimen #1, 3-year course
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Kaufmann et al. 2007 (ARNO 95) | Phase III | See link | See link | |
Dubsky et al. 2012 (ABCSG-8) | Phase III | See link | See link | |
Tjan-Heijnen et al. 2017 (DATA) | Phase III | 6 y of anastrozole | Might have inferior DFS | Less toxic |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
3-year course
Regimen #2, 5-year course
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Howell et al. 2005 (ATAC) | Phase III | Anastrozole & Tamoxifen | Not reported |
Tamoxifen | Seems to have superior DFS | ||
Goss et al. 2013 (NCIC CTG MA.27) | Phase III | Exemestane | Seems not superior |
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
5-year course of therapy
Regimen #3, 6-year course
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Tjan-Heijnen et al. 2017 (DATA) | Phase III | 3 y of anastrozole | Might have superior DFS | More toxic |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Tamoxifen x 2-3 y
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
6-year course
References
- Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. link to original article PubMed
- Update: Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. link to original article PubMed
- Update: Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. link to original article PubMed
- Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. link to original article PubMed
- Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. link to original article PubMed
- Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. Epub 2013 Jan 28. link to original article contains verified protocol link to PMC article PubMed
- Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, Swinkels ACP, Smorenburg CH, van der Sangen MJC, Kroep JR, De Graaf H, Honkoop AH, Erdkamp FLG, van den Berkmortel FWPJ, de Boer M, de Roos WK, Linn SC, Imholz ALT, Seynaeve CM; Dutch Breast Cancer Research Group (BOOG) for the DATA Investigators. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1502-1511. Epub 2017 Oct 12. Erratum in: Lancet Oncol. 2017 Nov;18(11):e642. link to original article contains verified protocol PubMed
Exemestane monotherapy
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Regimen #1, 2- to 3-year course
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 2004 (IES) | Phase III | See link | See link |
van de Velde et al. 2011 (TEAM) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. The IES gave a range of 2 to 3 years of therapy. TEAM gave a range of 2 to 2.5 years of therapy.
Preceding treatment
- Tamoxifen x 2-3y
Endocrine therapy
- Exemestane (Aromasin) 25 mg PO once per day
2 to 3 years to complete a 5-year course
Regimen #2, 5 years
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Mamounas et al. 2008 (NSABP B-33) | Phase III | Placebo | Superior RFS |
Goss et al. 2013 (NCIC CTG MA.27) | Phase III | Anastrozole | Seems not superior |
Preceding treatment
- NSABP B-33: Tamoxifen x 5y
Endocrine therapy
- Exemestane (Aromasin) 25 mg PO once per day
5-year course of therapy
Regimen #3, 5 years, with OFS
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pagani et al. 2014 (TEXT/SOFT) | Phase III | Tamoxifen | Superior DFS |
Tamoxifen & OFS | Superior DFS |
OFS: Ovarian Function Suppression These regimens are intended for premenopausal patients. Pagani et al. 2014 report on two trials, but only SOFT had the tamoxifen only arm.
Endocrine therapy
- Exemestane (Aromasin) 25 mg PO once per day
- Ovarian Suppression as follows:
- TEXT: Triptorelin (Trelstar LA) 3.75 mg IM every 28 days
- "Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin."
- SOFT: Choice of mechanism left to investigators
- TEXT: Triptorelin (Trelstar LA) 3.75 mg IM every 28 days
5 years of therapy
References
- Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. link to original article PubMed
- Update: Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. link to original article PubMed
- Update: Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. link to original article PubMed
- Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. link to original article PubMed
- van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. link to original article contains verified protocol PubMed
- Update: Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. link to original article PubMed
- Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. Epub 2013 Jan 28. link to original article contains verified protocol link to PMC article PubMed
- Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. link to original article contains verified protocol link to PMC article PubMed
Letrozole monotherapy
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Regimen #1, 2 years of therapy
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Breast International Group (BIG) 1-98 Collaborative Group 2006 | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
2-year course
Treatment followed by tamoxifen.
Regimen #2, 3 years of therapy
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Breast International Group (BIG) 1-98 Collaborative Group 2006 | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Tamoxifen x 2y
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
3-year course
Regimen #3, 5 years of therapy
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Goss et al. 2003 (NCIC CTG MA.17) | Phase III | Placebo | Superior DFS | No clinical difference in QoL |
Breast International Group (BIG) 1-98 Collaborative Group 2006 | Phase III | Letrozole, then Tamoxifen | Seems not superior (*) | |
Tamoxifen | Superior OS (*) | |||
Tamoxifen, then Letrozole | Seems not superior (*) | |||
Goss et al. 2016 (NCIC CTG MA.17R) | Phase III | Letrozole x 10y | Inferior DFS | No clinical difference in QoL |
Efficacy reported for BIG 1-98 based on the 2011 update.
Preceding treatment
- NCIC CTG MA.17: Most patients received 5 years of tamoxifen therapy prior to starting letrozole
- NCIC CTG MA.17R: Letrozole for 5 years
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
5-year course of therapy
Regimen #4, 10 years of therapy
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Goss et al. 2016 (NCIC CTG MA.17R) | Phase III | Letrozole x 5y | Superior DFS | No clinical difference in QoL |
Continuation of treatment was started within 2 years of the completion of the first 5 years of treatment.
Preceding treatment
- Letrozole for 5 years
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
5 additional years for a total 10-year course of therapy
References
- Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. link to original article PubMed
- Update: Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. link to original article PubMed
- QoL analysis: Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005 Oct 1;23(28):6931-40. Epub 2005 Sep 12. link to original article PubMed
- Update: Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. link to original article PubMed
- Subgroup analysis: Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. link to original article PubMed
- Update: Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. link to original article link to PMC article PubMed
- Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. link to original article PubMed
- Update: Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. link to original article PubMed
- Subgroup analysis: Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. link to original article PubMed
- Subgroup analysis: Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. link to original article PubMed
- Update: Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. link to original article link to PMC article PubMed
- Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. link to original article PubMed
- Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D, Parulekar WR. Extending aromatase-inhibitor adjuvant therapy to 10 Years. N Engl J Med. 2016 Jul 21;375(3):209-19. Epub 2016 Jun 5. link to original article link to PMC article contains verified protocol PubMed
- QoL analysis: Lemieux J, Brundage MD, Parulekar WR, Goss PE, Ingle JN, Pritchard KI, Celano P, Muss H, Gralow J, Strasser-Weippl K, Whelan K, Tu D, Whelan TJ. Quality of life from Canadian Cancer Trials Group MA.17R: a randomized trial of extending adjuvant letrozole to 10 years. J Clin Oncol. 2018 Feb 20;36(6):563-571. Epub 2018 Jan 12. link to original article PubMed
- Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Putter H, van den Bosch J, Maartense E, van Leeuwen-Stok AE, Liefers GJ, Nortier JWR, Rutgers EJT, van de Velde CJH; IDEAL Study Group. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst. 2018 Jan 1;110(1). Epub 2017 Aug 23. link to original article PubMed
Leuprolide monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schmid et al. 2007 (TABLE) | Phase III | CMF | Superior OS |
Endocrine therapy
- Leuprolide (Lupron) 3-month depot 11.25 mg SC
Every 3 months x 2 years
References
- Schmid P, Untch M, Kossé V, Bondar G, Vassiljev L, Tarutinov V, Lehmann U, Maubach L, Meurer J, Wallwiener D, Possinger K. Leuprorelin acetate every-3-months depot versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant treatment in premenopausal patients with node-positive breast cancer: the TABLE study. J Clin Oncol. 2007 Jun 20;25(18):2509-15. link to original article contains verified protocol PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Rydén et al. 2005 (SBII:2pre) | Phase III | Tamoxifen | Inferior RFS |
Hutchins et al. 2005 (INT-0102) | Phase III | Tamoxifen | Seems not superior |
No further treatment. Used as a comparator arm.
Preceding treatment
References
- Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. link to original article PubMed
- Update: Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. link to original article PubMed
- Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. link to original article PubMed
- Zdenkowski N, Forbes JF, Boyle FM, Kannourakis G, Gill PG, Bayliss E, Saunders C, Della-Fiorentina S, Kling N, Campbell I, Mann GB, Coates AS, Gebski V, Davies L, Thornton R, Reaby L, Cuzick J, Green M; Australia and New Zealand Breast Cancer Trials Group. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016 May;27(5):806-12. Epub 2016 Feb 9. link to original article PubMed
- Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen breast cancer trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. link to original article PubMed
Placebo
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fisher et al. 2001 (NSABP B-23) | Phase III | Tamoxifen | Seems not superior |
Goss et al. 2003 (NCIC CTG MA.17) | Phase III | Letrozole | Inferior DFS |
Mamounas et al. 2008 (NSABP B-33) | Phase III | Exemestane | Inferior RFS |
No active treatment. Used as a comparator arm.
Preceding treatment
References
- Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
- Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003 Nov 6;349(19):1793-802. Epub 2003 Oct 9. link to original article PubMed
- Update: Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71. link to original article PubMed
- QoL analysis: Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005 Oct 1;23(28):6931-40. Epub 2005 Sep 12. link to original article PubMed
- Update: Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. J Clin Oncol. 2008 Apr 20;26(12):1956-64. Epub 2008 Mar 10. link to original article PubMed
- Subgroup analysis: Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Tu D. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008 Apr 20;26(12):1948-55. Epub 2008 Mar 10. link to original article PubMed
- Update: Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012 Mar 1;30(7):718-21. Epub 2011 Oct 31. link to original article link to PMC article PubMed
- Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. link to original article PubMed
Tamoxifen monotherapy
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Regimen #1, 1 year
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ejlertsen et al. 2013 (DBCG 82C) | Phase III | CMFT | Inferior DFS |
Tamoxifen & RT | Not reported |
Endocrine therapy
- Tamoxifen (Nolvadex) 30 mg PO once per day
1 year of therapy
Regimen #2, 2 years
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Coombes et al. 2004 (IES) | Phase III | See link | See link |
Breast International Group (BIG) 1-98 Collaborative Group 2006 | Phase III | See link | See link |
Kaufmann et al. 2007 (ARNO 95) | Phase III | See link | See link |
Dubsky et al. 2012 (ABCSG-8) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. IES gave a range of 2 to 3 years of therapy.
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
2-year course
Subsequent treatment
- IES: Exemestane
- BIG 1-98: Letrozole
- ABCSG-8 & ARNO 95: Anastrozole x 3 y
Regimen #3, 3 years
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Breast International Group (BIG) 1-98 Collaborative Group 2006 | Phase III | See link | See link |
van de Velde et al. 2011 (TEAM) | Phase III | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. TEAM gave a range of 2.5 to 3 years of therapy.
Preceding treatment
- BIG 1-98: Letrozole x 2y
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
3-year course
Subsequent treatment
- TEAM: Exemestane
Regimen #4, 5 years
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fisher et al. 2001 (NSABP B-23) | Phase III | Placebo | Seems not superior |
Assikis et al. 2003 | Phase III | FAC, then MV | Seems not superior |
Coombes et al. 2004 (IES) | Phase III | Tamoxifen x 2-3y, then Exemestane x 2-3y | Seems to have inferior OS (*) |
Hutchins et al. 2005 (INT-0102) | Phase III | Observation | Seems not superior |
Breast International Group (BIG) 1-98 Collaborative Group 2006 | Phase III | Letrozole | Inferior OS (*) |
Letrozole x 2y, then Tamoxifen x 3y | Not reported | ||
Tamoxifen x 2y, then Letrozole x 3y | Not reported | ||
Kaufmann et al. 2007 (ARNO 95) | Phase III | Tamoxifen x 2y, then Anastrozole x 3y | Seems to have inferior OS |
Mamounas et al. 2008 (NSABP B-33) | Non-randomized portion of RCT | ||
van de Velde et al. 2011 (TEAM) | Phase III | Tamoxifen x 2.5-3y, then Exemestane x 2-2.5y | Seems not superior |
Pritchard et al. 2011 (NCIC CTG MA.14) | Phase III | Tamoxifen & Octreotide LAR | Seems not superior |
Dubsky et al. 2012 (ABCSG-8) | Phase III | Tamoxifen x 2y, then Anastrozole x 3y | Might have inferior RFS |
Davies et al. 2013 (ATLAS) | Phase III | Tamoxifen x 10 years | Inferior OS |
Pagani et al. 2014 (SOFT) | Phase III | Exemestane & OFS | Inferior DFS |
Tamoxifen & OFS | Might have inferior DFS (*) |
Note: Pagani et al. 2014 reports on two trials, but only SOFT had the tamoxifen only arm; efficacy for this arm is as reported in Francis et al. 2015. Efficacy for BIG 1-98 and IES is based on the 2011 updates.
Preceding treatment
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
5 years of therapy
Subsequent treatment
- NSABP B-33: Exemestane versus Placebo
Regimen #5, 5 years, with OFS
OFS: Ovarian Function Suppression
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pagani et al. 2014 (TEXT/SOFT) | Phase III | Exemestane & OFS | Inferior DFS |
Tamoxifen | Might have superior DFS (*) |
These regimens are intended for premenopausal patients. Pagani et al. 2014 reports on two trials, but only SOFT had the tamoxifen only arm; efficacy for this arm is as reported in Francis et al. 2015.
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
- Ovarian Suppression as follows:
- TEXT: Triptorelin (Trelstar LA) 3.75 mg IM every 28 days
- "Bilateral oophorectomy or ovarian irradiation was allowed after at least 6 months of triptorelin."
- SOFT: Choice of mechanism left to investigators
- TEXT: Triptorelin (Trelstar LA) 3.75 mg IM every 28 days
5 years of therapy
Regimen #6, 10 years
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Davies et al. 2013 (ATLAS) | Phase III | Tamoxifen x 5 years | Superior OS |
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
10 years of therapy
References
- Review: Jaiyesimi IA, Buzdar AU, Decker DA, Hortobagyi GN. Use of tamoxifen for breast cancer: twenty-eight years later. J Clin Oncol. 1995 Feb;13(2):513-29. link to original article PubMed
- Preliminary results from the cancer research campaign trial evaluating tamoxifen duration in women aged fifty years or older with breast cancer. Current Trials working Party of the Cancer Research Campaign Breast Cancer Trials Group. J Natl Cancer Inst. 1996 Dec 18;88(24):1834-9. Erratum in: J Natl Cancer Inst 1997 Apr 16;89(8):590. PubMed
- Update: Hackshaw A, Roughton M, Forsyth S, Monson K, Reczko K, Sainsbury R, Baum M. Long-term benefits of 5 years of tamoxifen: 10-year follow-up of a large randomized trial in women at least 50 years of age with early breast cancer. J Clin Oncol. 2011 May 1;29(13):1657-63. Epub 2011 Mar 21. link to original article PubMed
- NSABP B-23: Fisher B, Anderson S, Tan-Chiu E, Wolmark N, Wickerham DL, Fisher ER, Dimitrov NV, Atkins JN, Abramson N, Merajver S, Romond EH, Kardinal CG, Shibata HR, Margolese RG, Farrar WB. Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol. 2001 Feb 15;19(4):931-42. link to original article PubMed
- Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. link to original article contains protocol PubMed
- IES: Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM, van de Velde C; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92. link to original article PubMed
- Update: Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, Jassem J, Van de Velde CJ, Delozier T, Alvarez I, Del Mastro L, Ortmann O, Diedrich K, Coates AS, Bajetta E, Holmberg SB, Dodwell D, Mickiewicz E, Andersen J, Lønning PE, Cocconi G, Forbes J, Castiglione M, Stuart N, Stewart A, Fallowfield LJ, Bertelli G, Hall E, Bogle RG, Carpentieri M, Colajori E, Subar M, Ireland E, Bliss JM; Intergroup Exemestane Study. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70. link to original article PubMed
- Update: Bliss JM, Kilburn LS, Coleman RE, Forbes JF, Coates AS, Jones SE, Jassem J, Delozier T, Andersen J, Paridaens R, van de Velde CJ, Lønning PE, Morden J, Reise J, Cisar L, Menschik T, Coombes RC. Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J Clin Oncol. 2012 Mar 1;30(7):709-17. Epub 2011 Oct 31. link to original article PubMed
- CALGB 9343: Hughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L; Cancer and Leukemia Group B; Radiation Therapy Oncology Group; Eastern Cooperative Oncology Group. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):971-7. link to original article link to original article PubMed
- Update: Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013 Jul 1;31(19):2382-7. Epub 2013 May 20. link to PMC article PubMed
- ATAC: Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS; ATAC Trialists' Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2. link to original article PubMed
- Update: Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group, Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53. link to original article PubMed
- Update: Cuzick J, Sestak I, Baum M, Buzdar A, Howell A, Dowsett M, Forbes JF; ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 2010 Dec;11(12):1135-41. link to original article PubMed
- Rydén L, Jönsson PE, Chebil G, Dufmats M, Fernö M, Jirström K, Källström AC, Landberg G, Stål O, Thorstenson S, Nordenskjöld B; South Swedish Breast Cancer Group; South-East Swedish Breast Cancer Group. Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up. Eur J Cancer. 2005 Jan;41(2):256-64. link to original article PubMed
- Update: Ekholm M, Bendahl PO, Fernö M, Nordenskjöld B, Stål O, Rydén L. Two years of adjuvant tamoxifen provides a survival benefit compared with no systemic treatment in premenopausal patients with primary breast cancer: Long-term follow-up (> 25 years) of the phase III SBII:2pre trial. J Clin Oncol. 2016 Jul 1;34(19):2232-8. Epub 2016 May 9. link to original article PubMed
- Review: Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. link to original article PubMed
- INT-0102: Hutchins LF, Green SJ, Ravdin PM, Lew D, Martino S, Abeloff M, Lyss AP, Allred C, Rivkin SE, Osborne CK. Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102. J Clin Oncol. 2005 Nov 20;23(33):8313-21. link to original article PubMed
- BIG 1-98: Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, Coates AS, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Rabaglio M, Smith I, Wardley A, Price KN, Goldhirsch A. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005 Dec 29;353(26):2747-57. Erratum in: N Engl J Med. 2006 May 18;354(20):2200. Wardly, Andrew [corrected to Wardley, Andrew ]. link to original article PubMed
- Update: Coates AS, Keshaviah A, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens R, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Smith I, Chirgwin J, Nogaret JM, Pienkowski T, Wardley A, Jakobsen EH, Price KN, Goldhirsch A. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92. Epub 2007 Jan 2. link to original article PubMed
- Subgroup analysis: Rasmussen BB, Regan MM, Lykkesfeldt AE, Dell'Orto P, Del Curto B, Henriksen KL, Mastropasqua MG, Price KN, Méry E, Lacroix-Triki M, Braye S, Altermatt HJ, Gelber RD, Castiglione-Gertsch M, Goldhirsch A, Gusterson BA, Thürlimann B, Coates AS, Viale G; BIG 1-98 Collaborative and International Breast Cancer Study Groups. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial. Lancet Oncol. 2008 Jan;9(1):23-8. Epub 2007 Dec 20. link to original article PubMed
- Subgroup analysis: Crivellari D, Sun Z, Coates AS, Price KN, Thürlimann B, Mouridsen H, Mauriac L, Forbes JF, Paridaens RJ, Castiglione-Gertsch M, Gelber RD, Colleoni M, Láng I, Del Mastro L, Gladieff L, Rabaglio M, Smith IE, Chirgwin JH, Goldhirsch A. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial. J Clin Oncol. 2008 Apr 20;26(12):1972-9. Epub 2008 Mar 10. link to original article PubMed
- Update: Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, Forbes JF, Smith I, Láng I, Wardley A, Rabaglio M, Price KN, Gelber RD, Coates AS, Thürlimann B; BIG 1-98 Collaborative Group.; International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol. 2011 Nov;12(12):1101-8. link to original article link to PMC article PubMed
- ARNO 95: Kaufmann M, Jonat W, Hilfrich J, Eidtmann H, Gademann G, Zuna I, von Minckwitz G. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 Study. J Clin Oncol. 2007 Jul 1;25(19):2664-70. Epub 2007 Jun 11. link to original article PubMed
- NSABP B-33: Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, Eisen A, Fehrenbacher L, Farrar WB, Atkins JN, Pajon ER, Vogel VG, Kroener JF, Hutchins LF, Robidoux A, Hoehn JL, Ingle JN, Geyer CE Jr, Costantino JP, Wolmark N. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008 Apr 20;26(12):1965-71. Epub 2008 Mar 10. link to original article PubMed
- TEAM: van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, Paridaens R, Markopoulos C, Hozumi Y, Hille ET, Kieback DG, Asmar L, Smeets J, Nortier JW, Hadji P, Bartlett JM, Jones SE. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011 Jan 22;377(9762):321-31. link to original article contains verified protocol PubMed
- Update: Derks MGM, Blok EJ, Seynaeve C, Nortier JWR, Kranenbarg EM, Liefers GJ, Putter H, Kroep JR, Rea D, Hasenburg A, Markopoulos C, Paridaens R, Smeets JBE, Dirix LY, van de Velde CJH. Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1211-1220. Epub 2017 Jul 18. link to original article PubMed
- NCIC CTG MA.14: Pritchard KI, Shepherd LE, Chapman JA, Norris BD, Cantin J, Goss PE, Dent SF, Walde D, Vandenberg TA, Findlay B, O'Reilly SE, Wilson CF, Han L, Piura E, Whelan TJ, Pollak MN. Randomized trial of tamoxifen versus combined tamoxifen and octreotide LAR Therapy in the adjuvant treatment of early-stage breast cancer in postmenopausal women: NCIC CTG MA.14. J Clin Oncol. 2011 Oct 10;29(29):3869-76. Epub 2011 Sep 12. link to original article PubMed
- Update: Chapman JA, Costantino JP, Dong B, Margolese RG, Pritchard KI, Shepherd LE, Gelmon KA, Wolmark N, Pollak MN. Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29. Breast Cancer Res Treat. 2015 Sep;153(2):353-60. Epub 2015 Aug 15. link to original article link to PMC article PubMed
- ABCSG-8:' Dubsky PC, Jakesz R, Mlineritsch B, Pöstlberger S, Samonigg H, Kwasny W, Tausch C, Stöger H, Haider K, Fitzal F, Singer CF, Stierer M, Sevelda P, Luschin-Ebengreuth G, Taucher S, Rudas M, Bartsch R, Steger GG, Greil R, Filipcic L, Gnant M. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 2012 Mar 1;30(7):722-8. Epub 2012 Jan 23. link to original article PubMed
- ATLAS: Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. Erratum in: Lancet. 2013 Mar 9;381(9869):804. link to original article contains verified protocol link to PMC article PubMed
- DBCG 82C: Ejlertsen B, Jensen MB, Elversang J, Rasmussen BB, Andersson M, Andersen J, Nielsen DL, Cold S, Mouridsen HT. One year of adjuvant tamoxifen compared with chemotherapy and tamoxifen in postmenopausal patients with stage II breast cancer. Eur J Cancer. 2013 Sep;49(14):2986-94. Epub 2013 Jun 8. link to original article contains verified protocol PubMed
- TEXT/SOFT: Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18. Epub 2014 Jun 1. link to original article contains verified protocol link to PMC article PubMed
- Update: Francis PA, Regan MM, Fleming GF, Láng I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD; SOFT Investigators; International Breast Cancer Study Group. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015 Jan 29;372(5):436-46. Epub 2014 Dec 11. link to original article link to PMC article PubMed
- Jensen MB, Krarup JF, Palshof T, Mouridsen HT, Ejlertsen B. Two years of tamoxifen or no adjuvant systemic therapy for patients with high-risk breast cancer: long-term follow-up of the Copenhagen breast cancer trial. Acta Oncol. 2018 Jan;57(1):26-30. Epub 2017 Nov 22. link to original article PubMed
Metastatic disease, endocrine therapy
Abemaciclib & Anastrozole
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Goetz et al. 2017 (MONARCH 3) | Phase III | Anastrozole | Superior PFS |
Chemotherapy
- Abemaciclib (Verzenio) 150 mg PO BID
- Anastrozole (Arimidex) 1 mg PO once per day
28-day cycles
References
- Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. link to original article contains verified protocol PubMed
Abemaciclib & Fulvestrant
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sledge et al. 2017 (MONARCH 2) | Phase III | Fulvestrant | Superior PFS |
Chemotherapy
- Abemaciclib (Verzenio) 150 mg PO BID
- Fulvestrant (Faslodex) as follows:
- Cycle 1: 500 mg IM once per day on days 1 & 15
- Cycle 2 onwards: 500 mg IM once on day 1
28-day cycles
References
- Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. Epub 2017 Jun 3. link to original article contains verified protocol PubMed
Abemaciclib & Letrozole
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Goetz et al. 2017 (MONARCH 3) | Phase III | Letrozole | Superior PFS |
Chemotherapy
- Abemaciclib (Verzenio) 150 mg PO BID
- Letrozole (Femara) 2.5 mg PO once per day
28-day cycles
References
- Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. link to original article contains verified protocol PubMed
Anastrozole monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Howell et al. 2002 | Phase III | Fulvestrant | Seems to have non-inferior TTP |
Bergh et al. 2012 (FACT) | Phase III | Anastrozole & Fulvestrant | Seems not superior |
Mehta et al. 2012 (SWOG S0226) | Phase III | Anastrozole & Fulvestrant | Seems to have inferior OS |
Robertson et al. 2016 (FALCON) | Phase III | Fulvestrant | Seems to have inferior PFS |
Goetz et al. 2017 (MONARCH 3) | Phase III | Abemaciclib & Anastrozole | Inferior PFS |
Tripathy et al. 2017 (MONALEESA-7) | Phase III | Anastrozole & Ribociclib | Inferior PFS |
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
Supportive medications
- For premenopausal patients:
- MONALEESA-7: Goserelin (Zoladex) 3.8 mg SC once every 28 days
References
- Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002 Aug 15;20(16):3396-403. link to original article PubMed
- Bergh J, Jönsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D, Lindemann JP, Wiklund F, Henriksson R. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012 Jun 1;30(16):1919-25. Epub 2012 Feb 27. link to original article contains verified protocol PubMed
- Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. link to original article contains verified protocol link to PMC article PubMed
- Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. Epub 2016 Nov 28. link to original article contains protocol PubMed
- Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. link to original article contains verified protocol PubMed
- Abstract: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 link to abstract contains protocol
Anastrozole & Fulvestrant
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bergh et al. 2012 (FACT) | Phase III | Anastrozole | Seems not superior |
Mehta et al. 2012 (SWOG S0226) | Phase III | Anastrozole | Seems to have superior OS |
Endocrine therapy
- Anastrozole (Arimidex) 1 mg PO once per day
- Fulvestrant (Faslodex) 500 mg IM once on day 1, then 250 mg IM once per day on days 14 & 28, then 250 mg IM once every four weeks
- Patients in SWOG S0226 who progressed while on therapy were allowed to receive a higher dose, 500 mg IM once every four weeks
28-day cycles
References
- Bergh J, Jönsson PE, Lidbrink EK, Trudeau M, Eiermann W, Brattström D, Lindemann JP, Wiklund F, Henriksson R. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol. 2012 Jun 1;30(16):1919-25. Epub 2012 Feb 27. link to original article contains verified protocol PubMed
- Mehta RS, Barlow WE, Albain KS, Vandenberg TA, Dakhil SR, Tirumali NR, Lew DL, Hayes DF, Gralow JR, Livingston RB, Hortobagyi GN. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012 Aug 2;367(5):435-44. link to original article contains verified protocol link to PMC article PubMed
Anastrozole & Ribociclib
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tripathy et al. 2017 (MONALEESA-7) | Phase III | Anastrozole | Superior PFS |
Therapy
- Anastrozole (Arimidex) 1 mg PO once per day
- Ribociclib (Kisqali) 600 mg PO once per day on days 1 to 21
Supportive medications
- Goserelin (Zoladex) 3.8 mg SC once every 28 days
28-day cycles
References
- Abstract: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 link to abstract contains protocol
Exemestane monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chia et al. 2008 (EFECT) | Phase III | Fulvestrant | Seems not superior |
Baselga et al. 2011 (BOLERO-2) | Phase III | Everolimus & Exemestane | Inferior PFS |
Endocrine therapy
- Exemestane (Aromasin) 25 mg PO once per day
References
- Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, Fein L, Romieu G, Buzdar A, Robertson JF, Brufsky A, Possinger K, Rennie P, Sapunar F, Lowe E, Piccart M. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008 Apr 1;26(10):1664-70. Epub 2008 Mar 3. link to original article PubMed
- Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7. link to original article contains verified protocol PubMed
- Update: Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. link to PMC article PubMed
See references for Exemestane (Aromasin)
Exemestane & Everolimus
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Baselga et al. 2011 (BOLERO-2) | Phase III | Exemestane | Superior PFS |
Therapy
- Everolimus (Afinitor) 10 mg PO once per day
- Exemestane (Aromasin) 25 mg PO once per day
Given until progression of disease or unacceptable toxicity
References
- Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7. link to original article contains verified protocol PubMed
- Update: Yardley DA, Noguchi S, Pritchard KI, Burris HA 3rd, Baselga J, Gnant M, Hortobagyi GN, Campone M, Pistilli B, Piccart M, Melichar B, Petrakova K, Arena FP, Erdkamp F, Harb WA, Feng W, Cahana A, Taran T, Lebwohl D, Rugo HS. Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013 Oct;30(10):870-84. Erratum in: Adv Ther. 2014 Sep;31(9):1008-9. link to PMC article PubMed
Fulvestrant monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Howell et al. 2002 | Phase III | Anastrozole | Seems to have non-inferior TTP |
Howell et al. 2004 | Phase III | Tamoxifen | Might have inferior TTP |
Chia et al. 2008 (EFECT) | Phase III | Exemestane | Seems not superior |
Di Leo et al. 2010 (CONFIRM) | Phase III | Fulvestrant 250 mg | Superior PFS |
Turner et al. 2015 (PALOMA-3) | Phase III (C) | Fulvestrant & Palbociclib | Inferior PFS |
Robertson et al. 2016 (FALCON) | Phase III | Anastrozole | Seems to have superior PFS |
Baselga et al. 2017 (BELLE-2) | Phase III (C) | Buparlisib & Fulvestrant | Inferior PFS |
Sledge et al. 2017 (MONARCH 2) | Phase III (C) | Abemaciclib & Fulvestrant | Inferior PFS |
Di Leo et al. 2017 (BELLE-3) | Phase III (C) | Buparlisib & Fulvestrant | Inferior PFS |
Note: while this regimen was inferior in BELLE-2 and BELLE-3, the authors note that "no further studies [of this combination] are being pursued because of the toxicity associated with [the experimental arm]."
Endocrine therapy
- Fulvestrant (Faslodex) as follows:
- Cycle 1: 500 mg IM once per day on days 1 & 15
- Cycle 2 onwards: 500 mg IM once on day 1
28-day cycles
References
- Howell A, Robertson JF, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002 Aug 15;20(16):3396-403. link to original article PubMed
- Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004 May 1;22(9):1605-13. link to original article PubMed
- Perey L, Paridaens R, Hawle H, Zaman K, Nolé F, Wildiers H, Fiche M, Dietrich D, Clément P, Köberle D, Goldhirsch A, Thürlimann B. Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol. 2007 Jan;18(1):64-9. Epub 2006 Oct 9. link to original article PubMed
- Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M, Fein L, Romieu G, Buzdar A, Robertson JF, Brufsky A, Possinger K, Rennie P, Sapunar F, Lowe E, Piccart M. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol. 2008 Apr 1;26(10):1664-70. Epub 2008 Mar 3. link to original article PubMed
- Di Leo A, Jerusalem G, Petruzelka L, Torres R, Bondarenko IN, Khasanov R, Verhoeven D, Pedrini JL, Smirnova I, Lichinitser MR, Pendergrass K, Garnett S, Lindemann JP, Sapunar F, Martin M. Results of the CONFIRM phase III trial comparing fulvestrant 250 mg with fulvestrant 500 mg in postmenopausal women with estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2010 Oct 20;28(30):4594-600. Epub 2010 Sep 20. Erratum in: J Clin Oncol. 2011 Jun 1;29(16):2293. link to original articlePubMed
- Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. Epub 2015 Jun 1. link to original article contains verified protocol PubMed
- Update: Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-39. Epub 2016 Mar 3. link to original articlePubMed
- Robertson JF, Bondarenko IM, Trishkina E, Dvorkin M, Panasci L, Manikhas A, Shparyk Y, Cardona-Huerta S, Cheung KL, Philco-Salas MJ, Ruiz-Borrego M, Shao Z, Noguchi S, Rowbottom J, Stuart M, Grinsted LM, Fazal M, Ellis MJ. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): an international, randomised, double-blind, phase 3 trial. Lancet. 2016 Dec 17;388(10063):2997-3005. Epub 2016 Nov 28. link to original article contains protocol PubMed
- Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiełło-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):904-916. Epub 2017 May 30. link to original articlelink to PMC article contains protocol PubMed
- Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke EM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Llombart-Cussac A. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017 Sep 1;35(25):2875-2884. Epub 2017 Jun 3. link to original article contains verified protocol PubMed
- Di Leo A, Johnston S, Lee KS, Ciruelos E, Lønning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, Csőszi T, Bordonaro R, Decker T, Tjan-Heijnen VCG, Blau S, Schirone A, Weber D, El-Hashimy M, Dharan B, Sellami D, Bachelot T. Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):87-100. Epub 2017 Dec 7. link to original article contains protocol PubMed
Fulvestrant & Palbociclib
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Turner et al. 2015 (PALOMA-3) | Phase III | Fulvestrant | Superior PFS |
Therapy
- Fulvestrant (Faslodex) 500 mg IM once every 2 weeks for 3 doses, then once every 4 weeks
- Palbociclib (Ibrance) 125 mg PO once per day on days 1 to 21
28-day cycles
References
- Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M; PALOMA3 Study Group. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jul 16;373(3):209-19. Epub 2015 Jun 1. link to original article contains verified protocol PubMed
- Update: Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, Iwata H, Harbeck N, Zhang K, Theall KP, Jiang Y, Bartlett CH, Koehler M, Slamon D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016 Apr;17(4):425-39. Epub 2016 Mar 3. link to original article PubMed
Letrozole monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Wolff et al. 2012 | Phase III (C) | Letrozole & Temsirolimus | Seems not superior |
Finn et al. 2015 (PALOMA-1/TRIO-18) | Randomized Phase II (C) | Letrozole & Palbociclib | Inferior PFS |
Dickler et al. 2016 (CALGB 40503) | Phase III (C) | Letrozole & Bevacizumab | Seems to have inferior PFS |
Hortobagyi et al. 2016 (MONALEESA-2) | Phase III (C) | Letrozole & Ribociclib | Inferior PFS |
Finn et al. 2016 (PALOMA-2) | Randomized Phase II (C) | Letrozole & Palbociclib | Inferior PFS |
Goetz et al. 2017 (MONARCH 3) | Phase III (C) | Abemaciclib & Letrozole | Inferior PFS |
Tripathy et al. 2017 (MONALEESA-7) | Phase III (C) | Letrozole & Ribociclib | Inferior PFS |
Endocrine therapy
- Letrozole (Femara) 2.5 mg PO once per day
Supportive medications
- For premenopausal patients:
- MONALEESA-7: Goserelin (Zoladex) 3.8 mg SC once every 28 days
References
See references for Letrozole (Femara)
- Wolff AC, Lazar AA, Bondarenko I, Garin AM, Brincat S, Chow L, Sun Y, Neskovic-Konstantinovic Z, Guimaraes RC, Fumoleau P, Chan A, Hachemi S, Strahs A, Cincotta M, Berkenblit A, Krygowski M, Kang LL, Moore L, Hayes DF. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013 Jan 10;31(2):195-202. Epub 2012 Dec 10. link to original article link to PMC article contains protocol PubMed
- Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. link to original article contains verified protocol PubMed
- Dickler MN, Barry WT, Cirrincione CT, Ellis MJ, Moynahan ME, Innocenti F, Hurria A, Rugo HS, Lake DE, Hahn O, Schneider BP, Tripathy D, Carey LA, Winer EP, Hudis CA. Phase III trial evaluating letrozole as first-line endocrine therapy with or without bevacizumab for the treatment of postmenopausal women with hormone receptor-positive advanced-stage breast cancer: CALGB 40503 (Alliance). J Clin Oncol. 2016 Aug 1;34(22):2602-9. Epub 2016 May 2. link to original article contains protocol link to PMC article PubMed
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. Epub 2016 Oct 7.link to original article contains verified protocol PubMed
- Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. link to original article contains verified protocol PubMed
- Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, Park IH, Trédan O, Chen SC, Manso L, Freedman OC, Garnica Jaliffe G, Forrester T, Frenzel M, Barriga S, Smith IC, Bourayou N, Di Leo A. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017 Nov 10;35(32):3638-3646. Epub 2017 Oct 2. link to original article contains verified protocol PubMed
- Abstract: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 link to abstract contains protocol
Letrozole & Palbociclib
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Finn et al. 2015 (PALOMA-1/TRIO-18) | Randomized Phase II | Letrozole | Superior PFS |
Finn et al. 2016 (PALOMA-2) | Phase III | Letrozole | Superior PFS |
Therapy
- Letrozole (Femara) 2.5 mg PO once per day
- Palbociclib (Ibrance) 125 mg PO once per day on days 1 to 21
28-day cycles
References
- Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. link to original article contains verified protocol PubMed
- Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, Gauthier E, Lu DR, Randolph S, Diéras V, Slamon DJ. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016 Nov 17;375(20):1925-1936. link to original article contains verified protocol PubMed
Letrozole & Ribociclib
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hortobagyi et al. 2016 (MONALEESA-2) | Phase III | Letrozole | Superior PFS |
Tripathy et al. 2017 (MONALEESA-7) | Phase III | Letrozole | Superior PFS |
Therapy
- Letrozole (Femara) 2.5 mg PO once per day
- Ribociclib (Kisqali) 600 mg PO once per day on days 1 to 21
Supportive medications
- For premenopausal patients:
- MONALEESA-7: Goserelin (Zoladex) 3.8 mg SC once every 28 days
28-day cycles
References
- Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. Epub 2016 Oct 7. link to original article contains verified protocol PubMed
- Abstract: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 link to abstract contains protocol
Ribociclib & Tamoxifen
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tripathy et al. 2017 (MONALEESA-7) | Phase III | Tamoxifen | Superior PFS |
Therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
- Ribociclib (Kisqali) 600 mg PO once per day on days 1 to 21
Supportive medications
- Goserelin (Zoladex) 3.8 mg SC once on day 1
28-day cycles
References
- Abstract: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 link to abstract contains protocol
Tamoxifen monotherapy
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Regimen #1, standard dosing (20 mg per day)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hayes et al. 1995 | Phase III | Toremifene 60 mg per day | Seems not superior |
Toremifene 200 mg per day | Seems not superior | ||
Howell et al. 2004 | Phase III | Fulvestrant | Might have superior TTP |
Bachelot et al. 2012 | Randomized Phase II | Tamoxifen & Everolimus | Inferior OS |
Tripathy et al. 2017 (MONALEESA-7) | Phase III | Ribociclib & Tamoxifen | Inferior PFS |
Endocrine therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
Supportive medications
- For premenopausal patients:
- MONALEESA-7: Goserelin (Zoladex) 3.8 mg SC once every 28 days
Regimen #2, high-dose (40 mg per day)
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gershanovich et al. 1997 | Phase III | Toremifene 60 mg per day | Seems not superior |
Toremifene 240 mg per day | Seems not superior | ||
Pyrhönen et al. 1997 | Phase III | Toremifene 60 mg per day | Seems to have superior TTP |
Endocrine therapy
- Tamoxifen (Nolvadex) 40 mg PO once per day
References
- Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA, Jones SE, Vogel CL, Berris RF, Shemano I et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2556-66. link to original article PubMed
- Gershanovich M, Garin A, Baltina D, Kurvet A, Kangas L, Ellmén J. A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer. Eastern European Study Group. Breast Cancer Res Treat. 1997 Sep;45(3):251-62. link to original article PubMed
- Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, Bauer J, Westman G, Lundgren S, Blanco G, Mella O, Nilsson I, Hietanen T, Hindy I, Vuorinen J, Hajba A. Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study. Br J Cancer. 1997;76(2):270-7. link to PMC article PubMed
- Howell A, Robertson JF, Abram P, Lichinitser MR, Elledge R, Bajetta E, Watanabe T, Morris C, Webster A, Dimery I, Osborne CK. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004 May 1;22(9):1605-13. link to original article PubMed
- Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: A GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24. Epub 2012 May 7. link to original article contains verified protocol PubMed
- Abstract: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. 2017 Dec SABCS Abstract 828 link to abstract contains protocol
See references for Tamoxifen (Nolvadex)
Tamoxifen & Everolimus
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bachelot et al. 2012 | Randomized Phase II | Tamoxifen | Superior OS |
Therapy
- Tamoxifen (Nolvadex) 20 mg PO once per day
- Everolimus (Afinitor) 10 mg PO once per day
Given until progression of disease or unacceptable toxicity
References
- Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, Legouffe E, Allouache D, El Kouri C, Pujade-Lauraine E. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: A GINECO study. J Clin Oncol. 2012 Aug 1;30(22):2718-24. Epub 2012 May 7. link to original article contains verified protocol PubMed
Toremifene monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hayes et al. 1995 | Phase III | Tamoxifen | Seems not superior |
Toremifene 200 mg per day | Seems not superior | ||
Gershanovich et al. 1997 | Phase III | Tamoxifen 40 mg per day | Seems not superior |
Toremifene 240 mg per day | Seems not superior | ||
Pyrhönen et al. 1997 | Phase III | Tamoxifen 40 mg per day | Seems to have inferior TTP |
Endocrine therapy
- Toremifene (Fareston) 60 mg PO once per day
Given until progression
References
- Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA, Jones SE, Vogel CL, Berris RF, Shemano I et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995 Oct;13(10):2556-66. link to original article PubMed
- Gershanovich M, Garin A, Baltina D, Kurvet A, Kangas L, Ellmén J. A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer. Eastern European Study Group. Breast Cancer Res Treat. 1997 Sep;45(3):251-62. link to original article PubMed
- Pyrhönen S, Valavaara R, Modig H, Pawlicki M, Pienkowski T, Gundersen S, Bauer J, Westman G, Lundgren S, Blanco G, Mella O, Nilsson I, Hietanen T, Hindy I, Vuorinen J, Hajba A. Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study. Br J Cancer. 1997;76(2):270-7. link to PMC article PubMed
- Toremifene (Fareston) package insert
Metastatic disease, single agent therapy
Abemaciclib monotherapy
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Regimen
Study | Evidence | ORR |
---|---|---|
Dickler et al. 2017 (MONARCH 1) | Phase II | 20% (95% CI 13-27.5) |
Chemotherapy
- Abemaciclib (Verzenio) 200 mg PO BID
Continued until progression
References
- Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, Yardley DA, Frenzel M, Koustenis A, Baselga J. MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 Inhibitor, as a single agent, in patients with refractory HR(+)/HER2(-) metastatic breast cancer. Clin Cancer Res. 2017 Sep 1;23(17):5218-5224. Epub 2017 May 22. link to original article link to PMC article contains protocol PubMed
Capecitabine monotherapy
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Regimen #1, 650 mg/m2 BID, continuous
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Stockler et al. 2011 | Phase III | CMF | Seems to have superior OS |
Intermittent Capecitabine | Seems not superior |
Chemotherapy
- Capecitabine (Xeloda) 650 mg/m2 PO BID
21-day cycles
Regimen #2, 1000 mg/m2 BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bajetta et al. 2005 | Phase II | ||
Robert et al. 2011 (RIBBON-1) | Phase III | Capecitabine & Bevacizumab | Inferior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Capecitabine & Bevacizumab | Inferior PFS |
Stockler et al. 2011 | Phase III | CMF | Seems to have superior OS |
Continuous Capecitabine | Seems not superior |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
21-day cycles
Regimen #3, 1250 mg/m2 BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bajetta et al. 2005 | Phase II | ||
Geyer et al. 2006 | Phase III | Capecitabine & Lapatinib | Inferior TTP |
Thomas et al. 2007 | Phase III | Capecitabine & Ixabepilone | Inferior PFS |
von Minckwitz et al. 2009 (GBG 26/BIG 3-05) | Phase III | Capecitabine & Trastuzumab | Seems to have inferior TTP |
Sparano et al. 2010 | Phase III | Capecitabine & Ixabepilone | Inferior PFS |
Crown et al. 2013 | Phase III | Capecitabine & Sunitinib | Seems not superior |
Harbeck et al. 2016 (PELICAN) | Phase III | Pegylated liposomal doxorubicin | Inconclusive whether non-inferior |
Yamamoto et al. 2016 (JO21095) | Non-randomized portion of RCT | ||
Zhang et al. 2017 (BG01-1323L) | Phase III | Capecitabine & Utidelone | Inferior PFS |
Robson et al. 2017 (OlympiAD) | Phase III | Olaparib | Inferior PFS |
Patients in GBG 26/BIG 3-05 had HER2-positive disease. Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.
Preceding treatment
- JO21095: Docetaxel, with PD
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID on days 1 to 14
21-day cycles
References
- Bajetta E, Procopio G, Celio L, Gattinoni L, Della Torre S, Mariani L, Catena L, Ricotta R, Longarini R, Zilembo N, Buzzoni R. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005 Apr 1;23(10):2155-61. Epub 2005 Feb 14. link to original article contains verified protocol PubMed
- Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. link to original article contains verified protocol PubMed
- Update: Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. link to original article PubMed
- Update: Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. link to original article link to PMC article PubMed
- Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed
- von Minckwitz G, du Bois A, Schmidt M, Maass N, Cufer T, de Jongh FE, Maartense E, Zielinski C, Kaufmann M, Bauer W, Baumann KH, Clemens MR, Duerr R, Uleer C, Andersson M, Stein RC, Nekljudova V, Loibl S. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast cancer: a German Breast Group 26/Breast International Group 03-05 study. J Clin Oncol. 2009 Apr 20;27(12):1999-2006. Epub 2009 Mar 16. link to original article contains verified protocol PubMed
- Update: von Minckwitz G, Schwedler K, Schmidt M, Barinoff J, Mundhenke C, Cufer T, Maartense E, de Jongh FE, Baumann KH, Bischoff J, Harbeck N, Lück HJ, Maass N, Zielinski C, Andersson M, Stein RC, Nekljudova V, Loibl S; GBG 26/BIG 03-05 study group and participating investigators. Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer. Eur J Cancer. 2011 Oct;47(15):2273-81. Epub 2011 Jul 7. link to original article contains verified protocol PubMed
- Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63.link to original article contains verified protocol link to PMC article PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. Epub 2011 Oct 24. link to original article contains verified protocol PubMed
- Crown JP, Diéras V, Staroslawska E, Yardley DA, Bachelot T, Davidson N, Wildiers H, Fasching PA, Capitain O, Ramos M, Greil R, Cognetti F, Fountzilas G, Blasinska-Morawiec M, Liedtke C, Kreienberg R, Miller WH Jr, Tassell V, Huang X, Paolini J, Kern KA, Romieu G. Phase III trial of sunitinib in combination with capecitabine versus capecitabine monotherapy for the treatment of patients with pretreated metastatic breast cancer. J Clin Oncol. 2013 Aug 10;31(23):2870-8. Epub 2013 Jul 15. link to original article contains verified protocol PubMed
- Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Lück HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE; PELICAN Investigators. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat. 2017 Jan;161(1):63-72. Epub 2016 Oct 31. link to original article link to PMC article contains verified protocol PubMed
- Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. link to original article contains verified protocol PubMed
- Zhang P, Sun T, Zhang Q, Yuan Z, Jiang Z, Wang XJ, Cui S, Teng Y, Hu XC, Yang J, Pan H, Tong Z, Li H, Yao Q, Wang Y, Yin Y, Sun P, Zheng H, Cheng J, Lu J, Zhang B, Geng C, Liu J, Peng R, Yan M, Zhang S, Huang J, Tang L, Qiu R, Xu B; BG01-1323L study group. Utidelone plus capecitabine versus capecitabine alone for heavily pretreated metastatic breast cancer refractory to anthracyclines and taxanes: a multicentre, open-label, superiority, phase 3, randomised controlled trial. Lancet Oncol. 2017 Mar;18(3):371-383. Epub 2017 Feb 11. link to original article contains protocol PubMed
- Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Docetaxel monotherapy
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D: Docetaxel
T: Taxotere (Docetaxel)
Regimen #1, 40 mg/m2 6 weeks out of 8
Study | Evidence |
---|---|
Burstein et al. 2000 | Phase II |
Chemotherapy
- Docetaxel (Taxotere) 40 mg/m2 IV once per week for weeks 1 to 6, then off for weeks 7 & 8
8-week cycles
Regimen #2, 60 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Harvey et al. 2006 | Phase III | Lower-dose q3wk docetaxel | Might have inferior TTP | |
Standard-dose q3wk docetaxel | Might have inferior TTP | |||
Takashima et al. 2015 (SELECT BC) | Phase III | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycles
Regimen #3, 60 mg/m2 q4wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
28-day cycles
Regimen #4, 70 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yamamoto et al. 2016 (JO21095) | Phase III | Capecitabine & Docetaxel | Seems to have inferior OS |
Chemotherapy
- Docetaxel (Taxotere) 70 mg/m2 IV once on day 1
21-day cycles
'At progression, this arm was pre-assigned to transition to capecitabine.
Regimen #5, 75 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Harvey et al. 2006 | Phase III | Low-dose q3wk docetaxel | Might have superior TTP | |
Standard-dose q3wk docetaxel | Might have inferior TTP | |||
Robert et al. 2011 (RIBBON-1) | Phase III | Docetaxel & Bevacizumab | Inferior PFS | |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Docetaxel & Bevacizumab | Inferior PFS | |
Takashima et al. 2015 (SELECT BC) | Phase III | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
Regimen #6, 75 mg/m2 q4wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
28-day cycles
Regimen #7, 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chan et al. 1999 (303 Study Group) | Phase III | Doxorubicin | Superior ORR |
O'Shaughnessy et al. 2002 | Phase III | Capecitabine & Docetaxel | Seems to have inferior OS |
Marty et al. 2005 (M77001) | Phase III | Docetaxel & Trastuzumab | Seems to have inferior OS |
Harvey et al. 2006 | Phase III | Low-dose q3wk docetaxel | Might have superior TTP |
Lower-dose q3wk docetaxel | Might have superior TTP | ||
Gradishar et al. 2009 | Phase III | Higher-dose weekly nanoparticle albumin-bound paclitaxel | Inferior PFS |
Lower-dose weekly nanoparticle albumin-bound paclitaxel | Seems not superior | ||
q3wk nanoparticle albumin-bound paclitaxel | Seems not superior | ||
Robert et al. 2011 (RIBBON-1) | Phase III | Docetaxel & Bevacizumab | Inferior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Docetaxel & Bevacizumab | Inferior PFS |
Nielsen et al. 2011 (DBCCG) | Phase III | Docetaxel & Gemcitabine | Might have inferior TTP |
Bergh et al. 2012 | Phase III | Docetaxel & Sunitinib | Seems not superior |
Note: the 303 Study Group stopped treatment after 7 cycles.
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycles
References
- Review: Burris HA 3rd. Single-agent docetaxel (Taxotere) in randomized phase III trials. Semin Oncol. 1999 Jun;26(3 Suppl 9):1-6. PubMed
- Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. link to original article PubMed
- Alexandre J, Bleuzen P, Bonneterre J, Sutherland W, Misset JL, Guastalla J, Viens P, Faivre S, Chahine A, Spielman M, Bensmaïne A, Marty M, Mahjoubi M, Cvitkovic E. Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients. J Clin Oncol. 2000 Feb;18(3):562-73. link to original article PubMed
- Burstein HJ, Manola J, Younger J, Parker LM, Bunnell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP. Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol. 2000 Mar;18(6):1212-9. link to original article PubMed content property of HemOnc.org
- O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. link to original article contains verified protocol PubMed
- Marty M, Cognetti F, Maraninchi D, Snyder R, Mauriac L, Tubiana-Hulin M, Chan S, Grimes D, Antón A, Lluch A, Kennedy J, O'Byrne K, Conte P, Green M, Ward C, Mayne K, Extra JM. Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol. 2005 Jul 1;23(19):4265-74. Epub 2005 May 23. link to original article contains verified protocol PubMed
- Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006 Nov 1;24(31):4963-70. Epub 2006 Oct 10. link to original article PubMed
- Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. Epub 2009 May 26. Erratum in: J Clin Oncol. 2011 Jul 1;29(19):2739. link to original article contains verified protocol PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Nielsen DL, Bjerre KD, Jakobsen EH, Cold S, Stenbygaard L, Sørensen PG, Kamby C, Møller S, Jørgensen CL, Andersson M. Gemcitabine plus docetaxel versus docetaxel in patients with predominantly human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: a randomized, phase III study by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 2011 Dec 20;29(36):4748-54. Epub 2011 Nov 14. link to original article contains protocol PubMed
- Bergh J, Bondarenko IM, Lichinitser MR, Liljegren A, Greil R, Voytko NL, Makhson AN, Cortes J, Lortholary A, Bischoff J, Chan A, Delaloge S, Huang X, Kern KA, Giorgetti C. First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study. J Clin Oncol. 2012 Mar 20;30(9):921-9. Epub 2012 Feb 13. link to original article contains verified protocol PubMed
- Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
- Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. link to original article contains verified protocol PubMed
Doxorubicin monotherapy
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Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Brien et al. 2004 (CAELYX Breast Cancer Study Group) | Phase III | Pegylated liposomal doxorubicin | Seems to have non-inferior PFS |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
21-day cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Chan et al. 1999 (303 Study Group) | Phase III | Docetaxel | Inferior ORR |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
21-day cycle for up to 7 cycles
Regimen #3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gundersen et al. 1986 | Phase III | VAC | Seems not superior |
Chemotherapy
- Doxorubicin (Adriamycin) 20 mg/m2 IV once per week
Duration not specified
References
- Gundersen S, Kvinnsland S, Klepp O, Kvaløy S, Lund E, Høst H. Weekly adriamycin versus VAC in advanced breast cancer. A randomized trial. Eur J Cancer Clin Oncol. 1986 Dec;22(12):1431-4. link to SD article PubMed
- Chan S, Friedrichs K, Noel D, Pintér T, Van Belle S, Vorobiof D, Duarte R, Gil Gil M, Bodrogi I, Murray E, Yelle L, von Minckwitz G, Korec S, Simmonds P, Buzzi F, González Mancha R, Richardson G, Walpole E, Ronzoni M, Murawsky M, Alakl M, Riva A, Crown J; 303 Study Group. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2341-54. link to original article PubMed
- O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. link to original article PubMed
Doxorubicin liposomal monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Brien et al. 2004 (CAELYX Breast Cancer Study Group) | Phase III | Doxorubicin | Seems to have non-inferior PFS |
Harbeck et al. 2016 (PELICAN) | Phase III | Capecitabine | Inconclusive whether non-inferior |
Chemotherapy
- Pegylated liposomal doxorubicin (Doxil) 50 mg/m2 IV over up to 60 minutes once on day 1
- If infusion reactions occurred, infusion could be given over up to 90 minutes
28-day cycles
References
- O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C; CAELYX Breast Cancer Study Group. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9. link to original article contains verified protocol PubMed
- Harbeck N, Saupe S, Jäger E, Schmidt M, Kreienberg R, Müller L, Otremba BJ, Waldenmaier D, Dorn J, Warm M, Scholz M, Untch M, de Wit M, Barinoff J, Lück HJ, Harter P, Augustin D, Harnett P, Beckmann MW, Al-Batran SE; PELICAN Investigators. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study. Breast Cancer Res Treat. 2017 Jan;161(1):63-72. Epub 2016 Oct 31. link to original article link to PMC article contains verified protocol PubMed
Epirubicin monotherapy
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Regimen #1, 40 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III | Epirubicin 60 mg/m2 | Seems not superior |
Epirubicin 90 mg/m2 | Inferior TTP | ||
Epirubicin 135 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 40 mg/m2 IV once on day 1
21-day cycles
Regimen #2, 60 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III | Epirubicin 40 mg/m2 | Seems not superior |
Epirubicin 90 mg/m2 | Seems not superior | ||
Epirubicin 135 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
21-day cycles
Regimen #3, 90 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III | Epirubicin 40 mg/m2 | Superior TTP |
Epirubicin 60 mg/m2 | Seems not superior | ||
Epirubicin 135 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 90 mg/m2 IV once on day 1
21-day cycles
Regimen #4, 135 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bastholt et al. 1996 | Phase III | Epirubicin 40 mg/m2 | Seems not superior |
Epirubicin 60 mg/m2 | Seems not superior | ||
Epirubicin 90 mg/m2 | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 135 mg/m2 IV once on day 1
21-day cycles
References
- Bastholt L, Dalmark M, Gjedde SB, Pfeiffer P, Pedersen D, Sandberg E, Kjaer M, Mouridsen HT, Rose C, Nielsen OS, Jakobsen P, Bentzen SM. Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 1996 Apr;14(4):1146-55. link to original article contains verified protocol PubMed
Eribulin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Cortes et al. 2011 (EMBRACE) | Phase III | Investigator's choice | Seems to have superior OS |
Robson et al. 2017 (OlympiAD) | Phase III | Olaparib | Inferior PFS |
Patients in OlympiAD had confirmed deleterious or suspected deleterious germline BRCA mutation.
Chemotherapy
- Eribulin (Halaven) 1.4 mg/m2 IV over 2 to 5 minutes once per day on days 1 & 8
21-day cycles
References
- Cortes J, O'Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, Chollet P, Manikas A, Diéras V, Delozier T, Vladimirov V, Cardoso F, Koh H, Bougnoux P, Dutcus CE, Seegobin S, Mir D, Meneses N, Wanders J, Twelves C; EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) investigators. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011 Mar 12;377(9769):914-23. Epub 2011 Mar 2. link to original article contains protocol PubMed
- Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Gemcitabine monotherapy
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Regimen #1, 800 mg/m2 3 weeks out of 4
Study | Evidence |
---|---|
Carmichael et al. 1995 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Regimen #2, 1200 mg/m2 3 weeks out of 4
Study | Evidence |
---|---|
Spielmann et al. 2001 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycles
Regimen #3, 1250 mg/m2 2 weeks out of 3
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III | Gemcitabine & Bevacizumab | Inferior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
References
- Carmichael J, Possinger K, Phillip P, Beykirch M, Kerr H, Walling J, Harris AL. Advanced breast cancer: a phase II trial with gemcitabine. J Clin Oncol. 1995 Nov;13(11):2731-6. link to original article PubMed
- Spielmann M, Llombart-Cussac A, Kalla S, Espié M, Namer M, Ferrero JM, Diéras V, Fumoleau P, Cuvier C, Perrocheau G, Ponzio A, Kayitalire L, Pouillart P. Single-agent gemcitabine is active in previously treated metastatic breast cancer. Oncology. 2001;60(4):303-7. link to original article PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Paclitaxel monotherapy
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Regimen #1, 80 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Guan et al. 2013 | Phase III | TL (Taxol) | Seems to have inferior OS |
Patients had HER2+ disease.
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen #2, 80 mg/m2 weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Perez et al. 2001 | Phase II | ||
Seidman et al. 2008 (CALGB 9840) | Phase III | Paclitaxel q3wk | Superior OS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per week
28-day cycles
Regimen #3, 90 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Miller et al. 2007 | Phase III | Paclitaxel & Bevacizumab | Inferior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Paclitaxel & Bevacizumab | Inferior PFS |
Miles et al. 2016 (MERiDiAN) | Phase III | Paclitaxel & Bevacizumab | Inferior PFS |
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen #4, 175 mg/m2 q4wk
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1
28-day cycles
Regimen #5, with range, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III | S-1 | Seems to have non-inferior OS | Inferior EQ-5D score |
Chemotherapy
- Paclitaxel (Taxol) 80 to 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001 Nov 15;19(22):4216-23. link to original article PubMed
- Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. link to original article PubMed
- CALGB 9840: Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. link to original article PubMed
- RIBBON-2: Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Guan Z, Xu B, DeSilvio ML, Shen Z, Arpornwirat W, Tong Z, Lorvidhaya V, Jiang Z, Yang J, Makhson A, Leung WL, Russo MW, Newstat B, Wang L, Chen G, Oliva C, Gomez H. Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2-overexpressing metastatic breast cancer. J Clin Oncol. 2013 Jun 1;31(16):1947-53. Epub 2013 Mar 18. link to original article contains verified protocol PubMed
- SELECT BC: Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
- MERiDiAN: Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. Epub 2016 Nov 4. link to original article contains protocol PubMed
- BELLE-4: Martín M, Chan A, Dirix L, O'Shaughnessy J, Hegg R, Manikhas A, Shtivelband M, Krivorotko P, Batista López N, Campone M, Ruiz Borrego M, Khan QJ, Beck JT, Ramos Vázquez M, Urban P, Goteti S, Di Tomaso E, Massacesi C, Delaloge S. A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4). Ann Oncol. 2017 Feb 1;28(2):313-320. link to original article PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
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Example orders
Regimen #1, 100 mg/m2, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2009 | Randomized Phase II | Docetaxel | Seems not superior |
Weekly nab-paclitaxel (150 mg/m2) | Not reported | ||
q3wk nab-paclitaxel | Not reported |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen #2, 150 mg/m2 weekly, 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2009 | Randomized Phase II | Docetaxel | Superior PFS |
Weekly nab-paclitaxel (100 mg/m2) | Not reported | ||
q3wk nab-paclitaxel | Not reported |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 150 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen #3, 260 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2005 | Phase III | Paclitaxel | Superior TTP |
Robert et al. 2011 (RIBBON-1) | Phase III | nab-Paclitaxel & Bevacizumab | Inferior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | nab-Paclitaxel & Bevacizumab | Inferior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV over 30 minutes once on day 1
Supportive medications
- Gradishar et al. 2005: No corticosteroid or antihistamine premedication
21-day cycles
Regimen #4, 300 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Gradishar et al. 2009 | Randomized Phase II | Docetaxel | Seems not superior |
Weekly nab-paclitaxel (100 mg/m2) | Not reported | ||
Weekly nab-paclitaxel (150 mg/m2) | Not reported |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 300 mg/m2 IV over 30 minutes once on day 1
21-day cycles
References
- Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, Hawkins M, O'Shaughnessy J. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005 Nov 1;23(31):7794-803. Epub 2005 Sep 19. link to original article contains verified protocol PubMed
- Gradishar WJ, Krasnojon D, Cheporov S, Makhson AN, Manikhas GM, Clawson A, Bhar P. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009 Aug 1;27(22):3611-9. Epub 2009 May 26. Erratum in: J Clin Oncol. 2011 Jul 1;29(19):2739. link to original article contains verified protocol PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Pemetrexed monotherapy
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Regimen #1, 500 mg/m2
Study | Evidence |
---|---|
Gomez et al. 2006 | Phase II |
Patients in the study were "chemotherapy-naïve, with advanced (T4 and N0-N2, M0, M1) breast cancer."
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
Supportive medications
- Dexamethasone (Decadron) 4 mg PO BID the day before, day of, and day after chemotherapy
- Folic acid 350 to 1000 mcg PO once per day, to start 5 to 7 days prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, the first dose given before the study's pretreatment biopsy, to continue throughout therapy with pemetrexed
21-day cycle for up to 3 cycles
Regimen #2, 600 mg/m2
Study | Evidence |
---|---|
Robert et al. 2011 | Phase II |
Chemotherapy
- Pemetrexed (Alimta) 600 mg/m2 IV once on day 1
Supportive medications
- Dexamethasone (Decadron) 4 mg PO BID the day before, day of, and day after chemotherapy
- Folic acid 350 to 1000 mcg PO once per day, to start at least 5 days prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed, and until 3 weeks after the last dose of pemetrexed
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 8 to 10 weeks, the first dose given at least 1 week prior to start of pemetrexed therapy, to continue throughout therapy with pemetrexed, and until 3 weeks after the last dose of pemetrexed
14-day cycles
References
- Gomez HL, Santillana SL, Vallejos CS, Velarde R, Sanchez J, Wang X, Bauer NL, Hockett RD, Chen VJ, Niyikiza C, Hanauske AR. A phase II trial of pemetrexed in advanced breast cancer: clinical response and association with molecular target expression. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):832-8. link to original article contains verified protocol PubMed
- Robert NJ, Conkling PR, O'Rourke MA, Kuefler PR, McIntyre KJ, Zhan F, Asmar L, Wang Y, Shonukan OO, O'Shaughnessy JA. Results of a phase II study of pemetrexed as first-line chemotherapy in patients with advanced or metastatic breast cancer. Breast Cancer Res Treat. 2011 Feb;126(1):101-8. Epub 2010 Dec 25. link to original article contains verified protocol PubMed
S-1 monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Takashima et al. 2015 (SELECT BC) | Phase III | Docetaxel Paclitaxel |
Seems to have non-inferior OS | Superior EQ-5D score |
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) as follows:
- BSA less than 1.25 m2: 40 mg PO BID on days 1 to 28
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO BID on days 1 to 28
- BSA 1.5 m2 or more: 60 mg PO BID on days 1 to 28
42-day cycles
References
- SELECT BC: Takashima T, Mukai H, Hara F, Matsubara N, Saito T, Takano T, Park Y, Toyama T, Hozumi Y, Tsurutani J, Imoto S, Watanabe T, Sagara Y, Nishimura R, Shimozuma K, Ohashi Y; SELECT BC Study Group. Taxanes versus S-1 as the first-line chemotherapy for metastatic breast cancer (SELECT BC): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol. 2016 Jan;17(1):90-8. Epub 2015 Nov 27. link to original article contains verified protocol PubMed
- HRQoL analysis: Shiroiwa T, Fukuda T, Shimozuma K, Mouri M, Hagiwara Y, Doihara H, Akabane H, Kashiwaba M, Watanabe T, Ohashi Y, Mukai H. Long-term health status as measured by EQ-5D among patients with metastatic breast cancer: comparison of first-line oral S-1 and taxane therapies in the randomized phase III SELECT BC trial. Qual Life Res. 2017 Feb;26(2):445-453. Epub 2016 Aug 12. link to original article link to PMC article PubMed
Vinorelbine monotherapy
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Regimen #1, 25 mg/m2 weekly
Study | Evidence |
---|---|
Gasparini et al. 1994 | Phase II |
Zelek et al. 2001 | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per week
Regimen #2, 30 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III | Vinorelbine & Bevacizumab | Inferior PFS |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once on day 1
21-day cycles
Regimen #3, 30 mg/m2 2 out of 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robson et al. 2017 (OlympiAD) | Phase III | Olaparib | Inferior PFS |
Patients had confirmed deleterious or suspected deleterious germline BRCA mutation.
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Gasparini G, Caffo O, Barni S, Frontini L, Testolin A, Guglielmi RB, Ambrosini G. Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study. J Clin Oncol. 1994 Oct;12(10):2094-101. link to original article PubMed
- Zelek L, Barthier S, Riofrio M, Fizazi K, Rixe O, Delord JP, Le Cesne A, Spielmann M. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer. 2001 Nov 1;92(9):2267-72. PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. Epub 2017 Jun 4. link to original article contains verified protocol PubMed
Metastatic disease, combination chemotherapy
AC
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AC: Adriamycin (Doxorubicin) & Cyclophosphamide
Regimen #1, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | AC & Bevacizumab | Inferior PFS |
Chemotherapy
- Doxorubicin (Adriamycin) 50 to 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
Regimen #2, 60/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fisher et al. 1990 (NSABP B-15) | Phase III | AC, then CMF | Seems not superior |
CMF | Seems not superior | ||
Slamon et al. 2001 | Phase III | ACH | Seems to have inferior OS |
Nabholtz et al. 2003 | Phase III | AT (Taxotere) | Seems to have inferior TTP |
Note: patients in Slamon et al. 2001 had not previously received adjuvant (postoperative) therapy with an anthracycline.
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycles
References
- Jones SE, Durie BG, Salmon SE. Combination chemotherapy with adriamycin and cyclophosphamide for advanced breast cancer. Cancer. 1975 Jul;36(1):90-7. link to original article PubMed
- Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990 Sep;8(9):1483-96. link to original article PubMed
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003 Mar 15;21(6):968-75. link to original article PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
AC & Bevacizumab
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AC & Bevacizumab: Adriamycin (Doxorubicin), Cyclophosphamide, Bevacizumab
Regimen #1, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | AC | Superior PFS |
Chemotherapy
- Doxorubicin (Adriamycin) 50 to 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
AT (Taxol)
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AT: Adriamycin (Doxorubicin) & Taxol (Paclitaxel)
Regimen
Study | Evidence |
---|---|
Gianni et al. 1995 | Non-randomized |
Chemotherapy
- Doxorubicin (Adriamycin) 60 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 125 to 200 mg/m2 IV once on day 1
21-day cycles
References
- Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, Spreafico C, Laffranchi A, Caraceni A, Martini C et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995 Nov;13(11):2688-99. link to original article PubMed
AT (Taxotere)
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AT: Adriamycin (Doxorubicin), Taxotere (Docetaxel)
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nabholtz et al. 2003 | Phase III | AC | Seems to have superior TTP |
Chemotherapy
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
References
- Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, Pienkowski T, Zaluski J, Pinter T, Krzakowski M, Vorobiof D, Leonard R, Kennedy I, Azli N, Murawsky M, Riva A, Pouillart P; TAX 306 Study Group. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003 Mar 15;21(6):968-75. link to original article PubMed
Capecitabine & Bevacizumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | Capecitabine | Superior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Capecitabine | Superior PFS |
Lang et al. 2013 (TURANDOT) | Phase III | Paclitaxel & Bevacizumab | Non-inferior OS (*) |
Welt et al. 2016 (CARIN) | Phase III | Capecitabine, Vinorelbine, Bevacizumab | Might have inferior PFS |
Note: efficacy for TURANDOT is based on the 2016 update.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 14
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. Epub 2013 Jan 10. link to original article PubMed
- Update: Zielinski C, Láng I, Inbar M, Kahán Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. Epub 2016 Aug 5. link to original article contains protocol PubMed
- Welt A, Marschner N, Lerchenmueller C, Decker T, Steffens CC, Koehler A, Depenbusch R, Busies S, Hegewisch-Becker S. Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial. Breast Cancer Res Treat. 2016 Feb;156(1):97-107. link to PMC article PubMed
Capecitabine & Docetaxel
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TX: Taxotere (Docetaxel) and Xeloda (Capecitabine)
XT: Xeloda (Capecitabine) and Taxotere (Docetaxel)
Regimen #1, 825/60
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Yamamoto et al. 2016 (JO21095) | Phase III | Docetaxel | Seems to have superior PFS |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO BID days 1 to 14
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycles
Regimen #2, 1250/75
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
O'Shaughnessy et al. 2002 | Phase III | Docetaxel | Seems to have superior OS |
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO BID days 1 to 14
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycles
References
- O'Shaughnessy J, Miles D, Vukelja S, Moiseyenko V, Ayoub JP, Cervantes G, Fumoleau P, Jones S, Lui WY, Mauriac L, Twelves C, Van Hazel G, Verma S, Leonard R. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol. 2002 Jun 15;20(12):2812-23. link to original article contains verified protocol PubMed
- Yamamoto D, Sato N, Rai Y, Yamamoto Y, Saito M, Iwata H, Masuda N, Oura S, Watanabe J, Hattori S, Matsuura Y, Kuroi K. Efficacy and safety of low-dose capecitabine plus docetaxel versus single-agent docetaxel in patients with anthracycline-pretreated HER2-negative metastatic breast cancer: results from the randomized phase III JO21095 trial. Breast Cancer Res Treat. 2017 Feb;161(3):473-482. Epub 2016 Dec 22. link to original article contains verified protocol PubMed
Capecitabine & Ixabepilone
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Thomas et al. 2007 | Phase III | Capecitabine | Superior PFS |
Sparano et al. 2010 | Phase III | Capecitabine | Superior PFS |
Chemotherapy
- Capecitabine (Xeloda) 2000 mg/m2 PO once per day on days 1 to 14
- Ixabepilone (Ixempra) 40 mg/m2 IV once on day 1
21-day cycles
References
- Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, Jassem J, Pivot XB, Klimovsky JV, de Mendoza FH, Xu B, Campone M, Lerzo GL, Peck RA, Mukhopadhyay P, Vahdat LT, Roché HH. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007 Nov 20;25(33):5210-7. link to original article contains verified protocol PubMed
- Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, Da Costa SC, Ro J, Rubio G, Rondinon M, Perez Manga G, Peck R, Poulart V, Conte P. Randomized phase III trial of ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010 Jul 10;28(20):3256-63. link to original article contains protocol link to PMC article PubMed
Capecitabine & Paclitaxel
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TX: Taxol (Paclitaxel), Xeloda (Capecitabine)
Regimen
Study | Evidence |
---|---|
Blum et al. 2006 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 (rounded to nearest 500 mg) PO BID on days 1 to 14
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Blum JL, Dees EC, Chacko A, Doane L, Ethirajan S, Hopkins J, McMahon R, Merten S, Negron A, Neubauer M, Ilegbodu D, Boehm KA, Asmar L, O'Shaughnessy JA. Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2006 Sep 20;24(27):4384-90. Epub 2006 Aug 22. link to original article contains verified protocol PubMed
Capecitabine & Paclitaxel, nanoparticle albumin-bound
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Regimen
Study | Evidence |
---|---|
Schwartzberg et al. 2011 | Phase II |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 (rounded to nearest 500 mg) PO BID on days 1 to 15
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 125 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Schwartzberg LS, Arena FP, Mintzer DM, Epperson AL, Walker MS. Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer. Clin Breast Cancer. 2012 Apr;12(2):87-93. Epub 2011 Dec 6. link to original article contains protocol PubMed
Carboplatin & Gemcitabine
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Regimen
Study | Evidence |
---|---|
Nagourney et al. 2008 | Pilot, <20 pts |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV over 60 minutes once per day on days 1 & 8
- Gemcitabine (Gemzar) 800 mg/m2 IV over 60 minutes once per day on days 1 & 8
21-day cycles, given until complete remission, progression of disease, or unacceptable toxicity
References
- Nagourney RA, Flam M, Link J, Hager S, Blitzer J, Lyons W, Sommers BL, Evans S. Carboplatin plus gemcitabine repeating doublet therapy in recurrent breast cancer. Clin Breast Cancer. 2008 Oct;8(5):432-5. link to original article contains protocol PubMed
Cisplatin & Vinorelbine
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Regimen
Study | Evidence |
---|---|
Ray-Coquard et al. 1998 | Phase II |
Vassilomanolakis et al. 2000 | Phase II |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV over 5 to 10 minutes once per day on days 1 & 8
Supportive medications
- Normal saline 200 mL bolus after Vinorelbine (Navelbine) to prevent phlebitis
- Normal saline 2000 mL with KCl (unspecified amount of KCl) IV over 4 hours (infusion rate: 500 mL/H) once prior to Cisplatin (Platinol)
- Furosemide (Lasix) 40 mg IV once 20 minutes prior to Cisplatin (Platinol)
- Normal saline 1000 mL and D5W 1000 mL IV over 4 hours (overall infusion rate: 500 mL/H; paper did not say whether fluids were given sequentially or concurrently) once after Cisplatin (Platinol)
- 5-HT3 antagonists used
21-day cycle for up to 6 cycles or progression of disease
References
- Ray-Coquard I, Biron P, Bachelot T, Guastalla JP, Catimel G, Merrouche Y, Droz JP, Chauvin F, Blay JY. Vinorelbine and cisplatin (CIVIC regimen) for the treatment of metastatic breast carcinoma after failure of anthracycline- and/or paclitaxel-containing regimens. Cancer. 1998 Jan 1;82(1):134-40. PubMed
- Vassilomanolakis M, Koumakis G, Barbounis V, Demiri M, Pateras H, Efremidis AP. Vinorelbine and cisplatin in metastatic breast cancer patients previously treated with anthracyclines. Ann Oncol. 2000 Sep;11(9):1155-60. link to original article contains verified protocol Pubmed
CMF
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CMF: Cyclophosphamide, Methotrexate, Fluorouracil
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bull et al. 1978 | Phase III | CAF | Might have inferior ORR |
Fisher et al. 1990 (NSABP B-15) | Phase III | AC | Seems not superior |
AC, then CMF | Seems not superior | ||
Stadtmauer et al. 2000 (Philadelphia Bone Marrow Transplant Group) | Phase III | CMF x 4-6, then HDT | Seems not superior |
Ackland et al. 2001 (HEPI 013) | Phase III | CEF | Inferior TTP |
Stockler et al. 2011 | Phase III | Continuous Capecitabine Intermittent Capecitabine |
Seems to have inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 40 mg/m2 IV once per day on days 1 & 8
- Fluorouracil (5-FU) 600 mg/m2 IV oncer per day on days 1 & 8
28-day cycles
References
- Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. link to original article PubMed
- Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, Bowman D, Wolmark N, Wickerham DL, Kardinal CG et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990 Sep;8(9):1483-96. link to original article PubMed
- Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia Bone Marrow Transplant Group. N Engl J Med. 2000 Apr 13;342(15):1069-76. link to original article PubMed
- Ackland SP, Anton A, Breitbach GP, Colajori E, Tursi JM, Delfino C, Efremidis A, Ezzat A, Fittipaldo A, Kolaric K, Lopez M, Viaro D; HEPI 013 study group. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001 Feb 15;19(4):943-53. link to original article PubMed
- Stockler MR, Harvey VJ, Francis PA, Byrne MJ, Ackland SP, Fitzharris B, Van Hazel G, Wilcken NR, Grimison PS, Nowak AK, Gainford MC, Fong A, Paksec L, Sourjina T, Zannino D, Gebski V, Simes RJ, Forbes JF, Coates AS. Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer. J Clin Oncol. 2011 Dec 1;29(34):4498-504. Epub 2011 Oct 24. link to original article PubMed
Docetaxel & Bevacizumab
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Regimen #1, docetaxel 75 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | Docetaxel | Superior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Docetaxel | Superior PFS |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
Regimen #2, docetaxel 100 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | Docetaxel | Superior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Docetaxel | Superior PFS |
Chemotherapy
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
EC
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EC: Epirubicin & Cyclophosphamide
Regimen #1, 75/600
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Slamon et al. 2001 | Phase III | ECH | Seems to have inferior OS |
Langley et al. 2005 (UKNCRI AB01) | Phase III | EP | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
Regimen #2, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | EC & Bevacizumab | Inferior PFS |
Chemotherapy
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
References
- Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001 Mar 15;344(11):783-92. link to original article PubMed
- Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscinska B, Howell A, Parmar M. Phase III trial of epirubicin plus paclitaxel compared with epirubicin plus cyclophosphamide as first-line chemotherapy for metastatic breast cancer: United Kingdom National Cancer Research Institute trial AB01. J Clin Oncol. 2005 Nov 20;23(33):8322-30. link to original article PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
EC & Bevacizumab
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EC & Bevacizumab: Epirubicin, Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | EC | Superior PFS |
Chemotherapy
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 to 600 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
EP
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EP: Epirubicin, Paclitaxel
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Langley et al. 2005 (UKNCRI AB01) | Phase III | EC | Seems not superior |
Chemotherapy
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
References
- Langley RE, Carmichael J, Jones AL, Cameron DA, Qian W, Uscinska B, Howell A, Parmar M. Phase III trial of epirubicin plus paclitaxel compared with epirubicin plus cyclophosphamide as first-line chemotherapy for metastatic breast cancer: United Kingdom National Cancer Research Institute trial AB01. J Clin Oncol. 2005 Nov 20;23(33):8322-30. link to original article PubMed
FAC
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FAC: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide
CAF: Cyclophosphamide, Adriamycin (Doxorubicin), Fluorouracil
Regimen #1, 21-day cycles, 5-FU 1 out of 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | FAC & Bevacizumab | Inferior PFS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycle for up to 8 cycles
Regimen #2, 21-day cycles, 5-FU 2 out of 3 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hortobagyi et al. 1979 | Phase III | FAC-BCG | Inferior OS in responders |
Assikis et al. 2003 | Phase III | See link | See link |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8 or days 1 & 4
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
21-day cycles
Subsequent treatment
Regimen #3, 28-day cycles
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Bull et al. 1978 | Phase III | CMF | Might have superior ORR |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Doxorubicin (Adriamycin) 30 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 14
28-day cycles
References
- Bull JM, Tormey DC, Li SH, Carbone PP, Falkson G, Blom J, Perlin E, Simon R. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer. 1978 May;41(5):1649-57. link to original article PubMed
- Hortobagyi GN, Gutterman JU, Blumenschein GR, Tashima CK, Burgess MA, Einhorn L, Buzdar AU, Richman SP, Hersh EM. Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. Cancer. 1979 Nov;44(5):1955-62. link to original article PubMed
- Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. link to original article contains protocol PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
FAC & Bevacizumab
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FAC & Bevacizumab: Fluorouracil, Adriamycin (Doxorubicin), Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | FAC | Superior PFS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
FEC
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FEC: Fluorouracil, Epirubicin, Cyclophosphamide
CEF: Cyclophosphamide, Epirubicin, Fluorouracil
Regimen #1, 500/50/400, 2 out of 4 weeks
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Ackland et al. 2001 (HEPI 013) | Phase III | CMF | Superior TTP |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 8
- Epirubicin (Ellence) 50 mg/m2 IV once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 to 8 cycles
Regimen #2, 500/50/500 ("FEC 50")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufman et al. 1997 (HEPI 010) | Phase III | FEC 100 | Inferior ORR |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycle for 6 to 8 cycles
Regimen #3, 500/100/500 ("FEC 100")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufman et al. 1997 (HEPI 010) | Phase III | FEC 50 | Superior ORR |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycle for 6 to 8 cycles
Regimen #4, 600/60/600 ("CEF21")
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Del Mastro et al. 2001 | Phase III | HD-CEF14 | Seems not superior |
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV once on day 1
- Epirubicin (Ellence) 60 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once once on day 1
21-day cycle for 8 to 12 cycles
Regimen #5, with range
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | FEC & Bevacizumab | Inferior PFS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once once on day 1
21-day cycle for up to 8 cycles
References
- Brufman G, Colajori E, Ghilezan N, Lassus M, Martoni A, Perevodchikova N, Tosello C, Viaro D, Zielinski C. Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer. The Epirubicin High Dose (HEPI 010) Study Group. Ann Oncol. 1997 Feb;8(2):155-62. link to original article contains verified protocol PubMed
- Ackland SP, Anton A, Breitbach GP, Colajori E, Tursi JM, Delfino C, Efremidis A, Ezzat A, Fittipaldo A, Kolaric K, Lopez M, Viaro D; HEPI 013 study group. Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study. J Clin Oncol. 2001 Feb 15;19(4):943-53. link to original article PubMed
- Del Mastro L, Venturini M, Lionetto R, Carnino F, Guarneri D, Gallo L, Contu A, Pronzato P, Vesentini L, Bergaglio M, Comis S, Rosso R. Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group. J Clin Oncol. 2001 Apr 15;19(8):2213-21. link to original article contains verified protocol PubMed
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
FEC & Bevacizumab
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FEC & Bevacizumab: Fluorouracil, Epirubicin, Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | FEC | Superior PFS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once on day 1
- Epirubicin (Ellence) 90 to 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 500 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycle for up to 8 cycles
Subsequent treatment
- Bevacizumab maintenance, if no PD
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
Gemcitabine & Bevacizumab
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III | Gemcitabine | Superior PFS |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
GT (Taxol)
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GT: Gemcitabine & Taxol (Paclitaxel)
PG: Paclitaxel & Gemcitabine
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Albain et al. 2008 | Phase III | Paclitaxel | Seems to have superior OS |
Park et al. 2013 (KCSG-BR07-02) | Phase III | PG x 6 | Seems to have superior OS |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8; on day 1, given last
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1, given first
21-day cycles
References
- Albain KS, Nag SM, Calderillo-Ruiz G, Jordaan JP, Llombart AC, Pluzanska A, Rolski J, Melemed AS, Reyes-Vidal JM, Sekhon JS, Simms L, O'Shaughnessy J. Gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer and prior anthracycline treatment. J Clin Oncol. 2008 Aug 20;26(24):3950-7. link to original article PubMed
- KCSG-BR07-02: Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. link to original article contains verified protocol PubMed
Paclitaxel & Bevacizumab
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Regimen #1, 90 mg/m2 3 weeks out of 4
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Miller et al. 2007 | Phase III | Paclitaxel | Superior PFS |
Lang et al. 2013 (TURANDOT) | Phase III | Capecitabine & Bevacizumab | Non-inferior OS (*) |
Brufsky et al. 2011 (RIBBON-2) | Phase III | Paclitaxel | Superior PFS |
Miles et al. 2016 (MERiDiAN) | Phase III | Paclitaxel | Superior PFS |
Note: efficacy for TURANDOT is based on the 2016 update.
Chemotherapy
- Paclitaxel (Taxol) 90 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
- Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1 & 15
28-day cycles
Regimen #2, 175 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III | Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007 Dec 27;357(26):2666-76. link to original article PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
- Lang I, Brodowicz T, Ryvo L, Kahan Z, Greil R, Beslija S, Stemmer SM, Kaufman B, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Messinger D, Zielinski C; Central European Cooperative Oncology Group. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer: interim efficacy results of the randomised, open-label, non-inferiority, phase 3 TURANDOT trial. Lancet Oncol. 2013 Feb;14(2):125-33. Epub 2013 Jan 10. link to original article PubMed
- Update: Zielinski C, Láng I, Inbar M, Kahán Z, Greil R, Beslija S, Stemmer SM, Zvirbule Z, Steger GG, Melichar B, Pienkowski T, Sirbu D, Petruzelka L, Eniu A, Nisenbaum B, Dank M, Anghel R, Messinger D, Brodowicz T; TURANDOT investigators. Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial. Lancet Oncol. 2016 Sep;17(9):1230-9. Epub 2016 Aug 5. link to original article contains protocol PubMed
- Miles D, Cameron D, Bondarenko I, Manzyuk L, Alcedo JC, Lopez RI, Im SA, Canon JL, Shparyk Y, Yardley DA, Masuda N, Ro J, Denduluri N, Hubeaux S, Quah C, Bais C, O'Shaughnessy J. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation. Eur J Cancer. 2017 Jan;70:146-155. Epub 2016 Nov 4. link to original article contains protocol PubMed
Paclitaxel, nanoparticle albumin-bound & Bevacizumab
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Example orders
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Robert et al. 2011 (RIBBON-1) | Phase III | nab-Paclitaxel | Superior PFS |
Brufsky et al. 2011 (RIBBON-2) | Phase III | nab-Paclitaxel | Superior PFS |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Vinorelbine & Bevacizumab
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Example orders
Regimen #1, vinorelbine 25 mg/m2 weekly
Study | Evidence |
---|---|
Burstein et al. 2008 | Phase II |
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV once per week
- Bevacizumab (Avastin) 10 mg/kg IV once every other week
Given until progression of disease or unacceptable toxicity
Regimen #2, vinorelbine 30 mg/m2 q3wk
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Brufsky et al. 2011 (RIBBON-2) | Phase III | Vinorelbine | Superior PFS |
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once on day 1
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Burstein HJ, Chen YH, Parker LM, Savoie J, Younger J, Kuter I, Ryan PD, Garber JE, Chen H, Campos SM, Shulman LN, Harris LN, Gelman R, Winer EP. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin Cancer Res. 2008 Dec 1;14(23):7871-7. link to original article contains verified protocol PubMed
- Brufsky AM, Hurvitz S, Perez E, Swamy R, Valero V, O'Neill V, Rugo HS. RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2011 Nov 10;29(32):4286-93. Epub 2011 Oct 11. link to original article contains verified protocol PubMed
Metastatic disease, maintenance after first-line therapy
Bevacizumab monotherapy
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FEC & Bevacizumab: Fluorouracil, Epirubicin, Cyclophosphamide, Bevacizumab
Regimen
Study | Evidence |
---|---|
Robert et al. 2011 (RIBBON-1) | Non-randomized portion of RCT |
Preceding treatment
Chemotherapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, Perez EA, Yardley DA, Chan SY, Zhou X, Phan SC, O'Shaughnessy J. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. Epub 2011 Mar 7. link to original article contains verified protocol PubMed
Additional resources
- Gail model Breast Cancer Risk Assessment Tool
- Breast cancer BRCA1/BRCA2 genetic testing
- Adjuvant! Online (requires login)
- My Cancer Genome