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The purpose of this page is to capture information about complex comparisons that is not easily conveyed on the treatment regimen pages. Many complex multipart RCTs are of the "Y-shaped" format "A followed by B1 versus B2" or "A1 versus A2 followed by B" and this can be captured on the treatment regimen pages. This page will convey information on more complicated designs, such as "A followed by B versus B followed by A" or "A followed by B versus C followed by D".

Acute myeloid leukemia

COG AAML0531

To be completed

References

Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. link to original article link to PMC article PubMed

UK MRC AML12

To be completed

References

Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. link to original article PubMed

UK MRC AML15

To be completed

References

Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. link to original article PubMed

Acute promyelocytic leukemia

C9710

Note: this trial included a second randomization during the maintenance phase, which is not complex and is therefore not reported here.

Arm 1

ATRA, Cytarabine, Daunorubicin, then ATRA & Daunorubicin

Arm 2, with ATO3

ATRA, Cytarabine, Daunorubicin, then arsenic trioxide, then ATRA & Daunorubicin

Comparative efficacy

Regimen	Efficacy
Without ATO3	Inferior EFS
With ATO3	Superior EFS

References

Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains dosing details in manuscript link to PMC article PubMed

Breast cancer

DBCG 82b

Arm 1 (Experimental)

Mastectomy, then CMF x 1, then radiotherapy, then CMF x 7

Arm 2 (Control)

Mastectomy, then CMF x 9

Comparative efficacy

Regimen	Efficacy
With RT	Superior OS
Without RT	Inferior OS

References

Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. link to original article PubMed

Loesch et al. 2010

Arm 1, control

Surgery, then AC x 4, then T (Taxol) x 4

Arm 2, experimental

Surgery, then AT (Taxol) x 4, then wP x 12

Comparative efficacy

Regimen	Efficacy
AC-P	Seems not superior
AP-WP	Seems not superior

References

Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. link to original article PubMed

Mavroudis et al. 2017

Arm 1, sequential

Surgery, then Epirubicin, then Docetaxel

Arm 2, concurrent

Surgery, then Docetaxel & Epirubicin

Comparative efficacy

Schedule	Efficacy
Sequential	Might have superior DFS
Concurrent	Might have inferior DFS

References

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 article contains dosing details in manuscript link to PMC article PubMed

NeoALTTO

Arm 1, trastuzumab (C)

Trastuzumab x 6 wk, then TH (Paclitaxel) x 12 wk, then surgery, then FEC x 3, then Trastuzumab x 34 wk

Arm 1, lapatinib (E)

Lapatinib x 6 wk, then TL (Taxol) x 12 wk, then surgery, then FEC x 3, then Lapatinib x 34 wk

Arm 3, lapatinib & trastuzumab (E)

Lapatinib & Trastuzumab x 6 wk, then THL (Taxol) x 12 wk, then surgery, then FEC x 3, then Lapatinib & Trastuzumab x 34 wk

Comparative efficacy

The primary endpoint was pathologic complete response (pCR) rate. Comparison was only between experimental and control arms (i.e., 2 comparisons).

Backbone	Efficacy
Trastuzumab vs. Lapatinib	Seems not superior
Trastuzumab vs. Lapatinib & Trastuzumab	Inferior pCR rate
Lapatinib vs. Trastuzumab	Seems not superior
Lapatinib & Trastuzumab vs. Trastuzumab	Superior pCR rate

References

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 dosing details in manuscript PubMed
1. 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

NOAH

Arm 1, no trastuzumab (Control)

AT (Taxol) x 3, then T (Taxol) x 3, then CMF x 3, then surgery

Arm 2, with trastuzumab (Experimental)

ATH (Paclitaxel) x 3, then TH x 3, then CMF & H x 3, then surgery, then trastuzumab for a total of 1 year

Comparative efficacy

Sequencing	Efficacy
With trastuzumab	Seems to have superior EFS
No trastuzumab	Seems to have inferior EFS

References

Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. link to original article PubMed
1. Update: Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. link to original article PubMed

PREPARE

Arm 1, control

EC x 4, then T (Taxol) x 4, then surgery

Arm 2, experimental

ddE x 3, then ddT (Taxol) x 3, then CMF x 3, then surgery

Comparative efficacy

Regimen	Efficacy
Control	Seems not superior
Experimental	Seems not superior

References

Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. link to original article PubMed

Recht et al. 1996

Arm 1, chemo first

Lumpectomy, then CAMFP, then RT

Arm 2, RT first

Lumpectomy, then RT, then CAMFP

Comparative efficacy

anti-HER2 medication	Comparative Efficacy
Chemo first	Seems to have superior MFS
RT first	Seems to have inferior MFS

References

Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. link to original article PubMed

SBG 9401

Arm 1 (control)

Surgery, then FEC x 2, then HD-FEC x 1, then CTCb with auto HSCT

Arm 2 (experimental)

Tailored FEC x 6

Comparative efficacy

Regimen	Efficacy
Control	Seems to have inferior RFS
Experimental	Seems to have superior RFS

References

Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. link to original article PubMed

SWOG-8814

Arm 1 (Control)

Surgery, then tamoxifen x 5 y

Arm 2, CAF-T (Experimental)

Surgery, then CAF x 6, then tamoxifen x 5 y

Arm 3, CAFT (Experimental)

Surgery, then CAFT

Comparative efficacy

Comparison 1

Design	Efficacy
No chemotherapy	Might have inferior OS
With chemotherapy	Might have superior OS

Comparison 2

Timing	Efficacy
Concurrent (CAFT)	Might have inferior DFS
Sequential (CAF-T)	Might have superior DFS

References

Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. link to original article link to PMC article PubMed

TRYPHAENA

Arm A

FEC & HP x 3, then THP x 3, then surgery

Arm B

FEC x 3, then THP x 3, then surgery

Arm C

TCHP x 6, then surgery

Comparative efficacy

Note: this was a cardiac safety study; efficacy findings are not reported.

References

Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. link to original article PubMed

Cervical cancer

NOGGO-AGO

Arm 1 (Control)

Surgery, then adjuvant Carboplatin & Ifosfamide x 4, then EBRT

Arm 2 (Experimental)

Surgery, then adjuvant Carboplatin, Ifosfamide, Erythropoietin alfa, then EBRT & Erythropoietin alfa

Comparative efficacy

Regimen	Efficacy
No EPO	Might have inferior RFS
With EPO	Might have superior RFS

References

Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. link to original article PubMed

Colorectal cancer

CAIRO

Arm 1, sequential single agent (Control)

First-line capecitabine, then second-line irinotecan, then third-line CapeOx

Arm 2, sequential combinations (Experimental)

First-line CAPIRI, then second-line CapeOx

Comparative efficacy

Approach	Efficacy
Sequential single agent	Seems not superior
Sequential combinations	Seems not superior

References

Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Loosveld OJ, van Bochove A, Sinnige HA, Creemers GM, Tesselaar ME, Slee PHTJ, Werter MJ, Mol L, Dalesio O, Punt CJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007 Jul 14;370(9582):135-142. link to original article PubMed

FFCD 2000-05

Arm 1, sequential (Control)

First-line sLV5FU2, then second-line mFOLFOX6, then third-line FOLFIRI

Arm 2, combination (Experimental)

First-line mFOLFOX6, then second-line FOLFIRI

Comparative efficacy

Approach	Efficacy	Toxicity
Sequential	Seems not superior	Less toxic
Combination	Seems not superior	More toxic

References

Ducreux M, Malka D, Mendiboure J, Etienne PL, Texereau P, Auby D, Rougier P, Gasmi M, Castaing M, Abbas M, Michel P, Gargot D, Azzedine A, Lombard-Bohas C, Geoffroy P, Denis B, Pignon JP, Bedenne L, Bouché O; Fédération Francophone de Cancérologie Digestive (FFCD) 2000–05 Collaborative Group. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial. Lancet Oncol. 2011 Oct;12(11):1032-44. Epub 2011 Sep 6. link to original article PubMed

Diffuse large B-cell lymphoma

SWOG S8736

Arm 1 - Control

CHOP x 8

Arm 2 - Experimental

CHOP x 3, then RT x 40 to 5500 cGy

Comparative efficacy

Regimen	Efficacy
CHOP x 8	Seems to have inferior OS
CHOP x 3, then RT	Seems to have superior OS

References

Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. link to original article PubMed

Endometrial cancer

PORTEC-3

Arm 1 - Control

Surgery, then RT

Arm 2 - Experimental

Surgery, then Cisplatin & RT, then Carboplatin & Paclitaxel

Comparative efficacy

Modality	Efficacy
Radiotherapy	Seems to have inferior OS¹
Chemoradiotherapy	Seems to have superior OS¹

¹Reported efficacy is based on the 2019 update.

References

de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. link to original article link to PMC article PubMed
1. Update: de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. link to original article PubMed

Follicular lymphoma

GALLIUM

Arm 1 - Control

BR x 6 or R-CHOP x 8 or R-CVP x 8, then Rituximab maintenance x 2 y

Arm 2 - Experimental

Bendamustine & Obinutuzumab x 6 or G-CHOP x 8 or G-CVP x 8, then Obinutuzumab maintenance x 2y

Comparative efficacy

mAb	Efficacy	Toxicity
Rituximab-chemotherapy	Inferior PFS	Superior toxicity
Obinutuzumab-chemotherapy	Superior PFS (primary endpoint) PFS36: 80% vs 73% (HR 0.66, 95% CI 0.51-0.85)	Inferior toxicity

References

Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. link to original article link to appendix PubMed

Gastroesophageal cancer

POET

Arm 1

PLF x 15 wk, then surgery

Arm 2

PLF x 12 wk, then Cisplatin, Etoposide, RT, then surgery

Comparative efficacy

Regimen	Efficacy
Neoadjuvant chemotherapy only	Might have inferior OS
Neoadjuvant chemotherapy and chemoradiotherapy	Might have superior OS

References

Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article PubMed

PRODIGE5/ACCORD17

Arm 1 - Control

Definitive CF & RT, then CF x 2

Arm 2 - Experimental

Definitive FOLFOX4 & RT, then FOLFOX4 x 3

Comparative efficacy

Regimen	Efficacy
CF-based	Seems not superior
FOLFOX4-based	Seems not superior

References

Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article PubMed

Glioblastoma

AVAglio

Arm 1, control

Surgery, then adjuvant temozolomide & RT, then temozolomide maintenance

Arm 2, experimental

Surgery, then adjuvant temozolomide, bevacizumab, RT, then temozolomide & bevacizumab maintenance, then bevacizumab maintenance

Comparative efficacy

Regimen	Efficacy
Temozolomide alone	Inferior PFS
Bevacizumab-containing arm	Superior PFS

References

Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. link to original article PubMed

EORTC 22981/26981; NCIC-CTG CE.3

Arm 1, control

Surgery, then adjuvant radiotherapy

Arm 2, experimental

Surgery, then adjuvant Temozolomide & RT, then Temozolomide maintenance

Comparative efficacy

Regimen	Efficacy
Radiotherapy alone	Inferior OS
Temozolomide-containing arm	Superior OS

References

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; EORTC Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. link to original article PubMed

RTOG 0825

Arm 1, control

Surgery, then adjuvant Temozolomide & RT, then Temozolomide maintenance

Arm 2, experimental

Surgery, then adjuvant Temozolomide, Bevacizumab, RT, then Temozolomide & Bevacizumab maintenance

Comparative efficacy

Note: although the control regimen had inferior PFS, the effect size did not reach the prespecified improvement target.

Regimen	Efficacy
Temozolomide alone	Inferior PFS
Bevacizumab-containing arm	Superior PFS (co-primary endpoint)

References

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. link to original article link to PMC article PubMed

Head and neck cancer

EORTC 24954

Arm 1, control

CF x 4, then RT

Arm 2, experimental

CF/RT

Comparative efficacy

Regimen	Efficacy
Sequential RT	Seems not superior
Alternating RT	Seems not superior

References

Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; EORTC Head and Neck Cancer Cooperative Group; EORTC Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27. link to original article link to PMC article PubMed

RTOG 91-11

Arm 1, induction chemotherapy, then radiotherapy (Control)

PF x 3, then RT

Arm 2, concurrent chemoradiotherapy (Experimental)

Cisplatin & RT

Arm 3, radiotherapy (Experimental)

RT

Comparative efficacy

Efficacy is based on the 2012 update.

Regimen vs.	Arm 1	Arm 2	Arm 3
Arm 1 vs.		Inferior LFS	Seems to have superior LFS
Arm 2 vs.	Superior LFS		Seems to have superior LFS
Arm 3 vs.	Seems to have inferior LFS	Seems to have inferior LFS

References

Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. link to original article PubMed
1. Update: Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. link to original article contains partial protocol link to PMC article PubMed

Classical Hodgkin lymphoma

EORTC-GELA H8-F

Arm 1

MOPP-ABV x 3, then IFRT

Arm 2

STNI

Comparative efficacy

Regimen	Efficacy
MOPP-ABV x 3, then IFRT	Superior OS
STNI	Inferior OS

References

Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC; GELA. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains dosing details in supplement PubMed

EORTC-GELA H8-U

Comparative efficacy

Note: the paper describes this as an equivalence study, although the primary endpoint of EFS had p=0.80.

Regimen	Efficacy
MOPP-ABV x 4, then IFRT	Inconclusive whether equivalent
MOPP-ABV x 4, then STNI	Inconclusive whether equivalent
MOPP-ABV x 6, then IFRT	Inconclusive whether equivalent

References

Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains dosing details in supplement PubMed

EORTC/LYSA/FIL H10

Note: randomization in this trial occurred before treatment, but took effect after 2 cycles of ABVD, and only if interim PET-CT was negative.

Arm 1

Favorable: ABVD x 4
Unfavorable: ABVD x 6

Arm 2

Favorable: ABVD x 3, then INRT
Unfavorable: ABVD x 4, then INRT

Comparative efficacy

Regimen	Efficacy
ABVD x 4	Inconclusive whether non-inferior
ABVD x 3, then INRT	Inconclusive whether non-inferior

References

Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article PubMed
1. Update: André MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, Casasnovas O, Brice P, van der Maazen R, Re A, Edeline V, Fermé C, van Imhoff G, Merli F, Bouabdallah R, Sebban C, Specht L, Stamatoullas A, Delarue R, Fiaccadori V, Bellei M, Raveloarivahy T, Versari A, Hutchings M, Meignan M, Raemaekers J. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017 Jun 1;35(16):1786-1794. Epub 2017 Mar 14. link to original article PubMed

GHSG HD17

Arm 1 (Control)

eBEACOPP x 2, then ABVD x 2, then IFRT x 3000 cGy

Arm 2 (Experimental)

PET4 positive: eBEACOPP x 2, then ABVD x 2, then IFRT x 3000 cGy
PET4 negative: eBEACOPP x 2, then ABVD x 2

Comparative efficacy

Chemotherapy	Efficacy
2+2 -> IFRT	Non-inferior PFS
PET-guided therapy	Non-inferior PFS

References

Borchmann P, Plütschow A, Kobe C, Greil R, Meissner J, Topp MS, Ostermann H, Dierlamm J, Mohm J, Thiemer J, Sökler M, Kerkhoff A, Ahlborn M, Halbsguth TV, Martin S, Keller U, Balabanov S, Pabst T, Vogelhuber M, Hüttmann A, Wilhelm M, Zijlstra JM, Moccia A, Kuhnert G, Bröckelmann PJ, von Tresckow B, Fuchs M, Klimm B, Rosenwald A, Eich H, Baues C, Marnitz S, Hallek M, Diehl V, Dietlein M, Engert A. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):223-234. link to original article PubMed NCT01356680

NCIC-CTG/ECOG HD.6

Note: this randomization was for patients with unfavorable risk.

Arm 1

ABVD x 4

Arm 2

ABVD x 2, then STNI

Comparative efficacy

Efficacy is based on the 2011 update.

Regimen	Efficacy
ABVD x 4	Seems to have superior OS
ABVD x 2, then STNI	Seems to have inferior OS

References

Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, Burns BF, Winter JN, Horning SJ, Dar AR, Djurfeldt MS, Ding K, Shepherd LE; National Cancer Institute of Canada Clinical Trials Group; ECOG. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 Jul 20;23(21):4634-42. Epub 2005 Apr 18. link to original article PubMed
1. Update: Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; ECOG. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article PubMed

Mantle cell lymphoma

MCL Younger

Arm 1 (Control)

R-CHOP x 6, then Dexa-BEAM, then Cy/TBI auto HSCT

Arm 2 (Experimental)

R-CHOP/R-DHAP x 6, then cytarabine, melphalan, TBI auto HSCT

Comparative efficacy

Regimen	Efficacy
SOC	Seems to have inferior TTTF
Cytarabine-based	Seems to have superior TTTF

References

Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. link to original article PubMed
1. Update: Hermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, Pott C, Salles G, Feugier P, Hübel K, Haioun C, Casasnovas RO, Schmidt C, Bouabdallah K, Ribrag V, Kanz L, Dürig J, Metzner B, Sibon D, Cheminant M, Burroni B, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Dreyling M; European Mantle Cell Lymphoma Network. High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023 Jan 20;41(3):479-484. Epub 2022 Dec 5. link to original article PubMed

Multiple myeloma

HOVON-50

Arm 1 (Control)

VAD, then CAD & G-CSF stem cell mobilization, then single or tandem melphalan auto HSCT, then interferon alfa maintenance

Arm 2 (Experimental)

TAD x 3, then CAD & G-CSF stem cell mobilization, then single or tandem melphalan auto HSCT, then thalidomide maintenance

Comparative efficacy

Regimen	Efficacy
SOC	Inferior PFS
Thalidomide-based	Superior PFS

References

Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. link to original article PubMed
1. Update: van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. link to original article PubMed

Non-small cell lung cancer

ECOG 3598

Arm 1 (Control)

PC induction, then Carboplatin, Paclitaxel, RT

Arm 2, with thalidomide (Experimental)

TPC, then Carboplatin, Paclitaxel, Thalidomide, RT

Comparative efficacy

Regimen	Efficacy
Without thalidomide	Seems not superior
With thalidomide	Seems not superior

References

Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. link to original article link to PMC article PubMed

IUNO

Arm 1, "early" erlotinib

Maintenance erlotinib

Arm 2, "late" erlotinib

Placebo until progression or intolerance, then erlotinib

Comparative efficacy

Timing	Efficacy
Maintenance erlotinib	Did not meet primary endpoint of OS
Second-line erlotinib	Did not meet primary endpoint of OS

References

Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article contains dosing details in manuscript PubMed

RTOG 9410

Arm 1, sequential (control)

Cisplatin & Vinblastine, then RT

Arm 2, concurrent (experimental)

Cisplatin, Etoposide, RT

Arm 3, concurrent (experimental)

Cisplatin, Vinblastine, RT

Comparative efficacy

Schedule	Efficacy
Concurrent	Seems to have superior OS
Sequential	Seems to have inferior OS

References

Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article PubMed

Ovarian cancer

GOG 114

Arm 1 - Control

Cisplatin & Paclitaxel x 6

Arm 2 - Experimental

Carboplatin AUC 9 x 2, then IP Cisplatin & IV Paclitaxel x 6

Comparative efficacy

Regimen	Efficacy
Control	Seems to have inferior OS
Experimental	Seems to have superior OS

References

Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. link to original article PubMed

Pancreatic cancer

GERCOR LAP07

This study had two randomizations; the second only occurred if patients were progression-free after 4 cycles.

Arm 1 - Control

Gemcitabine x 6

Arm 2 - Experimental

Gemcitabine x 4, then Capecitabine & RT

Arm 3 - Experimental

Erlotinib & Gemcitabine x 6

Arm 4 - Experimental

Erlotinib & Gemcitabine x 4, then Capecitabine, Erlotinib, RT

Comparative efficacy

First randomization

Regimen	Efficacy
Gemcitabine	Might have superior OS
With Erlotinib	Might have inferior OS

Second randomization

Modality	Efficacy
Chemotherapy	Seems not superior
Chemoradiotherapy	Seems not superior

References

Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. link to original article PubMed

Rectal cancer

CinClare

Arm 1 (Control)

Capecitabine & RT, then CapeOx x 1, then TME, then CapeOx x 5

Arm 2 (Experimental)

Genotype-dosed CAPIRI & RT, then genotype-dosed CAPIRI x 1, then TME, then CapeOx x 5

Comparative efficacy

Regimen	Efficacy
Control	Inferior pCR rate
Experimental	Superior pCR rate

References

Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. link to original article link to PMC article PubMed NCT02605265

RAPIDO

Arm 1 (Control)

Capecitabine & RT, then TME, then (per hospital policy) CapeOx x 8 or FOLFOX4 x 12

Arm 2 (Experimental)

RT, then CapeOx x 6 or FOLFOX4 x 9, then TME

Comparative efficacy

Regimen	Efficacy
RT, then chemo, then TME	Seems to have superior DRTF
Chemo-RT, then TME, +/- adjuvant chemo	Seems to have inferior DRTF

References

Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. link to original article PubMed

@@ Line 1: / Line 1: @@
-The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Breast_cancer|main breast cancer page]] for current regimens.
+<span id="BackToTop"></span>
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-{| class="wikitable" style="float:right; margin-right: 5px;"
+[[#top|Back to Top]]
-|-
+</div>
-|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
+The purpose of this page is to capture information about complex comparisons that is not easily conveyed on the treatment regimen pages. Many complex multipart RCTs are of the "Y-shaped" format "A followed by B1 versus B2" or "A1 versus A2 followed by B" and this can be captured on the treatment regimen pages. This page will convey information on more complicated designs, such as "A followed by B versus B followed by A" or "A followed by B versus C followed by D".
-<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
-|}
 {{TOC limit|limit=3}}
-=Neoadjuvant therapy=
+=[[Acute myeloid leukemia]]=
-==CVAP {{#subobject:4a01b8|Regimen=1}}==
+==COG AAML0531==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CVAP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin),  '''<u>P</u>'''rednisolone
-<br>VACP: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisolone
-===Regimen {{#subobject:7b4b85|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2002.20.6.1456 Smith et al. 2002]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2004.05.207 Thomas E et al. 2004]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-|-
-|}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Vincristine (Oncovin)]]
-*[[Doxorubicin (Adriamycin)]]
-====Hormonotherapy====
-*[[Prednisolone (Millipred)]]
-====Subsequent treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-===References===
-# Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol. 2002 Mar 15;20(6):1456-66. [https://ascopubs.org/doi/full/10.1200/JCO.2002.20.6.1456 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11896092 PubMed]
-# Thomas E, Holmes FA, Smith TL, Buzdar AU, Frye DK, Fraschini G, Singletary SE, Theriault RL, McNeese MD, Ames F, Walters R, Hortobagyi GN. The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial. J Clin Oncol. 2004 Jun 15;22(12):2294-302. [https://ascopubs.org/doi/full/10.1200/JCO.2004.05.207 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15197190 PubMed]
-==Epirubicin monotherapy {{#subobject:c54ed1|Regimen=1}}==
+To be completed
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:21c010|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://erc.bioscientifica.com/view/journals/erc/12/2/0120383.xml Bottini et al. 2005]
-| style="background-color:#1a9851" |Phase III (C)
-|Epirubicin & Tamoxifen
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Chemotherapy====
-*[[Epirubicin (Ellence)]]
-====Subsequent treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
 ===References===
-# Bottini A, Berruti A, Brizzi MP, Bersiga A, Generali D, Allevi G, Aguggini S, Bolsi G, Bonardi S, Tondelli B, Vana F, Tampellini M, Alquati P, Dogliotti L. Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial. Endocr Relat Cancer. 2005 Jun;12(2):383-92. [https://erc.bioscientifica.com/view/journals/erc/12/2/0120383.xml link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15947110 PubMed]
+# Gamis AS, Alonzo TA, Meshinchi S, Sung L, Gerbing RB, Raimondi SC, Hirsch BA, Kahwash SB, Heerema-McKenney A, Winter L, Glick K, Davies SM, Byron P, Smith FO, Aplenc R. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014 Sep 20;32(27):3021-32. [https://doi.org/10.1200/JCO.2014.55.3628 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162498/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25092781/ PubMed]
-=Adjuvant therapy=
+==UK MRC AML12==
-==ACT {{#subobject:4a01b8|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ACT: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''amoxifen
-===Regimen {{#subobject:7b4b85|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
-|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[#PFT|PFT]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://link.springer.com/article/10.1007%2Fs10147-013-0657-z Shien et al. 2014 (JCOG9401)]
-|style="background-color:#1a9851" |Phase III (E-esc)
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
-| style="background-color:#91cf60" |Seems to have superior RFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143604/ Shien et al. 2014 (JCOG9404)]
-|style="background-color:#1a9851" |Phase III (E-de-esc)
-|TUFT
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-====Hormonotherapy====
-*[[Tamoxifen (Nolvadex)]]
-===References===
-# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2189950 PubMed]
-## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://ascopubs.org/doi/full/10.1200/JCO.2004.01.042 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15452182 PubMed]
-# '''JCOG9401:''' Shien T, Iwata H, Aogi K, Fukutomi T, Inoue K, Kinoshita T, Takahashi M, Matsui A, Shibata T, Fukuda H. Tamoxifen versus tamoxifen plus doxorubicin and cyclophosphamide as adjuvant therapy for node-positive postmenopausal breast cancer: results of a Japan Clinical Oncology Group Study (JCOG9401). Int J Clin Oncol. 2014 Dec;19(6):982-8. Epub 2014 Jan 7. [https://link.springer.com/article/10.1007%2Fs10147-013-0657-z link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24395447 PubMed]
-# '''JCOG9404:''' Shien T, Iwata H, Fukutomi T, Inoue K, Aogi K, Kinoshita T, Ando J, Takashima S, Nakamura K, Shibata T, Fukuda H. Tamoxifen plus tegafur-uracil (TUFT) versus tamoxifen plus Adriamycin (doxorubicin) and cyclophosphamide (ACT) as adjuvant therapy to treat node-positive premenopausal breast cancer (PreMBC): results of Japan Clinical Oncology Group Study 9404. Cancer Chemother Pharmacol. 2014 Sep;74(3):603-9. Epub 2014 Jul 24. [https://link.springer.com/article/10.1007%2Fs00280-014-2545-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143604/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25055938 PubMed]
-==AVCF {{#subobject:4a0878|Regimen=1}}==
+To be completed
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-AVCF: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:7b4c73|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.4.1136 Misset et al. 1996 (OncoFrance)]
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
-|[[Breast_cancer#CMF|CMF]]
-| style="background-color:#1a9850" |Superior OS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]]
-*[[Vincristine (Oncovin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Fluorouracil (5-FU)]]
-===References===
-# '''OncoFrance:''' Misset JL, di Palma M, Delgado M, Plagne R, Chollet P, Fumoleau P, Le Mevel B, Belpomme D, Guerrin J, Fargeot P, Metz R, Ithzaki M, Hill C, Mathé G. Adjuvant treatment of node-positive breast cancer with cyclophosphamide, doxorubicin, fluorouracil, and vincristine versus cyclophosphamide, methotrexate, and fluorouracil: final report after a 16-year median follow-up duration. J Clin Oncol. 1996 Apr;14(4):1136-45. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.4.1136 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8648368 PubMed]
-==AV-CMF {{#subobject:4a3928|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-AV-CMF: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''inblastine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:7bcju3|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.karger.com/Article/PDF/69831 Ploner et al. 2003 (ABCSG 3)]
-| style="background-color:#1a9851" |Randomized (E-RT-esc)
-|[[Breast_cancer#CMF|CMF]]
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Doxorubicin (Adriamycin)]]
-*[[Vinblastine (Velban)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
 ===References===
-# '''ABCSG 3:''' Ploner F, Jakesz R, Hausmaninger H, Kolb R, Stierer M, Fridrik M, Steindorfer P, Gnant M, Haider K, Mlineritsch B, Tschurtschenthaler G, Steger G, Seifert M, Kubista E, Samonigg H; Austrian Breast And Colorectal Cancer Study Group. Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients. Onkologie. 2003 Apr;26(2):115-9. [https://www.karger.com/Article/PDF/69831 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12771518 PubMed]
+# Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. [https://doi.org/10.1182/blood.V93.12.4131 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10361110/ PubMed]
-==CAMFP {{#subobject:4a01b8|Regimen=1}}==
+==UK MRC AML15==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CAMFP: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
-===Regimen {{#subobject:7b4b85|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM199605233342102 Recht et al. 1996]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[Complex_multipart_regimens#Recht_et_al._1996|See link]]
-|[[Complex_multipart_regimens#Recht_et_al._1996|See link]]
-|-
-|}
-''Note: this was a trial examining sequencing of chemotherapy and radiotherapy; see text for efficacy details.''
-====Preceding treatment====
-*[[Surgery#Lumpectomy|Lumpectomy]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
-'''21-day cycle for 4 cycles'''
+To be completed
 ===References===
-# Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. [https://www.nejm.org/doi/full/10.1056/NEJM199605233342102 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8614420 PubMed]
+# Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891/ PubMed]
-==CEF/CMF {{#subobject:682333|Regimen=1}}==
+=[[Acute promyelocytic leukemia]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==C9710==
-|-
-|[[#top|back to top]]
-|}
-CEF/CMF: '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>F</u>'''luorouracil alternating with '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:3d1971|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202939/ Bedognetti et al. 2011]
-| style="background-color:#1a9851" |Phase III (C)
-|CEFT/CMFT
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy, CEF portion====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Epirubicin (Ellence)]]
-*[[Fluorouracil (5-FU)]]
-====Chemotherapy, CMF portion====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-===References===
-# Bedognetti D, Sertoli MR, Pronzato P, Del Mastro L, Venturini M, Taveggia P, Zanardi E, Siffredi G, Pastorino S, Queirolo P, Gardin G, Wang E, Monzeglio C, Boccardo F, Bruzzi P. Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial. J Natl Cancer Inst. 2011 Oct 19;103(20):1529-39. Epub 2011 Sep 15. [https://academic.oup.com/jnci/article/103/20/1529/905862 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202939/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21921285 PubMed]
-==CFP {{#subobject:b514cd|Regimen=1}}==
+''Note: this trial included a second randomization during the maintenance phase, which is not complex and is therefore not reported here.''
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Arm 1===
-|-
+*[[Acute_promyelocytic_leukemia#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]], then [[Acute_promyelocytic_leukemia#ATRA_.26_Daunorubicin_2|ATRA & Daunorubicin]]
-|[[#top|back to top]]
+===Arm 2, with ATO3===
-|}
+*[[Acute_promyelocytic_leukemia#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]], then [[Acute_promyelocytic_leukemia#Arsenic_trioxide_monotherapy_2|arsenic trioxide]], then [[Acute_promyelocytic_leukemia#ATRA_.26_Daunorubicin_2|ATRA & Daunorubicin]]
-CFP: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
+===Comparative efficacy===
-===Regimen {{#subobject:3b8f7d|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="width: 100%; text-align:center;"
+!'''Regimen'''
-!style="width: 25%"|Study
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)90678-5/fulltext Ahmann et al. 1978]
+|Without ATO3
-|style="background-color:#1a9851" |Phase III (E-esc)
+|style="background-color:#d73027"|Inferior EFS
-|[[#Melphalan_monotherapy|Melphalan]]
-| style="background-color:#91cf60" |Seems to have superior OS
 |-
-|rowspan=2|[https://jamanetwork.com/journals/jama/article-abstract/370748 Caprini et al. 1980]
+|With ATO3
-|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
+|style="background-color:#1a9850"|Superior EFS
-|1. [[#Melphalan_monotherapy|Melphalan]]
-| style="background-color:#91cf60" |Seems to have superior DFS
-|-
-|2. CFP & BCG
-| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
 ===References===
-# Ahmann DL, Scanlon PW, Bisel HF, Edmonson JH, Frytak S, Payne WS, O'Fallon JR, Hahn RG, Ingle JN, O'Connell MJ, Rubin J. Repeated adjuvant chemotherapy with phenylalanine mustard or 5-fluorouracil, cyclophosphamide, and prednisone with or without radiation, after mastectomy for breast cancer. Lancet. 1978 Apr 29;1(8070):893-6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)90678-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/76842 PubMed]
+# Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [https://doi.org/10.1182/blood-2010-02-269621 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755/ PubMed]
-# Caprini JA, Oviedo MA, Cunningham MP, Cohen E, Trueheart RS, Khandekar JD, Scanlon EF. Adjuvant chemotherapy for stage II and III breast carcinoma. JAMA. 1980 Jul 18;244(3):243-6. [https://jamanetwork.com/journals/jama/article-abstract/370748 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6991733 PubMed]
-==CFP & Oophorectomy {{#subobject:ba429d|Regimen=1}}==
+=[[Breast cancer]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==DBCG 82b==
-|-
-|[[#top|back to top]]
-|}
-CFP & Oophorectomy: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone & Bilateral Oophorectomy
-===Regimen {{#subobject:26519a|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 Ahmann et al. 1977]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#Oophorectomy|Oophorectomy]]
-| style="background-color:#91cf60" |Seems to have superior PFS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
-*[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]]
-===References===
-# Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. [https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/876327 PubMed]
-==CMFL {{#subobject:1abd14|Regimen=1}}==
+===Arm 1 (Experimental)===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Mastectomy]], then [[Breast_cancer#CMF|CMF]] x 1, then radiotherapy, then [[Breast_cancer#CMF|CMF]] x 7
+===Arm 2 (Control)===
+*[[Mastectomy]], then [[Breast_cancer#CMF|CMF]] x 9
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|With RT
-|}
+| style="background-color:#1a9850" |Superior OS
-CMFL: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin (Folinic acid)
-===Regimen {{#subobject:3dbcd1|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 Goldhirsch et al. 1989 (LCBS V)]
+|Without RT
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#d73027" |Inferior OS
-|[[#Observation|No further treatment]]
-| style="background-color:#91cf60" |Seems to have superior DFS
 |-
 |}
-====Preceding treatment====
-*[[Surgery#Mastectomy|Mastectomy]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-*[[Folinic acid (Leucovorin)]]
-'''8-day course'''
 ===References===
-# '''LCBS V:''' Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644533 PubMed]
+# Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b trial. N Engl J Med. 1997 Oct 2;337(14):949-55. [https://doi.org/10.1056/NEJM199710023371401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9395428/ PubMed]
-==CMFP {{#subobject:527931|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CMFP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
-===Regimen {{#subobject:3feec0|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 Goldhirsch et al. 1988 (IBCSG V)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#CMFL|CMFL]] x 1
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 Mansour et al. 1989 (INT-0011)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#Observation|No further treatment]]
-| style="background-color:#1a9850" |Superior DFS
-|-
-|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract Tormey et al. 1990 (ECOG E5177)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[Breast_cancer#CMF|CMF]]<br> 2. [[#CMFPT|CMFPT]]
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
-'''28-day cycle for 6 to 12 cycles'''
-===References===
+==Loesch et al. 2010==
-# '''IBCSG V:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. [https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2901037 PubMed]
-# '''ECOG E1180:''' Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2915651 PubMed]
-## '''Update:''' Mansour EG, Eudey L, Tormey DC, Shatila AH, Osborne CK, Gilchrist KW, Cooper MR, Falkson G. Chemotherapy versus observation in high-risk node-negative breast cancer patients. J Natl Cancer Inst Monogr. 1992;(11):97-104. [https://www.ncbi.nlm.nih.gov/pubmed/1627437 PubMed]
-# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2403834 PubMed]
-==CMFPT {{#subobject:204d9d|Regimen=1}}==
+===Arm 1, control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Cyclophosphamide_.26_Doxorubicin_.28AC.29_2|AC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4
+===Arm 2, experimental===
+*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Doxorubicin_.26_Paclitaxel_.28AT.29|AT (Taxol)]] x 4, then [[#Paclitaxel_monotherapy.2C_weekly_2|wP]] x 12
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|AC-P
-|}
-CMFPT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone, '''<u>T</u>'''amoxifen
-===Regimen {{#subobject:3a762a|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
-|rowspan = 2 style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[#Observation|Observation]]
-| style="background-color:#1a9850" |Superior DFS
-|-
-|2. [[#PT|PT]]
-| style="background-color:#91cf60" |Seems to have superior DFS
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 Goldhirsch et al. 1988 (IBCSG V)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#CMFL|CMFL]] x 1
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract Tormey et al. 1990 (ECOG E5177)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[Breast_cancer#CMF|CMF]]<br> 2. CMFP
 | style="background-color:#ffffbf" |Seems not superior
 |-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.4.599 Falkson et al. 1990]
+|AP-WP
-| style="background-color:#1a9851" |Phase III (C)
-|CMFPT x 4
 | style="background-color:#ffffbf" |Seems not superior
 |-
 |}
-====Preceding treatment====
-*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
-*[[Tamoxifen (Nolvadex)]]
-'''28-day cycle for 6 to 12 cycles'''
 ===References===
-# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
+# Loesch D, Greco FA, Senzer NN, Burris HA, Hainsworth JD, Jones S, Vukelja SJ, Sandbach J, Holmes F, Sedlacek S, Pippen J, Lindquist D, McIntyre K, Blum JL, Modiano MR, Boehm KA, Zhan F, Asmar L, Robert N. Phase III multicenter trial of doxorubicin plus cyclophosphamide followed by paclitaxel compared with doxorubicin plus paclitaxel followed by weekly paclitaxel as adjuvant therapy for women with high-risk breast cancer. J Clin Oncol. 2010 Jun 20;28(18):2958-65. Epub 2010 May 17. [https://doi.org/10.1200/JCO.2009.24.1000 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20479419/ PubMed]
-# '''IBCSG V:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med. 1988 Sep 15;319(11):677-83. [https://www.nejm.org/doi/full/10.1056/NEJM198809153191104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2901037 PubMed]
-# '''ECOG E5177:''' Tormey DC, Gray R, Gilchrist K, Grage T, Carbone PP, Wolter J, Woll JE, Cummings FJ. Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. Cancer. 1990 Jan 15;65(2):200-6. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19900115)65:2%3C200::AID-CNCR2820650203%3E3.0.CO;2-Q/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2403834 PubMed]
-# Falkson HC, Gray R, Wolberg WH, Gillchrist KW, Harris JE, Tormey DC, Falkson G. Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study. J Clin Oncol. 1990 Apr;8(4):599-607. Erratum in: J Clin Oncol 1990 Sep;8(9):1603. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.4.599 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2179477 PubMed]
-==CMFT {{#subobject:204b9d|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CMFT: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
-===Regimen {{#subobject:3agt2a|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.surgjournal.com/article/0039-6060(80)90244-5/fulltext Hubay et al. 1980]
-| style="background-color:#1a9851" |Randomized (E-RT-esc)
-|CMF
-| style="background-color:#91cf60" |Seems to have superior RFS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Tamoxifen (Nolvadex)]]
-===References===
+==Mavroudis et al. 2017==
-# Hubay CA, Pearson OH, Marshall JS, Rhodes RS, Debanne SM, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Antiestrogen, cytotoxic chemotherapy, and bacillus Calmette-Guerin vaccination in stage II breast cancer: a preliminary report. Surgery. 1980 May;87(5):494-501. [https://www.surgjournal.com/article/0039-6060(80)90244-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7368100 PubMed]
-## '''Update:''' Hubay CA, Pearson OH, Marshall JS, Rhodes RS, DeBanne SM, Rosenblatt J, Mansour EG, Hermann RE, Jones JC, Flynn WJ, Eckert C, McGuire WL. Adjuvant chemotherapy, antiestrogen therapy and immunotherapy for stage II breast cancer: 45-month follow-up of a prospective, randomized clinical trial. Cancer. 1980 Dec 15;46(12 Suppl):2805-8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19801215)46:12%2B%3C2805::AID-CNCR2820461413%3E3.0.CO;2-H link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7004624 PubMed]
-==CMFVP {{#subobject:ae7a82|Regimen=1}}==
+===Arm 1, sequential===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#Epirubicin_monotherapy|Epirubicin]], then [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel]]
+===Arm 2, concurrent===
+*[[Surgery#Breast_cancer_surgery|Surgery]], then Docetaxel & Epirubicin
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Schedule'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Sequential
-|}
+|style="background-color:#d9ef8b"|Might have superior DFS
-CMFVP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
-===Regimen {{#subobject:538cb7|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 Hoogstraten et al. 1976]
-|style="background-color:#1a9851" |Phase III (E-esc)
-|[[Breast_cancer#Doxorubicin_monotherapy_3|Doxorubicin]]
-| style="background-color:#91cf60" |Seems to have superior ORR
-|-
-|[https://www.sciencedirect.com/science/article/pii/0014296480900377 Carmo-Pereira et al. 1980]
-|style="background-color:#1a9851" |Phase III (E-esc)
-|5-FU
-| style="background-color:#1a9850" |Superior OS
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O Glucksberg et al. 1982 (SWOG S7436)]
+|Concurrent
-|style="background-color:#1a9851" |Phase III (E-esc)
+|style="background-color:#fee08b"|Might have inferior DFS
-|[[#Melphalan_monotherapy|Melphalan]]
-| style="background-color:#1a9850" |Superior OS
-|-
-|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1983.1.2.138 Tormey et al. 1983a]
-|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
-|[[Breast_cancer#CMF|CMF]]
-| style="background-color:#1a9850" |Superior DFS
-|-
-|CMF-MER
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1993.11.9.1710 Rivkin et al. 1993 (SWOG S7827<sub>ER-</sub>)]
-|style="background-color:#1a9851" |Phase III (C)
-|CMFVP x 2 y
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1995.13.4.831 Budd et al. 1995 (SWOG S8313)]
-|style="background-color:#1a9851" |Phase III (C)
-|FAC-M
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.1.46 Rivkin et al. 1996 (SWOG S7821)]
-|style="background-color:#1a9851" |Phase III (C)
-|CMFVP & Oophorectomy
-| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-*[[Vincristine (Oncovin)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
 ===References===
-# Hoogstraten B, George SL, Samal B, Rivkin SE, Costanzi JJ, Bonnet JD, Thigpen T, Braine H. Combination chemotherapy and adriamycin in patients with advanced breast cancer: a Southwest Oncology Group study. Cancer. 1976 Jul;38(1):13-20. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197607)38:1%3C13::AID-CNCR2820380104%3E3.0.CO;2-5 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/947510 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. [https://doi.org/10.1038/bjc.2017.158 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584474/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28641315/ PubMed]
-# Carmo-Pereira J, Costa FO, Henriques E. Single-drug vs combination cytotoxic chemotherapy in advanced breast cancer: a randomized study. Eur J Cancer. 1980 Dec;16(12):1621-5. [https://www.sciencedirect.com/science/article/pii/0014296480900377 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/7014228 PubMed]
-# '''SWOG S7436:''' Glucksberg H, Rivkin SE, Rasmussen S, Tranum B, Gad-el-Mawla N, Costanzi J, Hoogstraten B, Athens J, Maloney T, McCracken J, Vaughn C. Combination chemotherapy (CMFVP) versus L-phenylalanine mustard (L-PAM) for operable breast cancer with positive axillary nodes: a Southwest Oncology Group Study. Cancer. 1982 Aug 1;50(3):423-34. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19820801)50:3%3C423::AID-CNCR2820500307%3E3.0.CO;2-O link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7046900 PubMed]
-## '''Update:''' Rivkin SE, Green SJ, Lew D, Costanzi JJ, Athens JW, Osborne CK, Vaughn CB, Martino S. Adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil, vincristine, and prednisone compared with single-agent L-phenylalanine mustard for patients with operable breast carcinoma and positive axillary lymph nodes: 20-year results of a Southwest Oncology Group study. Cancer. 2003 Jan 1;97(1):21-9. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.10982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12491501 PubMed]
-# Tormey DC, Weinberg VE, Holland JF, Weiss RB, Glidewell OJ, Perloff M, Falkson G, Falkson HC, Henry PH, Leone LA, Rafla S, Ginsberg SJ, Silver RT, Blom J, Carey RW, Schein PS, Lesnick GJ. A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer. J Clin Oncol. 1983 Feb;1(2):138-45. [https://ascopubs.org/doi/abs/10.1200/JCO.1983.1.2.138 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6366133 PubMed]
-# '''SWOG S7827:''' Rivkin SE, Green S, Metch B, Jewell WR, Costanzi JJ, Altman SJ, Minton JP, O'Bryan RM, Osborne CK. One versus 2 years of CMFVP adjuvant chemotherapy in axillary node-positive and estrogen receptor-negative patients: a Southwest Oncology Group study. J Clin Oncol. 1993 Sep;11(9):1710-6. [https://ascopubs.org/doi/abs/10.1200/JCO.1993.11.9.1710 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8355037 PubMed]
-# '''SWOG S8313:''' Budd GT, Green S, O'Bryan RM, Martino S, Abeloff MD, Rinehart JJ, Hahn R, Harris J, Tormey D, O'Sullivan J, Osborne CK. Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study. J Clin Oncol. 1995 Apr;13(4):831-9. [https://ascopubs.org/doi/abs/10.1200/JCO.1995.13.4.831 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7707108 PubMed]
-# '''SWOG S7821:''' Rivkin SE, Green S, O'Sullivan J, Cruz AB, Abeloff MD, Jewell WR, Costanzi JJ, Farrar WB, Osborne CK. Adjuvant CMFVP versus adjuvant CMFVP plus ovariectomy for premenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study. J Clin Oncol. 1996 Jan;14(1):46-51. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.1.46 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8558219 PubMed]
-==CPB {{#subobject:0d159a|Regimen=1}}==
+==NeoALTTO==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CPB: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''latinol (Cisplatin), '''<u>B</u>'''CNU (Carmustine)
-===Regimen {{#subobject:683965|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2005.10.202 Peters et al. 2005 (CALGB 9082)]
-| style="background-color:#1a9851" |Phase III (E-de-esc)
-|HD-CPB with auto HSCT
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-''Note: this trial is of important historic significance. Although neither arm was standard of care, the results established the non-value of high-dose therapy with autologous HSCT in the adjuvant treatment of breast cancer.''
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Cisplatin (Platinol)]]
-*[[Carmustine (BCNU)]]
-===References===
-# '''CALGB 9082:''' Peters WP, Rosner GL, Vredenburgh JJ, Shpall EJ, Crump M, Richardson PG, Schuster MW, Marks LB, Cirrincione C, Norton L, Henderson IC, Schilsky RL, Hurd DD. Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: a report of CALGB 9082, SWOG 9114, and NCIC MA-13. J Clin Oncol. 2005 Apr 1;23(10):2191-200. Epub 2005 Mar 14. [https://ascopubs.org/doi/full/10.1200/JCO.2005.10.202 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15767638 PubMed]
-==CTCb, then auto HSCT {{#subobject:7a4fec|Regimen=1}}==
+===Arm 1, trastuzumab (C)===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy|Trastuzumab]] x 6 wk, then [[Breast_cancer,_HER2-positive#Paclitaxel_.26_Trastuzumab_.28TH.29|TH (Paclitaxel)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|Trastuzumab]] x 34 wk
+===Arm 1, lapatinib (E)===
+*Lapatinib x 6 wk, then [[Breast_cancer,_HER2-positive#Lapatinib_.26_Paclitaxel_.28TL.29|TL (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then Lapatinib x 34 wk
+===Arm 3, lapatinib & trastuzumab (E)===
+*[[Breast_cancer,_HER2-positive#Lapatinib_.26_Trastuzumab|Lapatinib & Trastuzumab]] x 6 wk, then [[Breast_cancer,_HER2-positive#THL_.28Paclitaxel.29|THL (Taxol)]] x 12 wk, then [[surgery]], then [[Breast_cancer#FEC_2|FEC]] x 3, then [[Breast_cancer,_HER2-positive#Lapatinib_.26_Trastuzumab_2|Lapatinib & Trastuzumab]] x 34 wk
+===Comparative efficacy===
+''The primary endpoint was pathologic complete response (pCR) rate. Comparison was only between experimental and control arms (i.e., 2 comparisons).''
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Backbone'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Trastuzumab vs. Lapatinib
-|}
+|style="background-color:#ffffbf"|Seems not superior
-CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin
-<br>STAMP-V
-===Regimen {{#subobject:9d0c8a|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://jco.ascopubs.org/content/8/7/1239.long Eder et al. 1990]
+|Trastuzumab vs. Lapatinib & Trastuzumab
-| style="background-color:#91cf61" |Phase I/II
+|style="background-color:#d73027"|Inferior pCR rate
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)01350-6/fulltext Rodenhuis et al. 1998]
+|Lapatinib vs. Trastuzumab
-| style="background-color:#1a9851" |Randomized Phase II (E-esc)
+|style="background-color:#ffffbf"|Seems not superior
-|Standard adjuvant therapy
-| style="background-color:#ffffbf" |Seems not superior
 |-
-|[https://www.sciencedirect.com/science/article/pii/S0140673600028415 Bergh et al. 2000 (SBG 9401)]
+|Lapatinib & Trastuzumab vs. Trastuzumab
-| style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#1a9850"|Superior pCR rate
-|[[Complex_multipart_regimens#SBG_9401|See link]]
-| style="background-color:#fc8d59" |[[Complex_multipart_regimens#SBG_9401|See link]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa022794 Rodenhuis et al. 2003]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[Breast_cancer#FEC_2|FEC]] x 5
-| style="background-color:#d9ef8b" |Might have superior RFS
 |-
 |}
-''No longer used, but of historical interest.''
-====Preceding treatment====
-*Rodenhuis et al. 1998: [[Breast_cancer#FEC|Neoadjuvant FEC]] x 3, then [[Surgery#Breast_cancer_surgery|surgery]], then [[Breast_cancer#FEC_2|FEC]] x 1
-*Rodenhuis et al. 2003: [[Breast_cancer#FEC_2|FEC]] x 4
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup>/day on days -7 to -4
-*[[Thiotepa (Thioplex)]] 125 mg/m<sup>2</sup>/day on days -7 to -4
-*[[Carboplatin (Paraplatin)]] 200 mg/m<sup>2</sup>/day on days -7 to -4
-'''Stem cells re-infused on day 0'''
 ===References===
-# Eder JP, Elias A, Shea TC, Schryber SM, Teicher BA, Hunt M, Burke J, Siegel R, Schnipper LE, Frei E 3rd, Antman K. A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients. J Clin Oncol. 1990 Jul;8(7):1239-45. [http://jco.ascopubs.org/content/8/7/1239.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2162912 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. [https://doi.org/10.1016/S0140-6736(11)61847-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705192/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22257673/ PubMed]
-# Rodenhuis S, Richel DJ, van der Wall E, Schornagel JH, Baars JW, Koning CC, Peterse JL, Borger JH, Nooijen WJ, Bakx R, Dalesio O, Rutgers E. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998 Aug 15;352(9127):515-21. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(98)01350-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9716055 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. [https://doi.org/10.1016/S1470-2045(14)70320-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130998/ PubMed]
-# '''SBG 9401:''' Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. [https://www.sciencedirect.com/science/article/pii/S0140673600028415 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/11052580 PubMed]
-# Rodenhuis S, Bontenbal M, Beex LV, Wagstaff J, Richel DJ, Nooij MA, Voest EE, Hupperets P, van Tinteren H, Peterse HL, TenVergert EM, de Vries EG; Netherlands Working Party on Autologous Transplantation in Solid Tumors. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med. 2003 Jul 3;349(1):7-16. [https://www.nejm.org/doi/full/10.1056/NEJMoa022794 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12840087 PubMed]
-==Cyclophosphamide monotherapy {{#subobject:7b2fec|Regimen=1}}==
+==NOAH==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:9d3c8a|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025018/ Rubens et al. 1975]
-| style="background-color:#1a9851" |Phase III (C)
-|CMFV
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-===References===
-# Rubens RD, Knight RK, Hayward JL. Chemotherapy of advanced breast cancer: a controlled randomized trial of cyclophosphamide versus a four-drug combination. Br J Cancer. 1975 Dec;32(6):730-6. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2025018/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/766800 PubMed]
-# '''DBCG 77B:''' Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. [https://link.springer.com/article/10.1007/BF01806239 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6347278 PubMed]
-## '''Update:''' Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24969/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20186830 PubMed]
-==ECT, then auto HSCT {{#subobject:7a4gab|Regimen=1}}==
+===Arm 1, no trastuzumab (Control)===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*AT (Taxol) x 3, then T (Taxol) x 3, then CMF x 3, then [[surgery]]
+===Arm 2, with trastuzumab (Experimental)===
+*ATH (Paclitaxel) x 3, then [[Breast_cancer,_HER2-positive#Paclitaxel_.26_Trastuzumab_.28TH.29|TH]] x 3, then CMF & H x 3, then [[surgery]], then [[Breast_cancer,_HER2-positive#Trastuzumab_monotherapy_2|trastuzumab for a total of 1 year]]
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+|'''Sequencing'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|With trastuzumab
-|}
+|style="background-color:#91cf60"|Seems to have superior EFS
-ECT: '''<u>E</u>'''pirubicin, '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa
-===Regimen {{#subobject:9d0a2n|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)67784-7/fulltext Nitz et al. 2005 (WSG AM-01)]
+|No trastuzumab
-|style="background-color:#1a9851" |Phase III (E-esc)
+|style="background-color:#fc8d59"|Seems to have inferior EFS
-|[[Breast_cancer#ddEC|ddEC]] x 4, then ddCMF x 3
-| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
-''No longer used, but of historical interest.''
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Epirubicin (Ellence)]]
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Thiotepa (Thioplex)]]
 ===References===
-# '''WSG AM-01:''' Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, Werner C, Ziske C, Kirchner H, Metzner B, Souchon R, Ruffert U, Schütt G, Pollmanns A, Schmoll HJ, Middecke C, Baltzer J, Schrader I, Wiebringhaus H, Ko Y, Rösel S, Schwenzer T, Wernet P, Hinke A, Bender HG, Frick M; West German Study Group. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a multicentre phase III trial. Lancet. 2005 Dec 3;366(9501):1935-44. Erratum in: Lancet. 2006 Mar 4;367(9512):730. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)67784-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16325695 PubMed]
+# Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84. [https://doi.org/10.1016/S0140-6736(09)61964-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20113825/ PubMed]
+## '''Update:''' Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014 May;15(6):640-7. Epub 2014 Mar 20. Erratum in: Lancet Oncol. 2018 Dec;19(12):e667. [https://doi.org/10.1016/S1470-2045(14)70080-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24657003/ PubMed]
-==FAC & BCG {{#subobject:19f556|Regimen=1}}==
+==PREPARE==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-FAC & BCG: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, BCG
-===Regimen {{#subobject:08e709|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://jamanetwork.com/journals/jama/article-abstract/366766 Buzdar et al. 1979]
-| style="background-color:#91cf61" |Non-randomized
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
-====Immunotherapy====
-*[[Bacillus Calmette-Guérin (BCG)]]
-===References===
-# Buzdar AU, Blumenschein GR, Gutterman JU, Tashima CK, Hortobagyi GN, Smith TL, Campos LT, Wheeler WL, Hersh EM, Freireich EJ, Gehan EA. Postoperative adjuvant chemotherapy with fluorouracil, doxorubicin, cyclophosphamide, and BCG vaccine: a follow-up report. JAMA. 1979 Oct 5;242(14):1509-13. [https://jamanetwork.com/journals/jama/article-abstract/366766 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/470088 PubMed]
-==FNC {{#subobject:152c11|Regimen=1}}==
+===Arm 1, control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Breast_cancer#Cyclophosphamide_.26_Epirubicin_.28EC.29|EC]] x 4, then [[Breast_cancer_-_historical#Paclitaxel_monotherapy.2C_q3wk|T (Taxol)]] x 4, then [[Surgery#Breast_cancer_surgery|surgery]]
-|-
+===Arm 2, experimental===
-|[[#top|back to top]]
+*ddE x 3, then ddT (Taxol) x 3, then CMF x 3, then [[Surgery#Breast_cancer_surgery|surgery]]
-|}
+===Comparative efficacy===
-FNC: '''<u>F</u>'''luorouracil, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>C</u>'''yclophosphamide
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<br>CNF: '''<u>C</u>'''yclophosphamide, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>F</u>'''luorouracil
+!'''Regimen'''
-===Regimen {{#subobject:950f9d|Variant=1}}===
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://insights.ovid.com/pubmed?pmid=11474254 Ron et al. 2001]
+|Control
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[Breast_cancer#CMF|CMF]]
-| style="background-color:#91cf60" |Seems to have superior DFS
-|-
-|[https://insights.ovid.com/pubmed?pmid=14758135 Fountzilas et al. 2004 (HE 10/92)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
 | style="background-color:#ffffbf" |Seems not superior
 |-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2006.07.8576 Toledano et al. 2007 (ARCOSEIN)]
+|Experimental
-| style="background-color:#1a9851" |Phase III (C)
-|FNC & RT
 | style="background-color:#ffffbf" |Seems not superior
 |-
 |}
-====Preceding treatment====
+===References===
-*[[Surgery#Lumpectomy|Breast-conserving surgery]]
+# Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaft Gynäkologische Onkologie PREPARE investigators. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis. Ann Oncol. 2011 Sep;22(9):1999-2006. Epub 2011 Mar 7. [https://doi.org/10.1093/annonc/mdq713 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21382868/ PubMed]
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]]
-*[[Mitoxantrone (Novantrone)]]
-*[[Cyclophosphamide (Cytoxan)]]
-'''21-day cycle for 6 cycles'''
+==Recht et al. 1996==
-====Subsequent treatment====
-*ARCOSEIN: RT
-===References===
+===Arm 1, chemo first===
-# Ron IG, Wigler N, Borovik R, Brufman G, Rizel S, Shani A, Brenner J, Farbstein H, Dale A, Inbar MJ, Brenner HJ, Chaitchik S, Catane R. CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast  cancer: a phase III randomized multicenter study. Am J Clin Oncol. 2001 Aug;24(4):323-7. [https://insights.ovid.com/pubmed?pmid=11474254 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11474254 PubMed]
+*[[Surgery#Lumpectomy|Lumpectomy]], then [[Breast_cancer_-_historical#CAMFP|CAMFP]], then RT
-# '''HE 10/92:''' Fountzilas G, Stathopoulos G, Kouvatseas G, Polychronis A, Klouvas G, Samantas E, Zamboglou N, Kyriakou K, Adamou A, Pectasidis D, Ekonomopoulos T, Kalofonos HP, Bafaloukos D, Georgoulias V, Razis E, Koukouras D, Zombolas V, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Adjuvant cytotoxic and endocrine therapy in pre- and postmenopausal patients with breast cancer and one to nine infiltrated nodes: five-year results of the Hellenic Cooperative Oncology Group randomized HE 10/92 study. Am J Clin Oncol. 2004 Feb;27(1):57-67. [https://insights.ovid.com/pubmed?pmid=14758135 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14758135 PubMed]
+===Arm 2, RT first===
-# '''ARCOSEIN:''' Toledano A, Azria D, Garaud P, Fourquet A, Serin D, Bosset JF, Miny-Buffet J, Favre A, Le Floch O, Calais G. Phase III trial of concurrent or sequential adjuvant chemoradiotherapy after conservative surgery for early-stage breast cancer: final results of the ARCOSEIN trial. J Clin Oncol. 2007 Feb 1;25(4):405-10. Erratum in: J Clin Oncol. 2007 Jun 1;25(16):2334. [https://ascopubs.org/doi/full/10.1200/JCO.2006.07.8576 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17264336 PubMed]
+*[[Surgery#Lumpectomy|Lumpectomy]], then RT, then [[Breast_cancer_-_historical#CAMFP|CAMFP]]
+===Comparative efficacy===
-==Levamisole monotherapy {{#subobject:b051c5|Regimen=1}}==
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!style="width: 50%"|'''anti-HER2 medication'''
+!style="width: 50%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[[#top|back to top]]
+|Chemo first
-|}
+| style="background-color:#91cf60" |Seems to have superior MFS
-===Regimen {{#subobject:ec3553|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)91337-4/fulltext Rojas et al. 1976]
-|style="background-color:#1a9851"|Randomized (E-esc)
-|[[#Observation|Observation]]
-| style="background-color:#91cf60" |Seems to have superior OS
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90173-7/fulltext Brincker et al. 1980]
+|RT first
-|style="background-color:#1a9851"|Randomized (E-switch-ooc)
+| style="background-color:#fc8d59" |Seems to have inferior MFS
-|RT
-| style="background-color:#fc8d59" |Seems to have inferior RFS
 |-
 |}
-''Note: Rojas et al. 1976 included patients with inoperable breast cancer; definitive therapy was RT.''
-====Preceding treatment====
-*Rojas et al. 1976: Radiotherapy
-*Brincker et al. 1980: [[Surgery#Breast_cancer_surgery|Surgery]]
-====Immunotherapy====
-*[[Levamisole (Ergamisol)]]
 ===References===
-# Rojas AF, Feierstein JN, Mickiewicz E, Glait H, Olivari AJ. Levamisole in advanced human breast cancer. Lancet. 1976 Jan 31;1(7953):211-5. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)91337-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/55529 PubMed]
+# Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, Shulman LN, Harris JR. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356-61. [https://doi.org/10.1056/NEJM199605233342102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8614420/ PubMed]
-# Brincker H, Mouridsen HT, Andersen KW, Andersen J, Castberg T, Fischermann K, Henriksen E, Hou-Jensen C, Johansen H, Rossing N, Rorth M; Executive Committee of the Danish Breast Cancer Cooperative Group. Increased breast-cancer recurrence rate after adjuvant therapy with levamisole: a preliminary report. Lancet. 1980 Oct 18;2(8199):824-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90173-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6107500 PubMed]
-==Melphalan monotherapy {{#subobject:b062c5|Regimen=1}}==
+==SBG 9401==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
+===Arm 1 (control)===
-|[[#top|back to top]]
+*[[Surgery]], then [[Breast_cancer#FEC_2|FEC]] x 2, then HD-FEC x 1, then [[Breast_cancer_-_historical#CTCb.2C_then_auto_HSCT|CTCb with auto HSCT]]
-|}
+===Arm 2 (experimental)===
-P: '''<u>P</u>'''henylalanine mustard (Melphalan)
+*Tailored FEC x 6
-===Regimen {{#subobject:ec3663|Variant=1}}===
+===Comparative efficacy===
-{| class="wikitable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+!'''Regimen'''
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 Fisher et al. 1975 (NSABP B-05)]
-|style="background-color:#1a9851"|Phase III (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#d9ef8b" |Might have superior DFS (*)
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 Fisher et al. 1977 (NSABP B-07)]
+|Control
-| style="background-color:#1a9851" |Phase III (C)
-|[[#PF|PF]]
 | style="background-color:#fc8d59" |Seems to have inferior RFS
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91385-5/fulltext Rubens et al. 1983]
+|Experimental
-|style="background-color:#1a9851"|Phase III (E-esc)
+| style="background-color:#91cf60" |Seems to have superior RFS
-|[[#Observation|Observation]]
-| style="background-color:#d9ef8b" |Might have superior RFS
 |-
 |}
-''Note: Fisher et al. 1977 is an update for NSABP B-05 and also the primary results for NSABP B-07. Efficacy for NSABP B-05 is based on the 1986 update.''
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Melphalan (Alkeran)]]
 ===References===
-# '''NSABP B-05:''' Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. [https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1105174 PubMed]
+# Bergh J, Wiklund T, Erikstein B, Lidbrink E, Lindman H, Malmström P, Kellokumpu-Lehtinen P, Bengtsson NO, Söderlund G, Anker G, Wist E, Ottosson S, Salminen E, Ljungman P, Holte H, Nilsson J, Blomqvist C, Wilking N; Scandinavian Breast Group 9401 study. Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000 Oct 21;356(9239):1384-91. Erratum in: Lancet 2000 Dec 23-30;356(9248):2196. [https://doi.org/10.1016/s0140-6736(00)02841-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11052580/ PubMed]
-## '''Update:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2883::AID-CNCR2820390676%3E3.0.CO;2-9/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
-## '''Update:''' Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. [https://ascopubs.org/doi/full/10.1200/JCO.1986.4.6.929 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3519883 PubMed]
-# '''NSABP B-07:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
-# Rubens RD, Hayward JL, Knight RK, Bulbrook RD, Fentiman IS, Chaudary M, Howell A, Bush H, Crowther D, Sellwood RA, George WD, Howat JM. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet. 1983 Apr 16;1(8329):839-43. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(83)91385-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6132179 PubMed]
-==MF {{#subobject:e1def3|Regimen=1}}==
+==SWOG-8814==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Arm 1 (Control)===
+*[[Surgery]], then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|tamoxifen]] x 5 y
+===Arm 2, CAF-T (Experimental)===
+*[[Surgery]], then [[Breast_cancer#FAC_2|CAF]] x 6, then [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_3|tamoxifen]] x 5 y
+===Arm 3, CAFT (Experimental)===
+*[[Surgery]], then CAFT
+===Comparative efficacy===
+====Comparison 1====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Design'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|No chemotherapy
-|}
+| style="background-color:#fee08b" |Might have inferior OS
-MF: '''<u>M</u>'''ethotrexate & 5-'''<u>F</u>'''luorouracil
-===Regimen {{#subobject:c6e0a3|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 Fisher et al. 1989 (NSABP B-13)]
+|With chemotherapy
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#d9ef8b" |Might have superior OS
-|[[#Observation|Observation]]
-| style="background-color:#1a9850" |Superior DFS (*)
-|-
-|[https://academic.oup.com/jnci/article-abstract/85/10/812/1024452 Shapiro et al. 1993]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer#CMF|CMF]]
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 Fisher et al. 1996 (NSABP B-19)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer#CMF|CMF]]
-| style="background-color:#fee08b" |Might have inferior OS
 |-
 |}
-''Note: Reported efficacy for NSABP B-13 is based on the 1996 update.''
+====Comparison 2====
-====Preceding treatment====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*[[Surgery#Breast_cancer_surgery|Surgery]]
+!'''Timing'''
-====Chemotherapy====
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-===References===
-# '''NSABP B-13:''' Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644531 PubMed]
-## '''Update:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
-## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
-# Shapiro CL, Gelman RS, Hayes DF, Osteen R, Obando A, Canellos GP, Frei E 3rd, Henderson IC. Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes. J Natl Cancer Inst. 1993 May 19;85(10):812-7. [https://academic.oup.com/jnci/article-abstract/85/10/812/1024452 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8487326 PubMed]
-# '''NSABP B-19:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
-## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
-==MV {{#subobject:eb48eb|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|Concurrent (CAFT)
-|}
+| style="background-color:#fee08b" |Might have inferior DFS
-MV: '''<u>M</u>'''ethotrexate & '''<u>V</u>'''inblastine
-===Regimen {{#subobject:883648|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full Assikis et al. 2003]
+|Sequential (CAF-T)
-|style="background-color:#1a9851"|Phase III (E-switch-ooc)
+| style="background-color:#d9ef8b" |Might have superior DFS
-|[[Complex_multipart_regimens#Assikis_et_al._2003|See link]]
-| style="background-color:#ffffbf" |[[Complex_multipart_regimens#Assikis_et_al._2003|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.''
+===References===
-====Preceding treatment====
+# Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK; Breast Cancer Intergroup of North America. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-2063. Epub 2009 Dec 10. [https://doi.org/10.1016/S0140-6736(09)61523-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20004966/ PubMed]
-*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#FAC|FAC]] x 6
-====Chemotherapy====
-*[[Methotrexate (MTX)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Vinblastine (Velban)]] 1.7 mg/m<sup>2</sup>/day continuous infusion over 120 hours, started on day 1 (total dose per cycle: 8.5 mg/m<sup>2</sup>)
-====Supportive medications====
+==TRYPHAENA==
-*[[Folinic acid (Leucovorin)]] rescue
-'''21- to 28-day cycle for 4 cycles'''
+===Arm A===
+*FEC & HP x 3, then [[Breast_cancer,_HER2-positive#THP_.28Docetaxel.29|THP]] x 3, then [[surgery]]
+===Arm B===
+*[[Breast_cancer#FEC|FEC]] x 3, then [[Breast_cancer,_HER2-positive#THP_.28Docetaxel.29|THP]] x 3, then [[surgery]]
+===Arm C===
+*[[Breast_cancer,_HER2-positive#TCHP_.28Docetaxel.29|TCHP]] x 6, then [[surgery]]
+===Comparative efficacy===
+''Note: this was a cardiac safety study; efficacy findings are not reported.''
+===References===
+# Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84. Epub 2013 May 22. [https://doi.org/10.1093/annonc/mdt182 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23704196/ PubMed]
-===References===
+=Cervical cancer=
-# Assikis V, Buzdar A, Yang Y, Smith T, Theriault R, Booser D, Valero V, Walters R, Singletary E, Ames F, Hortobagyi G. A phase III trial of sequential adjuvant chemotherapy for operable breast carcinoma: final analysis with 10-year follow-up. Cancer. 2003 Jun 1;97(11):2716-23. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.11396/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12767083 PubMed]
+==NOGGO-AGO==
-==Observation==
+===Arm 1 (Control)===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Surgery]], then [[Cervical_cancer#Carboplatin_.26_Ifosfamide|adjuvant Carboplatin & Ifosfamide]] x 4, then [[Cervical_cancer#Radiation_therapy_2|EBRT]]
-|-
+===Arm 2 (Experimental)===
-|[[#top|back to top]]
+*[[Surgery]], then adjuvant Carboplatin, Ifosfamide, Erythropoietin alfa, then EBRT & Erythropoietin alfa
-|}
+===Comparative efficacy===
-===Regimen===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="width: 100%; text-align:center;"
+!'''Regimen'''
-!style="width: 25%"|Study
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM197602192940801 Bonadonna et al. 1976]
-|style="background-color:#1a9851"|Phase III (C)
-|[[Breast_cancer#CMF|CMF]]
-|style="background-color:#d73027"|Inferior RFS
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90057-4/fulltext Lacour et al. 1980]
-|style="background-color:#1a9851"|Phase III (C)
-|Polya.Polyu
-| style="background-color:#fee08b" |Might have inferior OS
-|-
-|rowspan=3|[https://link.springer.com/article/10.1007/BF01806239 Brinker et al. 1983 (DBCG 77B)]
-|rowspan=3 style="background-color:#1a9851" |Phase III (C)
-|1. [[Breast_cancer#CMF|CMF]]
-| style="background-color:#fc8d59" |Seems to have inferior OS (*)
-|-
-|2. [[#Cyclophosphamide_monotherapy|Cyclophosphamide]]
-| style="background-color:#fc8d59" |Seems to have inferior OS (*)
-|-
-|3. [[#Levamisole_monotherapy|Levamisole]]
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
-|rowspan = 2 style="background-color:#1a9851" |Phase III (C)
-|1. [[#CMFPT|CMFPT]]
-| style="background-color:#d73027" |Inferior DFS
-|-
-|2. [[#PT|PT]]
-| style="background-color:#d73027" |Inferior DFS
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS IV)]
-|style="background-color:#1a9851" |Phase III (C)
-|[[#PT|PT]]
-| style="background-color:#fc8d59" |Seems to have inferior DFS
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 Fisher et al. 1989 (NSABP B-13)]
+|No EPO
-| style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#fee08b"|Might have inferior RFS
-|Sequential MF
-| style="background-color:#d73027" |Inferior DFS (*)
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 Mansour et al. 1989 (INT-0011)]
+|With EPO
-| style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#d9ef8b"|Might have superior RFS
-|[[#CMFP|CMFP]]
-|style="background-color:#d73027"|Inferior DFS
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2001.19.19.3929 Paradiso et al. 2001]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer#FEC_2|FEC]]
-| style="background-color:#fc8d59" |Seems to have inferior DFS
-|-
-|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
-|style="background-color:#1a9851"|Phase III (C)
-|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel q3wk]]
-|style="background-color:#d73027"|Inferior OS
-|-
-|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
-|style="background-color:#1a9851"|Phase III (C)
-|[[#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel q3wk]]
-|style="background-color:#d73027"|Inferior DFS
 |-
 |}
-''No further systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Reported efficacy for DBCG 77B is based on the 2010 update. Reported efficacy for NSABP B-13 is based on the 1996 update.''
-====Preceding treatment====
-*Bonadonna et al. 1976: [[Surgery#Mastectomy|Mastectomy]]
-*ECOG E1180: [[Surgery#Modified_radical_mastectomy|Modified radical mastectomy]] or [[Surgery#Mastectomy|total mastectomy]] with [[Surgery#Axillary_lymph_node_dissection|low axillary-node dissection]]
-*INT 0148/CALGB 9344: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
-*NSABP B-28: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
 ===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. [https://www.nejm.org/doi/full/10.1056/NEJM197602192940801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1246307 PubMed]
+# Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Würschmidt F, Petry KU, Kimmig R, Elling D, Thomssen C, von Minckwitz G, Möbus V, Hinke A, Kümmel S, Budach V, Lichtenegger W, Schmid P. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011 Oct 1;29(28):3791-7. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2010.30.4899 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21860000/ PubMed]
-## '''Update:''' Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2904::AID-CNCR2820390677%3E3.0.CO;2-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/326384 PubMed]
-## '''Update:''' Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. [https://www.ncbi.nlm.nih.gov/pubmed/3839424 PubMed]
-## '''Update:''' Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. [https://www.nejm.org/doi/ref/10.1056/NEJM199504063321401 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7877646 PubMed]
-# Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J. Adjuvant treatment with polyadenylic-polyuridylic acid (Polya-Polyu) in operable breast cancer. Lancet. 1980 Jul 26;2(8187):161-4. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(80)90057-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6105336 PubMed]
-# '''DBCG 77B:''' Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. [https://link.springer.com/article/10.1007/BF01806239 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6347278 PubMed]
-## '''Update:''' Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.24969/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20186830 PubMed]
-# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
-# '''NSABP B-13:''' Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644531 PubMed]
-## '''Update:''' Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.1982 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683228 PubMed]
-## '''Pooled update:''' Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. [https://ascopubs.org/doi/full/10.1200/JCO.2006.06.9054 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16921044 PubMed]
-# '''INT-0011:''' Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200803 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2915651 PubMed]
-# '''LCBS V:''' Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. [https://www.nejm.org/doi/full/10.1056/NEJM198902233200804 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2644533 PubMed]
-# Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.19.3929 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11579113 PubMed]
-# '''INT 0148/CALGB 9344:''' Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. [http://jco.ascopubs.org/content/21/6/976.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12637460 PubMed]
-<!-- Presented in abstract form at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003; interim results were presented at the 2000 NIH Consensus Development Conference, Bethesda, MD, November 1-3, 2000. -->
-# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [http://jco.ascopubs.org/content/23/16/3686.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15897552 PubMed]
-==Oophorectomy==
+=[[Colorectal cancer]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==CAIRO==
-|-
-|[[#top|back to top]]
-|}
-===Regimen===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 Ahmann et al. 1977]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#CFP_.26_Oophorectomy|CFP & Oophorectomy]]
-| style="background-color:#fc8d59" |Seems to have inferior PFS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Hormonotherapy====
-*[[Endocrine_ablation_surgery#Bilateral_oophorectomy|Bilateral oophorectomy]]
-===References===
-# Ahmann DL, O'Connell MJ, Hahn RG, Bisel HF, Lee RA, Edmonson JH. An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy. N Engl J Med. 1977 Aug 18;297(7):356-60. [https://www.nejm.org/doi/full/10.1056/NEJM197708182970704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/876327 PubMed]
-==Paclitaxel monotherapy, q3wk {{#subobject:1cb87f|Regimen=1}}==
+===Arm 1, sequential single agent (Control)===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Colon_cancer#Capecitabine_monotherapy_2|First-line capecitabine]], then [[Colon_cancer#Irinotecan_monotherapy_2|second-line irinotecan]], then [[Colon_cancer#CapeOx_4|third-line CapeOx]]
-|-
+===Arm 2, sequential combinations (Experimental)===
-|[[#top|back to top]]
+*[[Colon_cancer#CAPIRI|First-line CAPIRI]], then [[Colon_cancer#CapeOx_3|second-line CapeOx]]
-|}
+===Comparative efficacy===
-T: '''<u>T</u>'''axol (Paclitaxel)
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<br>P: '''<u>P</u>'''aclitaxel
+!'''Approach'''
-<br>pT: '''<u>p</u>'''acli'''<u>T</u>'''axel
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-===Variant #1, 175 mg/m<sup>2</sup> q3wk {{#subobject:c084f5|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[http://jco.ascopubs.org/content/21/6/976.long Henderson et al. 2003 (INT 0148/CALGB 9344)]
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
-|[[#Observation|Observation]]
-| style="background-color:#1a9850" |Superior OS
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa052122 Romond et al. 2005 (NSABP B-31)]
+|Sequential single agent
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer,_HER2-positive#TH_.28Taxol.29_2|TH]]
-| style="background-color:#d73027" |Inferior OS
-|-
-| rowspan="3" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ Sparano et al. 2008 (ECOG E1199)]
-| rowspan="3" style="background-color:#1a9851" |Phase III (C)
-|1. [[Breast_cancer#Paclitaxel_monotherapy.2C_weekly_2|Weekly Paclitaxel]]
-| style="background-color:#d73027" |Inferior OS
-|-
-|2. [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel q3wk]]
-| style="background-color:#fc8d59" |Seems to have inferior DFS
-|-
-|3. [[Breast_cancer#Docetaxel_monotherapy_2|Docetaxel weekly]]
 | style="background-color:#ffffbf" |Seems not superior
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext Del Mastro et al. 2015 (GIM2)]
+|Sequential combinations
-|style="background-color:#1a9851" |Phase III (C)
-|[[Complex_multipart_regimens#GIM2|See link]]
-|[[Complex_multipart_regimens#GIM2|See link]]
-|-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext Earl et al. 2017 (tAnGo)]
-| style="background-color:#1a9851" |Phase III (C)
-|TG
 | style="background-color:#ffffbf" |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: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4 versus high-dose AC x 4 versus very-high-dose AC x 4
-*NSABP B-31, and ECOG E1199: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
-*GIM2: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#EC_2|EC]] x 4 versus [[Breast_cancer#FEC_2|FEC]] x 4
-*tAnGo: [[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#EC_2|EC]] x 4
-====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
-'''21-day cycle for 4 cycles'''
-===Variant #2, 225 mg/m<sup>2</sup> q3wk {{#subobject:b7a984|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[http://jco.ascopubs.org/content/23/16/3686.long Mamounas et al. 2005 (NSABP B-28)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#Observation|Observation]]
-| style="background-color:#1a9850" |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====
-*[[Surgery#Breast_cancer_surgery|Surgery]], then [[Breast_cancer#AC_2|AC]] x 4
-====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV over 3 hours once on day 1
-'''21-day cycle for 4 cycles'''
 ===References===
-# '''INT 0148/CALGB 9344:''' Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, Norton L. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83. [http://jco.ascopubs.org/content/21/6/976.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12637460 PubMed]
+# Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, de Jong RS, Rodenburg CJ, Vreugdenhil G, Loosveld OJ, van Bochove A, Sinnige HA, Creemers GM, Tesselaar ME, Slee PHTJ, Werter MJ, Mol L, Dalesio O, Punt CJ. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007 Jul 14;370(9582):135-142. [https://doi.org/10.1016/s0140-673607610861 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17630036/ PubMed]
-<!-- Presented in abstract form at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003; interim results were presented at the 2000 NIH Consensus Development Conference, Bethesda, MD, November 1-3, 2000. -->
-# '''NSABP B-28:''' Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. [http://jco.ascopubs.org/content/23/16/3686.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15897552 PubMed]
-<!-- no pre-pub disclosed -->
-<!-- no pre-pub disclosed -->
-# '''NSABP B-31/NCCTG N9831:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa052122 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16236738 PubMed]
-## '''Update:''' Perez EA, Romond EH, Suman VJ, Jeong JH, Davidson NE, Geyer CE Jr, Martino S, Mamounas EP, Kaufman PA, Wolmark N. Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol. 2011 Sep 1;29(25):3366-73. Epub 2011 Jul 18. [https://ascopubs.org/doi/full/10.1200/JCO.2011.35.0868 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164242/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21768458 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. [https://ascopubs.org/doi/full/10.1200/JCO.2011.36.7045 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236650/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22042958 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. [https://ascopubs.org/doi/full/10.1200/JCO.2014.55.5730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226805/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25332249 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. [https://ascopubs.org/doi/full/10.1200/JCO.2017.74.1165 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721228/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29072977 PubMed]
-<!-- Presented in part at the San Antonio Breast Cancer Symposium, San Antonio, Texas, December 8–11, 2007, and the American Society of Clinical Oncology meeting, Chicago, June 1–4, 2005. -->
-# '''ECOG E1199:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa0707056 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743943/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18420499 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. [http://jco.ascopubs.org/content/33/21/2353.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500829/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26077235 PubMed]
-# '''GIM2:''' 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62048-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25740286 PubMed]
-# '''tAnGo:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30319-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28479233 PubMed]
-==PAF {{#subobject:5750af|Regimen=1}}==
+==FFCD 2000-05==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-PAF: '''<u>P</u>'''henylalanine mustard (Melphalan), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:763980|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 Fisher et al. 1989 (NSABP B-11)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#PF|PF]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|}
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Melphalan (Alkeran)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Fluorouracil (5-FU)]]
-===References===
-# '''NSABP B-11:''' Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. [https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2651576 PubMed]
-==PF {{#subobject:3a5d5f|Regimen=1}}==
+===Arm 1, sequential (Control)===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Colon_cancer#Fluorouracil_.26_Folinic_acid_2|First-line sLV5FU2]], then [[Colon_cancer#mFOLFOX6_4|second-line mFOLFOX6]], then [[Colon_cancer#FOLFIRI_4|third-line FOLFIRI]]
-|-
+===Arm 2, combination (Experimental)===
-|[[#top|back to top]]
+*[[Colon_cancer#mFOLFOX6_3|First-line mFOLFOX6]], then [[Colon_cancer#FOLFIRI_3|second-line FOLFIRI]]
-|}
+===Comparative efficacy===
-PF: '''<u>P</u>'''henylalanine mustard (Melphalan) & '''<u>F</u>'''luorouracil
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===Regimen {{#subobject:06f47d|Variant=1}}===
+!'''Approach'''
-{| class="wikitable" style="width: 100%; text-align:center;"
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|Study
+![[Levels_of_Evidence#Toxicity|Toxicity]]
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 Fisher et al. 1977 (NSABP B-07)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#Melphalan_monotherapy|P]]
-| style="background-color:#91cf60" |Seems to have superior RFS
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19800815)46:4%2B%3C1009::AID-CNCR2820461326%3E3.0.CO;2-H Fisher et al. 1980 (NSABP B-08)]
+|Sequential
-| style="background-color:#1a9851" |Phase III (C)
-|PFM
 | style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#1a9850" |Less toxic
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 Fisher et al. 1981 (NSABP B-09)]
+|Combination
-| style="background-color:#1a9851" |Phase III (C)
-|[[#PFT|PFT]]
-| style="background-color:#d73027" |Inferior RFS
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 Fisher et al. 1989 (NSABP B-11)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#PAF|PAF]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|-
-|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2819900715%2966%3A2%3C220%3A%3AAID-CNCR2820660205%3E3.0.CO%3B2-6 Fisher et al. 1990 (NSABP B-10)]
-| style="background-color:#1a9851" |Phase III (C)
-|PFCp
 | style="background-color:#ffffbf" |Seems not superior
+| style="background-color:#d73027" |More toxic
 |-
 |}
-''Note: Fisher et al. 1980 is more of a meta-analysis than a primary publication, but is to our knowledge the first manuscript to report the findings from NSABP B-08, which was a negative trial.''
-====Preceding treatment====
-*[[Surgery#Breast_cancer_surgery|Surgery]]
-====Chemotherapy====
-*[[Melphalan (Alkeran)]]
-*[[Fluorouracil (5-FU)]]
 ===References===
-# '''NSABP B-07:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%28197706%2939%3A6%3C2883%3A%3AAID-CNCR2820390676%3E3.0.CO%3B2-9 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
+# Ducreux M, Malka D, Mendiboure J, Etienne PL, Texereau P, Auby D, Rougier P, Gasmi M, Castaing M, Abbas M, Michel P, Gargot D, Azzedine A, Lombard-Bohas C, Geoffroy P, Denis B, Pignon JP, Bedenne L, Bouché O; Fédération Francophone de Cancérologie Digestive (FFCD) 2000–05 Collaborative Group. Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial. Lancet Oncol. 2011 Oct;12(11):1032-44. Epub 2011 Sep 6. [https://doi.org/10.1016/s1470-2045(11)70199-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21903473/ PubMed]
-# '''NSABP B-08:''' Fisher B, Redmond C, Fisher ER. The contribution of recent NSABP clinical trials of primary breast cancer therapy to an understanding of tumor biology--an overview of findings. Cancer. 1980 Aug 15;46(4 Suppl):1009-25. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19800815)46:4%2B%3C1009::AID-CNCR2820461326%3E3.0.CO;2-H link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6994873 PubMed]
-# '''NSABP B-09:''' Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. [https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7015139 PubMed]
-## '''Update:''' Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. [https://ascopubs.org/doi/abs/10.1200/JCO.1986.4.4.459 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2856857 PubMed]
-## '''Update:''' Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. [http://annals.org/aim/article-abstract/701830/prolonging-tamoxifen-therapy-primary-breast-cancer-findings-from-national-surgical link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3551710 PubMed]
-# '''NSABP B-11:''' Fisher B, Redmond C, Wickerham DL, Bowman D, Schipper H, Wolmark N, Sass R, Fisher ER, Jochimsen P, Legault-Poisson S, Dimitrov N, Wolter J, Bornstein R, Elias EG, LiCalzi N, Paterson AHG, Sutherland CM. Doxorubicin-containing regimens for the treatment of stage II breast cancer: the National Surgical Adjuvant Breast and Bowel Project experience. J Clin Oncol. 1989 May;7(5):572-82. [https://ascopubs.org/doi/abs/10.1200/JCO.1989.7.5.572 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2651576 PubMed]
-# '''NSABP B-10:''' Fisher B, Brown A, Wolmark N, Fisher ER, Redmond C, Wickerham DL, Margolese R, Dimitrov N, Pilch Y, Glass A, Sutherland C, Foster R. Evaluation of the worth of corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer: eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10. Cancer. 1990 Jul 15;66(2):220-7. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2819900715%2966%3A2%3C220%3A%3AAID-CNCR2820660205%3E3.0.CO%3B2-6 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2196108 PubMed]
-==PFT {{#subobject:1cb87f|Regimen=1}}==
+=[[Diffuse large B-cell lymphoma]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==SWOG S8736==
+===Arm 1 - Control===
+*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8
+===Arm 2 - Experimental===
+*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, then [[Diffuse_large_B-cell_lymphoma#Radiation_therapy|RT]] x 40 to 5500 cGy
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|CHOP x 8
-|}
+|style="background-color:#fc8d59"|Seems to have inferior OS
-PFT: '''<u>P</u>'''henylalanine mustard (Melphalan), 5-'''<u>F</u>'''luorouracil, '''<u>T</u>'''amoxifen
-===Regimen {{#subobject:c084f5|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 Fisher et al. 1981 (NSABP B-09)]
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
-|[[#PF|PF]]
-| style="background-color:#1a9850" |Superior RFS
-|-
-|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 Fisher et al. 1990 (NSABP B-16)]
-|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[#ACT|ACT]]
-| style="background-color:#d3d3d3" |Not reported
 |-
-|2. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy|Tamoxifen]]
+|CHOP x 3, then RT
-| style="background-color:#91cf60" |Seems to have superior DDFS
+|style="background-color:#91cf60"|Seems to have superior OS
 |-
 |}
-====Preceding treatment====
+===References===
-*[[Surgery#Breast_cancer_surgery|Surgery]]
+# Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. [https://doi.org/10.1056/NEJM199807023390104 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9647875/ PubMed]
-====Chemotherapy====
-*[[Melphalan (Alkeran)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Tamoxifen (Nolvadex)]]
-===References===
+=[[Endometrial cancer]]=
-# '''NSABP B-09:''' Fisher B, Redmond C, Brown A, Wolmark N, Wittliff J, Fisher ER, Plotkin D, Bowman D, Sachs S, Wolter J, Frelick R, Desser R, LiCalzi N, Geggie P, Campbell T, Elias EG, Prager D, Koontz P, Volk H, Dimitrov N, Gardner B, Lerner H, Shibata H. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981 Jul 2;305(1):1-6. [https://www.nejm.org/doi/full/10.1056/NEJM198107023050101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7015139 PubMed]
+==PORTEC-3==
-## '''Update:''' Fisher B, Redmond C, Brown A, Fisher ER, Wolmark N, Bowman D, Plotkin D, Wolter J, Bornstein R, Legault-Poisson S, Saffer EA. Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project Trial. J Clin Oncol. 1986 Apr;4(4):459-71. [https://ascopubs.org/doi/abs/10.1200/JCO.1986.4.4.459 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2856857 PubMed]
-## '''Update:''' Fisher B, Brown A, Wolmark N, Redmond C, Wickerham DL, Wittliff J, Dimitrov N, Legault-Poisson S, Schipper H, Prager D. Prolonging tamoxifen therapy for primary breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project clinical trial. Ann Intern Med. 1987 May;106(5):649-54. [http://annals.org/aim/article-abstract/701830/prolonging-tamoxifen-therapy-primary-breast-cancer-findings-from-national-surgical link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3551710 PubMed]
-# '''NSABP B-16:''' Fisher B, Redmond C, Legault-Poisson S, Dimitrov NV, Brown AM, Wickerham DL, Wolmark N, Margolese RG, Bowman D, Glass AG, Kardinal CG, Robidoux A, Jochimsen P, Cronin W, Deutsch M, Fisher ER, Myers DB, Hoehn JL. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990 Jun;8(6):1005-18. [https://ascopubs.org/doi/abs/10.1200/JCO.1990.8.6.1005 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2189950 PubMed]
-## '''Pooled update:''' Taghian A, Jeong JH, Mamounas E, Anderson S, Bryant J, Deutsch M, Wolmark N. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004 Nov 1;22(21):4247-54. Epub 2004 Sep 27. [https://ascopubs.org/doi/full/10.1200/JCO.2004.01.042 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15452182 PubMed]
-==Placebo==
+===Arm 1 - Control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Surgery#Endometrial_cancer_surgery|Surgery]], then [[Endometrial_cancer#Radiation_therapy|RT]]
+===Arm 2 - Experimental===
+*[[Surgery#Endometrial_cancer_surgery|Surgery]], then [[Endometrial_cancer#Cisplatin_.26_RT|Cisplatin & RT]], then [[Endometrial_cancer#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]]
+===Comparative efficacy===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 50%"|Modality
+!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Radiotherapy
-|}
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
-===Regimen===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 Fisher et al. 1975 (NSABP B-05)]
+|Chemoradiotherapy
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
-|[[#Melphalan_monotherapy|Melphalan]]
-|style="background-color:#fee08b" |Might have inferior DFS (*)
 |-
 |}
-''No active antineoplastic treatment after mastectomy. Used as a comparator arm, historically. Reported efficacy for NSABP B-05 is based on the 1986 update.''
+''<sup>1</sup>Reported efficacy is based on the 2019 update.''
-====Preceding treatment====
-*[[Surgery#Mastectomy|Mastectomy]]
 ===References===
-# '''NSABP B-05:''' Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. [https://www.nejm.org/doi/full/10.1056/NEJM197501162920301 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1105174 PubMed]
+# de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. Epub 2018 Feb 12. [https://doi.org/10.1016/S1470-2045(18)30079-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840256/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29449189/ PubMed]
-## '''Update:''' Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197706)39:6%3C2883::AID-CNCR2820390676%3E3.0.CO;2-9/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/194679 PubMed]
+## '''Update:''' de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. 2019 Sep;20(9):1273-1285. Epub 2019 Jul 22. Erratum in: Lancet Oncol. 2019 Sep;20(9):e468. [https://doi.org/10.1016/S1470-2045(19)30395-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/31345626/ PubMed]
-## '''Update:''' Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. [https://ascopubs.org/doi/full/10.1200/JCO.1986.4.6.929 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3519883 PubMed]
+=[[Follicular lymphoma]]=
+==GALLIUM==
-==PT {{#subobject:c08464|Regimen=1}}==
+===Arm 1 - Control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Follicular_lymphoma#Bendamustine_.26_Rituximab_.28BR.29|BR]] x 6 or [[Follicular_lymphoma#R-CHOP|R-CHOP]] x 8 or [[Follicular_lymphoma#R-CVP|R-CVP]] x 8, then [[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance x 2 y
-|-
+===Arm 2 - Experimental===
-|[[#top|back to top]]
+*[[Follicular_lymphoma#Bendamustine_.26_Obinutuzumab|Bendamustine & Obinutuzumab]] x 6 or [[Follicular_lymphoma#G-CHOP|G-CHOP]] x 8 or [[Follicular_lymphoma#G-CVP|G-CVP]] x 8, then [[Follicular_lymphoma#Obinutuzumab_monotherapy|Obinutuzumab]] maintenance x 2y
-|}
+===Comparative efficacy===
-PT: '''<u>P</u>'''rednisone & '''<u>T</u>'''amoxifen
+{| class="wikitable" style="width: 60%; text-align:center;"
-===Regimen {{#subobject:2fc709|Variant=1}}===
+!style="width: 33%"|mAb
-{| class="wikitable" style="width: 100%; text-align:center;"
+!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|Study
+!style="width: 33%"|[[Levels_of_Evidence#Toxicity|Toxicity]]
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan = 2|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS III)]
+|Rituximab-chemotherapy
-|rowspan = 2 style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#d73027" |Inferior PFS
-|1. [[#CMFPT|CMFPT]]
+| style="background-color:#1a9850" |Superior toxicity
-| style="background-color:#fc8d59" |Seems to have inferior DFS
 |-
-|2. [[#Observation|Observation]]
+|Obinutuzumab-chemotherapy
-| style="background-color:#1a9850" |Superior DFS
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS36: 80% vs 73%<br>(HR 0.66, 95% CI 0.51-0.85)
-|-
+| style="background-color:#d73027" |Inferior toxicity
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext Goldhirsch et al. 1984 (LBCS IV)]
-|style="background-color:#1a9851" |Phase III (E-esc)
-|[[#Observation|Observation]]
-| style="background-color:#91cf60" |Seems to have superior DFS
 |-
 |}
-====Preceding treatment====
-*[[Surgery#Mastectomy|Mastectomy]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
-*[[Tamoxifen (Nolvadex)]]
 ===References===
-# '''LBCS III/IV:''' Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673684924450/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6144974 PubMed]
+# Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med. 2017 Oct 5;377(14):1331-1344. [https://doi.org/10.1056/NEJMoa1614598 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1614598/suppl_file/nejmoa1614598_appendix.pdf link to appendix] [https://pubmed.ncbi.nlm.nih.gov/28976863/ PubMed]
-==TMF {{#subobject:c08464|Regimen=1}}==
+=Gastroesophageal cancer=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==POET==
+===Arm 1===
+*[[Esophageal_cancer#CLF|PLF]] x 15 wk, then [[surgery]]
+===Arm 2===
+*[[Esophageal_cancer#CLF|PLF]] x 12 wk, then [[Esophageal_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]], then [[surgery]]
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Neoadjuvant chemotherapy only
-|}
+|style="background-color:#fee08b"|Might have inferior OS
-TMF: '''<u>T</u>'''hiotepa, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:2fc709|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://academic.oup.com/annonc/article-abstract/5/7/591/206435 Semiglazov et al. 1994]
+|Neoadjuvant chemotherapy and chemoradiotherapy
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+|style="background-color:#d9ef8b"|Might have superior OS
 |-
 |}
-====Preceding treatment====
-*[[Surgery#Mastectomy|Mastectomy]]
-====Chemotherapy====
-*[[Thiotepa (Thioplex)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
 ===References===
-# Semiglazov VF, Topuzov EE, Bavli JL, Moiseyenko VM, Ivanova OA, Seleznev IK, Orlov AA, Barash NY, Golubeva OM, Chepic OF. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994 Sep;5(7):591-5. [https://academic.oup.com/annonc/article-abstract/5/7/591/206435 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7993833 PubMed]
+# Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [https://doi.org/10.1200/JCO.2008.17.0506 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19139439/ PubMed]
-=Metastatic disease, all lines of therapy=
-==Aminoglutethimide monotherapy {{#subobject:821a2c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:f62b32|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)92759-9/fulltext Smith et al. 1978]
-| style="background-color:#91cf61" |Non-randomized
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198109033051003 Santen et al. 1981]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|Bilateral adrenalectomy
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)90596-8/fulltext Stuart-Harris et al. 1984]
-| style="background-color:#91cf61" |Phase II
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 Canney et al. 1988]
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
-|[[#Medroxyprogesterone_monotherapy|MPA]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
-|-
-|[https://link.springer.com/article/10.1007/BF01810736 Lundgren et al. 1989]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[#Megestrol_monotherapy|Megestrol]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://link.springer.com/article/10.1007/BF01961246 Garcia-Giralt et al. 1992]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[#Medroxyprogesterone_monotherapy|MPA]]
-| style="background-color:#91cf60" |Seems to have superior TTP
-|-
-|[https://www.ncbi.nlm.nih.gov/pubmed/8135469 Robustelli della Cuna et al. 1993]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]; higher-dose
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J Gale et al. 1994]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]<br> 2. Bilateral adrenalectomy
-| style="background-color:#ffffbf" |Did not meet primary endpoints of DOR/TTF/OS
-|-
-|}
-====Hormonotherapy====
-*[[Aminoglutethimide (Cytadren)]]
-====Supportive medications====
+==PRODIGE5/ACCORD17==
-*[[Hydrocortisone (Cortef)]]
-===References===
-# Smith IE, Fitzharris BM, McKinna JA, Fahmy DR, Nash AG, Neville AM, Gazet JC, Ford HT, Powles TJ. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646-9. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(78)92759-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/80576 PubMed]
-# Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, Lipton A, Harvey HA, White DS, Smart E, Cox C, Wells SA. A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. N Engl J Med. 1981 Sep 3;305(10):545-51. [https://www.nejm.org/doi/full/10.1056/NEJM198109033051003 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7019703 PubMed]
-# Stuart-Harris R, Dowsett M, Bozek T, McKinna JA, Gazet JC, Jeffcoate SL, Kurkure A, Carr L, Smith IE. Low-dose aminoglutethimide in treatment of advanced breast cancer. Lancet. 1984 Sep 15;2(8403):604-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)90596-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6147642 PubMed]
-# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. [https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2970555 PubMed]
-# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. [https://link.springer.com/article/10.1007/BF01810736 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2690972 PubMed]
-# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. [https://link.springer.com/article/10.1007/BF01961246 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8443401 PubMed]
-# Robustelli della Cuna G, Pannuti F, Martoni A, Camaggi CM, Strocchi E, Da Prada GA, Tanneberger S; Italian Cooperative Group. Aminoglutethimide in advanced breast cancer: prospective, randomized comparison of two dose levels. Anticancer Res. 1993 Nov-Dec;13(6B):2367-71. [https://www.ncbi.nlm.nih.gov/pubmed/8135469 PubMed]
-# Gale KE, Andersen JW, Tormey DC, Mansour EG, Davis TE, Horton J, Wolter JM, Smith TJ, Cummings FJ. Hormonal treatment for metastatic breast cancer: an Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer. 1994 Jan 15;73(2):354-61. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19940115)73:2%3C354::AID-CNCR2820730220%3E3.0.CO;2-J link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8293400 PubMed]
-==CAMF {{#subobject:4b99b8|Regimen=1}}==
+===Arm 1 - Control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Esophageal_cancer#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT_2|Definitive CF & RT]], then [[Esophageal_cancer#Cisplatin_.26_Fluorouracil_.28CF.29_2|CF]] x 2
+===Arm 2 - Experimental===
+*[[Esophageal_cancer#FOLFOX4_.26_RT|Definitive FOLFOX4 & RT]], then [[Esophageal_cancer#FOLFOX4|FOLFOX4]] x 3
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|CF-based
-|}
+| style="background-color:#ffffbf" |Seems not superior
-CAMF: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
-<br>AFCM: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate
-===Regimen {{#subobject:7c9b85|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q Tranum et al. 1978]
-| style="background-color:#1a9851" |Randomized (E-esc)
-|1. AF<br> 2. [[Breast_cancer#FAC_3|FAC]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D Bezwoda et al. 1979]
-|style="background-color:#1a9851" |Randomized (E-switch-ic)
-|[[#CMFV|CMFV]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.1.28 Lippman et al. 1984]
+|FOLFOX4-based
-| style="background-color:#1a9851" |Randomized (C)
-|CAMFTP
 | style="background-color:#ffffbf" |Seems not superior
 |-
 |}
-====Chemotherapy====
+===References===
-*[[Cyclophosphamide (Cytoxan)]]
+# Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [https://doi.org/10.1016/S1470-2045(14)70028-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24556041/ PubMed]
-*[[Doxorubicin (Adriamycin)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-===References===
+=[[Glioblastoma]]=
-# Tranum B, Hoogstraten B, Kennedy A, Vaughn CB, Samal B, Thigpen T, Rivkin S, Smith F, Palmer RL, Costanzi J, Tucker WG, Wilson H, Maloney TR. Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study. Cancer. 1978 Jun;41(6):2078-83. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197806)41:6%3C2078::AID-CNCR2820410602%3E3.0.CO;2-Q link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/657081 PubMed]
+==AVAglio==
-# Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/383254 PubMed]
-# Lippman ME, Cassidy J, Wesley M, Young RC. A randomized attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization. J Clin Oncol. 1984 Jan;2(1):28-36. [https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.1.28 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6321686 PubMed]
-==CAF & MPA {{#subobject:6c7ff9|Regimen=1}}==
+===Arm 1, control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|temozolomide]] maintenance
+===Arm 2, experimental===
+*[[Surgery]], then adjuvant temozolomide, bevacizumab, RT, then temozolomide & bevacizumab maintenance, then bevacizumab maintenance
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Temozolomide alone
-|}
+|style="background-color:#d73027"|Inferior PFS
-CAF & MPA: '''<u>C</u>'''yclophosphamide,  '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>M</u>'''edroxy'''<u>P</u>'''rogesterone '''<u>A</u>'''cetate
-===Regimen {{#subobject:b2ce67|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ejcancer.com/article/0959-8049(94)90123-6/pdf Tominaga et al. 1994]
+|Bevacizumab-containing arm
-| style="background-color:#1a9851" |Phase III (E-esc)
+|style="background-color:#1a9850"|Superior PFS
-|[[Breast_cancer#FAC_3|CAF]]
-| style="background-color:#91cf60" |Seems to have superior ORR
 |-
 |}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Medroxyprogesterone (MPA)]]
 ===References===
-# Tominaga T, Abe O, Ohshima A, Hayasaka H, Uchino J, Abe R, Enomoto K, Izuo M, Watanabe H, Takatani O, Yoshida M, Sakai K, Koyama H, Hattori T, Senoo T, Monden Y, Nomura Y. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer. 1994;30A(7):959-64. [https://www.ejcancer.com/article/0959-8049(94)90123-6/pdf link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7946592 PubMed]
+# Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):709-22. [https://doi.org/10.1056/NEJMoa1308345 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24552318/ PubMed]
-==CAFVP {{#subobject:918bda|Regimen=1}}==
+==EORTC 22981/26981; NCIC-CTG CE.3==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Arm 1, control===
+*[[Surgery]], then [[Glioblastoma#Radiation_therapy|adjuvant radiotherapy]]
+===Arm 2, experimental===
+*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant Temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|Temozolomide]] maintenance
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Radiotherapy alone
-|}
+|style="background-color:#d73027"|Inferior OS
-CAFVP: '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
-===Regimen {{#subobject:e01caf|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 Muss et al. 1978]
-|style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[#CMFVP_2|CMFVP]]
-| style="background-color:#d9ef8b" |Might have superior OS
-|-
-|rowspan=2|[https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.10.1523 Aisner et al. 1987]
-|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[Breast_cancer#FAC_3|CAF]]
-| style="background-color:#d3d3d3" |Not reported
 |-
-|2. [[Breast_cancer#CMF_2|CMF]]
+|Temozolomide-containing arm
-| style="background-color:#1a9850" |Superior ORR
+|style="background-color:#1a9850"|Superior OS
 |-
 |}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Fluorouracil (5-FU)]]
-*[[Vincristine (Oncovin)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
 ===References===
-# Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/363253 PubMed]
+# Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; [[Study_Groups#EORTC|EORTC]] Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. [https://doi.org/10.1056/NEJMoa043330 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15758009/ PubMed]
-# Aisner J, Weinberg V, Perloff M, Weiss R, Perry M, Korzun A, Ginsberg S, Holland JF; Cancer and Leukemia Group B. Chemotherapy versus chemoimmunotherapy (CAF v CAFVP v CMF each +/- MER) for metastatic carcinoma of the breast: a CALGB study. J Clin Oncol. 1987 Oct;5(10):1523-33. [https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.10.1523 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3655855 PubMed]
-==CFP {{#subobject:ba429d|Regimen=1}}==
+==RTOG 0825==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
+===Arm 1, control===
-|[[#top|back to top]]
+*[[Surgery]], then [[Glioblastoma#Temozolomide_.26_RT|adjuvant Temozolomide & RT]], then [[Glioblastoma#Temozolomide_monotherapy_2|Temozolomide]] maintenance
-|}
+===Arm 2, experimental===
-CFP: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
+*[[Surgery]], then adjuvant Temozolomide, Bevacizumab, RT, then Temozolomide & Bevacizumab maintenance
-===Regimen {{#subobject:26519a|Variant=1}}===
+===Comparative efficacy===
-{| class="wikitable" style="width: 100%; text-align:center;"
+''Note: although the control regimen had inferior PFS, the effect size did not reach the prespecified improvement target.''
-!style="width: 25%"|Study
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!'''Regimen'''
-!style="width: 25%"|Comparator
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://ascopubs.org/doi/10.1200/JCO.1984.2.11.1260 Creagan et al. 1984]
-| style="background-color:#1a9851" |Phase III (C)
-|CAP, then CFP
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
+|Temozolomide alone
-| style="background-color:#1a9851" |Phase III (E-esc)
+|style="background-color:#d73027"|Inferior PFS
-|1. [[Breast_cancer#AC_3|CA]]<br> 2. [[#CMFVP_2|CMFVP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F Marschke et al. 1989]
+|Bevacizumab-containing arm
-| style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#1a9850"|Superior PFS (co-primary endpoint)
-|[[#CMFP_2|CMFP]]
-| style="background-color:#fee08b" |Might have inferior ORR
 |-
 |}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
 ===References===
-# Creagan ET, Green SJ, Ahmann DL, Ingle JN, Edmonson JH, Marschke RF Jr. A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer. J Clin Oncol. 1984 Nov;2(11):1260-5. [https://ascopubs.org/doi/10.1200/JCO.1984.2.11.1260 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6387059 PubMed]
+# Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran WJ Jr, Mehta MP. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014 Feb 20;370(8):699-708. [https://doi.org/10.1056/NEJMoa1308573 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201043/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24552317/ PubMed]
-# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3815266 PubMed]
-# Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2649221 PubMed]
-==Chlorambucil & Prednisolone {{#subobject:2cde9a|Regimen=1}}==
+=[[Head and neck cancer]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==EORTC 24954==
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:0044a9|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://jamanetwork.com/journals/jama/article-abstract/1163685 Freckman et al. 1964]
-| style="background-color:#91cf61" |Non-randomized
-|-
-|}
-====Chemotherapy====
-*[[Chlorambucil (Leukeran)]]
-====Hormonotherapy====
-*[[Prednisolone (Millipred)]]
-===References===
-# Freckman HA, Fry HL, Mendez FL, Maurer ER. Chlorambucil-prednisolone therapy for disseminated breast carcinoma. JAMA. 1964 Jul 6;189:23-6. [https://jamanetwork.com/journals/jama/article-abstract/1163685 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14149018 PubMed]
-==CHUT, then auto HSCT {{#subobject:e9e363|Regimen=1}}==
+===Arm 1, control===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|CF]] x 4, then [[Head_and_neck_cancer#Radiation_therapy|RT]]
+===Arm 2, experimental===
+*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29_.26_RT|CF/RT]]
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Sequential RT
-|}
+| style="background-color:#ffffbf" |Seems not superior
-===Regimen {{#subobject:392c1c|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nature.com/articles/1705935 Biron et al. 2007 (Pegase 03)]
+|Alternating RT
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#ffffbf" |Seems not superior
-|No further treatment
-| style="background-color:#1a9850" |Superior DFS
 |-
 |}
-====Preceding treatment====
-*[[Breast_cancer#FEC_3|FEC]] x 4
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 6000 mg/m<sup>2</sup>
-*[[Thiotepa (Thioplex)]] 800 mg/m<sup>2</sup>
 ===References===
-# '''Pegase 03:''' Biron P, Durand M, Roché H, Delozier T, Battista C, Fargeot P, Spaeth D, Bachelot T, Poiget E, Monnot F, Tanguy ML, Curé H. Pegase 03: a prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer. Bone Marrow Transplant. 2008 Mar;41(6):555-62. Epub 2007 Nov 26. [https://www.nature.com/articles/1705935 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18037940 PubMed]
+# Lefebvre JL, Rolland F, Tesselaar M, Bardet E, Leemans CR, Geoffrois L, Hupperets P, Barzan L, de Raucourt D, Chevalier D, Licitra L, Lunghi F, Stupp R, Lacombe D, Bogaerts J, Horiot JC, Bernier J, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Head and Neck Cancer Cooperative Group; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009 Feb 4;101(3):142-52. Epub 2009 Jan 27. [https://doi.org/10.1093/jnci/djn460 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724854/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19176454/ PubMed]
-==CMFP {{#subobject:d1eccf|Regimen=1}}==
+==RTOG 91-11==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Arm 1, induction chemotherapy, then radiotherapy (Control)===
+*[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|PF]] x 3, then [[Head_and_neck_cancer#Radiation_therapy|RT]]
+===Arm 2, concurrent chemoradiotherapy (Experimental)===
+*[[Head_and_neck_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
+===Arm 3, radiotherapy (Experimental)===
+*[[Head_and_neck_cancer#Radiation_therapy|RT]]
+===Comparative efficacy===
+''Efficacy is based on the 2012 update.''
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen vs.'''
+!'''Arm 1'''
+!'''Arm 2'''
+!'''Arm 3'''
 |-
-|[[#top|back to top]]
+|Arm 1 vs.
-|}
+| style="background-color:#d3d3d3" |
-CMFP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
+| style="background-color:#d73027" |Inferior LFS
-===Regimen {{#subobject:6c96a9|Variant=1}}===
+| style="background-color:#91cf60" |Seems to have superior LFS
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633086/ Canellos et al. 1974]
+|Arm 2 vs.
-| style="background-color:#91cf61" |Non-randomized
+| style="background-color:#1a9850" |Superior LFS
 | style="background-color:#d3d3d3" |
+| style="background-color:#91cf60" |Seems to have superior LFS
+|-
+|Arm 3 vs.
+| style="background-color:#fc8d59" |Seems to have inferior LFS
+| style="background-color:#fc8d59" |Seems to have inferior LFS
 | style="background-color:#d3d3d3" |
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L Tormey et al. 1982 (ECOG E2173)]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|1. AV<br> 2. [[Breast_cancer#CMF_2|CMF]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://link.springer.com/article/10.1007/BF01806026 Segaloff et al. 1985]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#CMFVP_2|CMFVP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1985.3.7.932 Cummings et al. 1985]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#FAC_3|CAF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F Marschke et al. 1989]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#CFP_2|CFP]]
-| style="background-color:#d9ef8b" |Might have superior ORR
-|-
-|[https://ascopubs.org/doi/10.1200/JCO.1999.17.8.2355 Bishop et al. 1999]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer#Paclitaxel_monotherapy.2C_q3wk|Paclitaxel]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
-====Chemotherapy====
+===References===
-*[[Cyclophosphamide (Cytoxan)]]
+# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [https://doi.org/10.1056/NEJMoa031317 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14645636/ PubMed]
-*[[Methotrexate (MTX)]]
+## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [https://doi.org/10.1200/jco.2012.43.6097 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23182993/ PubMed]
-*[[Fluorouracil (5-FU)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
-===References===
+=[[Classical Hodgkin lymphoma]]=
-# Canellos GP, Devita VT, Gold GL, Chabner BA, Schein PS, Young RC. Cyclical combination chemotherapy for advanced breast carcinoma. Br Med J. 1974 Feb 9;1(5901):218-20. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633086/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/4818162 PubMed]
+==EORTC-GELA H8-F==
-# '''ECOG E2173:''' Tormey DC, Gelman R, Band PR, Sears M, Rosenthal SN, DeWys W, Perlia C, Rice MA. Comparison of induction chemotherapies for metastatic breast cancer: an Eastern Cooperative Oncology Group Trial. Cancer. 1982 Oct 1;50(7):1235-44. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19821001)50:7%3C1235::AID-CNCR2820500703%3E3.0.CO;2-L link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7049347 PubMed]
-# Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. [https://link.springer.com/article/10.1007/BF01806026 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3896353 PubMed]
-# Cummings FJ, Gelman R, Horton J. Comparison of CAF versus CMFP in metastatic breast cancer: analysis of prognostic factors. J Clin Oncol. 1985 Jul;3(7):932-40. [https://ascopubs.org/doi/abs/10.1200/JCO.1985.3.7.932 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3894587 PubMed]
-# Marschke RF Jr, Ingle JN, Schaid DJ, Krook JE, Mailliard JA, Cullinan SA, Pfeifle DM, Votava HJ, Ebbert LP, Windschitl HE. Randomized clinical trial of CFP versus CMFP in women with metastatic breast cancer. Cancer. 1989 May 15;63(10):1931-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19890515)63:10%3C1931::AID-CNCR2820631011%3E3.0.CO;2-F link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2649221 PubMed]
-# Bishop JF, Dewar J, Toner GC, Smith J, Tattersall MH, Olver IN, Ackland S, Kennedy I, Goldstein D, Gurney H, Walpole E, Levi J, Stephenson J, Canetta R. Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer. J Clin Oncol. 1999 Aug;17(8):2355-64. [https://ascopubs.org/doi/10.1200/JCO.1999.17.8.2355 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10561297 PubMed]
-==CMFV {{#subobject:e18ffa|Regimen=1}}==
+===Arm 1===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Classical_Hodgkin_lymphoma#MOPP-ABV|MOPP-ABV]] x 3, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
+===Arm 2===
+*[[Classical_Hodgkin_lymphoma#Radiotherapy|STNI]]
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|MOPP-ABV x 3, then IFRT
-|}
+|style="background-color:#1a9850"|Superior OS
-CMFV: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''inblastine
-<br>CVMF: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''inblastine, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:405835|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.sciencedirect.com/science/article/pii/S0140673675906765 Edelstyn et al. 1975]
+|STNI
-|style="background-color:#1a9851" |Randomized (E-esc)
+|style="background-color:#d73027"|Inferior OS
-|[[#CMFV|CMFV]]; 1-day
-| style="background-color:#1a9850" |Superior ORR
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D Bezwoda et al. 1979]
-|style="background-color:#1a9851" |Randomized (C)
-|[[#CAMF|CAMF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-*[[Vincristine (Oncovin)]]
 ===References===
-# Edelstyn GA, Bates TD, Brinkley D, MacRae KD, Spittle MF, Wheeler T. Comparison of 5-day, 1-day, and 2-day cyclical combination chemotherapy in advanced breast cancer. Lancet. 1975 Aug 2;2(7927):209-11. [https://www.sciencedirect.com/science/article/pii/S0140673675906765 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/51964 PubMed]
+# Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; [[Study_Groups#EORTC|EORTC]]; GELA. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. [https://doi.org/10.1056/NEJMoa064601 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/17989384/ PubMed]
-# Bezwoda WR, de Moor NG, Derman D, Lange M, Saner R, Dando R. Combination chemotherapy of metastatic breast cancer: a randomized trial comparing the use of adriamycin to that of Vinblastine. Cancer. 1979 Aug;44(2):392-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197908)44:2%3C392::AID-CNCR2820440204%3E3.0.CO;2-D link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/383254 PubMed]
+==EORTC-GELA H8-U==
-==CMFVP {{#subobject:9920da|Regimen=1}}==
+===Arm 1===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+*[[Classical_Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 4, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
+===Arm 2===
+*[[Classical_Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 4, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|STNI]]
+===Arm 3 (control)===
+*[[Classical_Hodgkin_lymphoma#MOPP-ABV_2|MOPP-ABV]] x 6, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]]
+===Comparative efficacy===
+''Note: the paper describes this as an equivalence study, although the primary endpoint of EFS had p=0.80.''
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|MOPP-ABV x 4, then IFRT
-|}
+|style="background-color:#ffffbf"|Inconclusive whether equivalent
-CMFVP: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
-<br>COMFP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone
-<br>CFPMV: '''<u>C</u>'''yclophosphamide, '''<u>F</u>'''luorouracil, '''<u>P</u>'''rednisone, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''incristine
-===Regimen {{#subobject:e01cbf|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M Smalley et al. 1977]
+|MOPP-ABV x 4, then STNI
-|style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#ffffbf"|Inconclusive whether equivalent
-|[[Breast_cancer#FAC_3|CAF]]
-| style="background-color:#fee08b" |Might have inferior OS (*)
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 Muss et al. 1978]
+|MOPP-ABV x 6, then IFRT
-|style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#ffffbf"|Inconclusive whether equivalent
-|[[#CAFVP|CAFVP]]
-| style="background-color:#fee08b" |Might have inferior OS
-|-
-|[https://link.springer.com/article/10.1007/BF01806026 Segaloff et al. 1985]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#CMFP_2|CMFP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O Rosner et al. 1987]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|1. [[Breast_cancer#AC_3|CA]]<br> 2. [[#CFP_2|CFP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''Note: reported efficacy for Smalley et al. 1977 is based on the 1983 update.''
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Methotrexate (MTX)]]
-*[[Fluorouracil (5-FU)]]
-*[[Vincristine (Oncovin)]]
-====Hormonotherapy====
-*[[Prednisone (Sterapred)]]
 ===References===
-# Smalley RV, Carpenter J, Bartolucci A, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone (CMFVP) in patients with metastatic breast cancer: a Southeastern Cancer Study Group project. Cancer. 1977 Aug;40(2):625-32. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197708)40:2%3C625::AID-CNCR2820400206%3E3.0.CO;2-M link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/329975 PubMed]
+# Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; [[Study_Groups#EORTC|EORTC]]-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. [https://doi.org/10.1056/NEJMoa064601 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/17989384/ PubMed]
-## '''Update:''' Smalley RV, Lefante J, Bartolucci A, Carpenter J, Vogel C, Krauss S. A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer. Breast Cancer Res Treat. 1983;3(2):209-20. [https://link.springer.com/article/10.1007/BF01803563 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6688538 PubMed]
-# Muss HB, White DR, Richards F 2nd, Cooper MR, Stuart JJ, Jackson DV, Rhyne L, Spurr CL. Adriamycin versus methotrexate in five-drug combination chemotherapy for advanced breast cancer: a randomized trial. Cancer. 1978 Nov;42(5):2141-8. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197811)42:5%3C2141::AID-CNCR2820420509%3E3.0.CO;2-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/363253 PubMed]
-# Segaloff A, Hankey BF, Carter AC, Escher GC, Ansfield FJ, Talley RW. An evaluation of the effect of vincristine added to cyclophosphamide, 5-fluorouracil, methotrexate, and prednisone in advanced breast cancer. Breast Cancer Res Treat. 1985;5(3):311-9. [https://link.springer.com/article/10.1007/BF01806026 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3896353 PubMed]
-# Rosner D, Nemoto T, Lane WW. A randomized study of intensive versus moderate chemotherapy programs in metastatic breast cancer. Cancer. 1987 Mar 1;59(5):874-83. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19870301)59:5%3C874::AID-CNCR2820590503%3E3.0.CO;2-O link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3815266 PubMed]
-==DES monotherapy {{#subobject:0a1860|Regimen=1}}==
+==EORTC/LYSA/FIL H10==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+''Note: randomization in this trial occurred before treatment, but took effect after 2 cycles of ABVD, and only if interim PET-CT was negative.''
+===Arm 1===
+*Favorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 4
+*Unfavorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 6
+===Arm 2===
+*Favorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 3, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|INRT]]
+*Unfavorable: [[Classical_Hodgkin_lymphoma#ABVD|ABVD]] x 4, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|INRT]]
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|ABVD x 4
-|}
+|style="background-color:#ffffbf"|Inconclusive whether non-inferior
-===Regimen {{#subobject:128a40|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pubmed/14285946 Kennedy 1965]
-| style="background-color:#1a9851" |Randomized (E-switch-ic)
-|Testosterone
-| style="background-color:#d3d3d3" |Not available
-|-
-|[https://jamanetwork.com/journals/jama/article-abstract/353009 Carter et al. 1977]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[#DES_monotherapy|DES]]; other dosings
-| style="background-color:#d3d3d3" |See paper
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198101013040104 Ingle et al. 1981]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19810201)47:3%3C452::AID-CNCR2820470305%3E3.0.CO;2-Y Kiang et al. 1981]
+|ABVD x 3, then INRT
-| style="background-color:#1a9851" |Phase III (C)
+|style="background-color:#ffffbf"|Inconclusive whether non-inferior
-|Cyclophosphamide, 5-FU, DES
-| style="background-color:#fc8d59" |Seems to have inferior OS (*)
 |-
 |}
-''No longer used, but of historical interest. Reported efficacy for Kiang et al. 1981 is based on the 1985 update.''
-====Hormonotherapy====
-*[[Diethylstilbestrol (DES)]]
 ===References===
-# Kennedy BJ. Diethylstilbestrol versus testosterone propionate therapy in advanced breast cancer. Surg Gynecol Obstet. 1965 Jun;120:1246-50. [https://www.ncbi.nlm.nih.gov/pubmed/14285946 PubMed]
+# Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. [https://doi.org/10.1200/jco.2013.51.9298 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24637998/ PubMed]
-# Carter AC, Sedransk N, Kelley RM, Ansfield FJ, Ravdin RG, Talley RW, Potter NR. Diethylstilbestrol: recommended dosages for different categories of breast cancer patients: report of the Cooperative Breast Cancer Group. JAMA. 1977 May 9;237(19):2079-8. [https://jamanetwork.com/journals/jama/article-abstract/353009 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/576887 PubMed]
+## '''Update:''' André MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M, Casasnovas O, Brice P, van der Maazen R, Re A, Edeline V, Fermé C, van Imhoff G, Merli F, Bouabdallah R, Sebban C, Specht L, Stamatoullas A, Delarue R, Fiaccadori V, Bellei M, Raveloarivahy T, Versari A, Hutchings M, Meignan M, Raemaekers J. Early positron emission tomography response-adapted treatment in stage I and II Hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2017 Jun 1;35(16):1786-1794. Epub 2017 Mar 14. [https://doi.org/10.1200/JCO.2016.68.6394 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28291393/ PubMed]
-# Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981 Jan 1;304(1):16-21. [https://www.nejm.org/doi/full/10.1056/NEJM198101013040104 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7001242 PubMed]
-# Kiang DT, Frenning DH, Gay J, Goldman AI, Kennedy BJ. Combination therapy of hormone and cytotoxic agents in advanced breast cancer. Cancer. 1981 Feb 1;47(3):452-6. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19810201)47:3%3C452::AID-CNCR2820470305%3E3.0.CO;2-Y link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7013960 PubMed]
-## '''Update:''' Kiang DT, Gay J, Goldman A, Kennedy BJ. A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer. N Engl J Med. 1985 Nov 14;313(20):1241-6. [https://www.nejm.org/doi/full/10.1056/NEJM198511143132001 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3903501 PubMed]
-==CTCb, then auto HSCT {{#subobject:02f569|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CTCb: '''<u>C</u>'''yclophosphamide, '''<u>T</u>'''hiotepa, '''<u>C</u>'''ar'''<u>b</u>'''oplatin
-===Regimen {{#subobject:3dea9c|Variant=1}}===
+==GHSG HD17==
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM200004133421501 Stadtmauer et al. 2000]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[Breast_cancer#CMF_2|CMF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|}
-''No longer used, but of historical interest.''
-====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]]
-*[[Thiotepa (Thioplex)]]
-*[[Carboplatin (Paraplatin)]]
-===References===
+===Arm 1 (Control)===
-# Stadtmauer EA, O'Neill A, Goldstein LJ, Crilley PA, Mangan KF, Ingle JN, Brodsky I, Martino S, Lazarus HM, Erban JK, Sickles C, Glick JH; Philadelphia Bone Marrow Transplant Group. Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. N Engl J Med. 2000 Apr 13;342(15):1069-76. [https://www.nejm.org/doi/full/10.1056/NEJM200004133421501 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10760307 PubMed]
+*[[Classical_Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 3000 cGy
+===Arm 2 (Experimental)===
+*PET4 positive: [[Classical_Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|IFRT]] x 3000 cGy
+*PET4 negative: [[Classical_Hodgkin_lymphoma#eBEACOPP|eBEACOPP]] x 2, then [[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2
-==Estradiol monotherapy {{#subobject:edd4bd|Regimen=1}}==
+===Comparative efficacy===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 40%; text-align:center;"
+!style="width: 50%"|Chemotherapy
+!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|2+2 -> IFRT
-|}
+| style="background-color:#eeee01" |Non-inferior PFS
-===Variant #1, 6 mg/day {{#subobject:8e8202|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ Ellis et al. 2009]
+|PET-guided therapy
-| style="background-color:#1a9851" |Randomized Phase II (E-de-esc)
+| style="background-color:#eeee01" |Non-inferior PFS
-|[[#Estradiol_monotherapy|Estradiol]]; 30 mg/day
-| style="background-color:#ffffbf" |Did not meet primary endpoint of CBR
 |-
 |}
-====Hormonotherapy====
+===References===
-*[[Estradiol]] 6 mg PO once per day
+# Borchmann P, Plütschow A, Kobe C, Greil R, Meissner J, Topp MS, Ostermann H, Dierlamm J, Mohm J, Thiemer J, Sökler M, Kerkhoff A, Ahlborn M, Halbsguth TV, Martin S, Keller U, Balabanov S, Pabst T, Vogelhuber M, Hüttmann A, Wilhelm M, Zijlstra JM, Moccia A, Kuhnert G, Bröckelmann PJ, von Tresckow B, Fuchs M, Klimm B, Rosenwald A, Eich H, Baues C, Marnitz S, Hallek M, Diehl V, Dietlein M, Engert A. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):223-234. [https://doi.org/10.1016/s1470-2045(20)30601-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/33539742/ PubMed] [https://clinicaltrials.gov/study/NCT01356680 NCT01356680]
-'''Continued indefinitely'''
+==NCIC-CTG/ECOG HD.6==
-===Variant #2, 30 mg/day {{#subobject:8fahc02|Variant=1}}===
+''Note: this randomization was for patients with unfavorable risk.''
-{| class="wikitable" style="width: 100%; text-align:center;"
+===Arm 1===
-!style="width: 25%"|Study
+*[[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 4
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+===Arm 2===
-!style="width: 25%"|Comparator
+*[[Classical_Hodgkin_lymphoma#ABVD_2|ABVD]] x 2, then [[Classical_Hodgkin_lymphoma#Radiotherapy_2|STNI]]
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+===Comparative efficacy===
+''Efficacy is based on the 2011 update.''
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ Ellis et al. 2009]
+|ABVD x 4
-| style="background-color:#1a9851" |Randomized Phase II (C)
+|style="background-color:#91cf60"|Seems to have superior OS
-|[[#Estradiol_monotherapy|Estradiol]]; 6 mg/day
+|-
-| style="background-color:#ffffbf" |Did not meet primary endpoint of CBR
+|ABVD x 2, then STNI
+|style="background-color:#fc8d59"|Seems to have inferior OS
 |-
 |}
-====Hormonotherapy====
-*[[Estradiol]] 30 mg PO once per day
-'''Continued indefinitely'''
 ===References===
-# Ellis MJ, Gao F, Dehdashti F, Jeffe DB, Marcom PK, Carey LA, Dickler MN, Silverman P, Fleming GF, Kommareddy A, Jamalabadi-Majidi S, Crowder R, Siegel BA. Lower-dose vs high-dose oral estradiol therapy of hormone receptor-positive, aromatase inhibitor-resistant advanced breast cancer: a phase 2 randomized study. JAMA. 2009 Aug 19;302(7):774-80. [https://jamanetwork.com/journals/jama/fullarticle/184425 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460383/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19690310 PubMed]
+# Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Bezjak A, Wells WA, Burns BF, Winter JN, Horning SJ, Dar AR, Djurfeldt MS, Ding K, Shepherd LE; National Cancer Institute of Canada Clinical Trials Group; [[Study_Groups#ECOG|ECOG]]. Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group. J Clin Oncol. 2005 Jul 20;23(21):4634-42. Epub 2005 Apr 18. [https://doi.org/10.1200/JCO.2005.09.085 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15837968/ PubMed]
+## '''Update:''' Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; [[Study_Groups#ECOG|ECOG]]. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. [https://doi.org/10.1056/NEJMoa1111961 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22149921/ PubMed]
-==Fluoxymesterone monotherapy {{#subobject:835187|Regimen=1}}==
+=[[Mantle cell lymphoma]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==MCL Younger==
+===Arm 1 (Control)===
+*[[Mantle_cell_lymphoma#R-CHOP|R-CHOP]] x 6, then [[Stem_cell_mobilization#DexaBEAM_.26_G-CSF|Dexa-BEAM]], then [[Mantle_cell_lymphoma#Cyclophosphamide_.26_TBI.2C_then_auto_HSCT|Cy/TBI auto HSCT]]
+===Arm 2 (Experimental)===
+*[[Mantle_cell_lymphoma#R-CHOP.2FR-DHAP|R-CHOP/R-DHAP]] x 6, then cytarabine, melphalan, TBI auto HSCT
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 50%"|Regimen
+!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|SOC
-|}
+| style="background-color:#fc8d59" |Seems to have inferior TTTF
-===Regimen {{#subobject:1914f4|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM195810022591404 Kennedy 1958]
+|Cytarabine-based
-| style="background-color:#91cf61" |Non-randomized
+|style="background-color:#91cf60"|Seems to have superior TTTF
 |-
 |}
-====Hormonotherapy====
-*[[Fluoxymesterone (Halotestin)]]
 ===References===
-# Kennedy BJ. Fluoxymesterone therapy in advanced breast cancer. N Engl J Med. 1958 Oct 2;259(14):673-5. [https://www.nejm.org/doi/full/10.1056/NEJM195810022591404 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/13590423 PubMed]
+# Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. Epub 2016 Jun 14. [https://doi.org/10.1016/S0140-6736(16)00739-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/27313086/ PubMed]
+##'''Update:''' Hermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, Pott C, Salles G, Feugier P, Hübel K, Haioun C, Casasnovas RO, Schmidt C, Bouabdallah K, Ribrag V, Kanz L, Dürig J, Metzner B, Sibon D, Cheminant M, Burroni B, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Dreyling M; European Mantle Cell Lymphoma Network. High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023 Jan 20;41(3):479-484. Epub 2022 Dec 5. [https://doi.org/10.1200/jco.22.01780 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36469833/ PubMed]
-==Formestane monotherapy {{#subobject:6c7bb9|Regimen=1}}==
+=[[Multiple myeloma]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==HOVON-50==
-|-
+===Arm 1 (Control)===
-|[[#top|back to top]]
+*[[Multiple_myeloma_-_historical#VAD|VAD]], then [[Stem_cell_mobilization#CAD_.26_G-CSF|CAD & G-CSF stem cell mobilization]], then [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan_monotherapy.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT, then [[Multiple_myeloma_-_historical#Interferon_alfa_monotherapy|interferon alfa]] maintenance
-|}
+===Arm 2 (Experimental)===
-===Regimen {{#subobject:8b5e67|Variant=1}}===
+*[[Multiple_myeloma,_induction#TAD_.28Thalidomide.29|TAD]] x 3, then [[Stem_cell_mobilization#CAD_.26_G-CSF|CAD & G-CSF stem cell mobilization]], then [[Multiple_myeloma,_consolidation_and_maintenance#Melphalan_monotherapy.2C_then_auto_HSCT|single]] or [[Multiple_myeloma,_consolidation_and_maintenance#Tandem_melphalan.2C_then_auto_HSCT|tandem]] melphalan auto HSCT, then [[Multiple_myeloma,_consolidation_and_maintenance#Thalidomide_monotherapy|thalidomide]] maintenance
-{| class="wikitable" style="width: 100%; text-align:center;"
+===Comparative efficacy===
-!style="width: 25%"|Study
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 50%"|Regimen
-!style="width: 25%"|Comparator
+!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)92795-8/fulltext Coombes et al. 1984]
+|SOC
-| style="background-color:#ffffbe" |Pilot
+| style="background-color:#d73027" |Inferior PFS
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
-|[https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf Thürlimann et al. 1997 (SAKK 20/90)]
+|Thalidomide-based
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9850" |Superior PFS
-|[[#Megestrol_monotherapy|Megestrol]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 |-
 |}
-====Hormonotherapy====
-*[[Formestane (Lentaron)]]
 ===References===
-# Coombes RC, Goss P, Dowsett M, Gazet JC, Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237-9. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)92795-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6150277 PubMed]
+# Lokhorst HM, van der Holt B, Zweegman S, Vellenga E, Croockewit S, van Oers MH, von dem Borne P, Wijermans P, Schaafsma R, de Weerdt O, Wittebol S, Delforge M, Berenschot H, Bos GM, Jie KS, Sinnige H, van Marwijk-Kooy M, Joosten P, Minnema MC, van Ammerlaan R, Sonneveld P; Dutch-Belgian Hemato-Oncology Group (HOVON). A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010 Feb 11;115(6):1113-20. Epub 2009 Oct 30. [https://doi.org/10.1182/blood-2009-05-222539 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19880501/ PubMed]
-# '''SAKK 20/90:''' Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research (SAKK). Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. [https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9376181 PubMed]
+## '''Update:''' van de Donk NW, van der Holt B, Minnema MC, Vellenga E, Croockewit S, Kersten MJ, von dem Borne PA, Ypma P, Schaafsma R, de Weerdt O, Klein SK, Delforge M, Levin MD, Bos GM, Jie KG, Sinnige H, Coenen JL, de Waal EG, Zweegman S, Sonneveld P, Lokhorst HM. Thalidomide before and after autologous stem cell transplantation in recently diagnosed multiple myeloma (HOVON-50): long-term results from the phase 3, randomised controlled trial. Lancet Haematol. 2018 Oct;5(10):e479-e492. [https://doi.org/10.1016/S2352-3026(18)30149-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290905/ PubMed]
-==Medroxyprogesterone monotherapy {{#subobject:6c7bb9|Regimen=1}}==
+=[[Non-small cell lung cancer]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==ECOG 3598==
+===Arm 1 (Control)===
+*[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_.28CP.29_2|PC]] induction, then [[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|Carboplatin, Paclitaxel, RT]]
+===Arm 2, with thalidomide (Experimental)===
+*TPC, then Carboplatin, Paclitaxel, Thalidomide, RT
+===Comparative efficacy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Without thalidomide
-|}
+|style="background-color:#ffffbf"|Seems not superior
-===Variant #1, 500 mg/day {{#subobject:8b5e67|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://journals.sagepub.com/doi/abs/10.1177/030089167806400204 Cuna et al. 1978]
+|With thalidomide
-|style="background-color:#1a9851"|Phase III (E-de-esc)
+|style="background-color:#ffffbf"|Seems not superior
-|[[#Medroxyprogesterone_monotherapy|MPA]]; 1000 mg/day
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
-|-
-|[https://www.ejcancer.com/article/0014-2964(79)90097-5/abstract Pannuti et al. 1979]
-|style="background-color:#1a9851"|Phase III (C)
-|[[#Medroxyprogesterone_monotherapy|MPA]]; 1500 mg/day
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
-|-
-|[https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 Canney et al. 1988]
-|style="background-color:#1a9851"|Phase III (C)
-|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.9.3141 Byrne et al. 1997 (ANZ8613)]
-|style="background-color:#1a9851"|Phase III (C)
-|MPA & Tamoxifen
-|style="background-color:#ffffbf"|Did not meet primary endpoint of TTP
 |-
 |}
-''Note: Canney et al. 1988 does not have dosing information in the abstract.''
+===References===
-====Hormonotherapy====
+# Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.9116 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22271472/ PubMed]
-*[[Medroxyprogesterone (MPA)]] 500 mg PO once per day
-'''Continued indefinitely'''
+==IUNO==
-===Variant #2, 900 mg/day {{#subobject:88ge67|Variant=1}}===
+===Arm 1, "early" erlotinib===
-{| class="wikitable" style="width: 100%; text-align:center;"
+*[[Non-small_cell_lung_cancer#Erlotinib_monotherapy|Maintenance erlotinib]]
-!style="width: 25%"|Study
+===Arm 2, "late" erlotinib===
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+*[[Non-small_cell_lung_cancer#Placebo_3|Placebo]] until progression or intolerance, then [[Non-small_cell_lung_cancer#Erlotinib_monotherapy_2|erlotinib]]
-!style="width: 25%"|Comparator
+===Comparative efficacy===
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Timing'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
+|-
+|Maintenance erlotinib
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 van Veelen et al. 1986]
+|Second-line erlotinib
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 |-
 |}
-====Hormonotherapy====
+===References===
-*[[Medroxyprogesterone (MPA)]] 300 mg PO three times per day
+# Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. [https://doi.org/10.1016/j.lungcan.2016.10.007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27987585/ PubMed]
-'''Continued indefinitely'''
+==RTOG 9410==
-===Variant #3, 1000 mg/day (high-dose) {{#subobject:62af61|Variant=1}}===
+===Arm 1, sequential (control)===
-{| class="wikitable" style="width: 100%; text-align:center;"
+*[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]], then [[Non-small_cell_lung_cancer#Radiation_therapy|RT]]
-!style="width: 25%"|Study
+===Arm 2, concurrent (experimental)===
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+*[[Non-small_cell_lung_cancer#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]]
-!style="width: 25%"|Comparator
+===Arm 3, concurrent (experimental)===
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+*[[Non-small_cell_lung_cancer#Cisplatin.2C_Vinblastine.2C_RT|Cisplatin, Vinblastine, RT]]
-|-
+===Comparative efficacy===
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.5.414 Cavalli et al. 1984]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|style="background-color:#1a9851"|Phase III (E-esc)
+!'''Schedule'''
-|[[#Medroxyprogesterone_monotherapy|MPA]]; low-dose
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-| style="background-color:#1a9850" |Superior ORR
-|-
-|[https://link.springer.com/article/10.1007/BF01961246 Garcia-Giralt et al. 1992]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
-| style="background-color:#fc8d59" |Seems to have inferior TTP
 |-
-|[https://academic.oup.com/annonc/article-abstract/4/9/735/170824 Castiglione-Gertsch et al. 1993]
+|Concurrent
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+|style="background-color:#91cf60"|Seems to have superior OS
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-| style="background-color:#d9ef8b" |Might have superior TTP
 |-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1994.12.8.1630 Muss et al. 1994]
+|Sequential
-|style="background-color:#1a9851"|Phase III (E-switch-ic)
+|style="background-color:#fc8d59"|Seems to have inferior OS
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-| style="background-color:#d9ef8b" |Might have superior OS
 |-
 |}
-====Hormonotherapy====
+===References===
-*[[Medroxyprogesterone (MPA)]] 1000 mg PO or IM once per day
+# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [https://doi.org/10.1093/jnci/djr325 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21903745/ PubMed]
-**Garcia-Giralt et al. 1992 gave as 500 mg PO twice per day
-'''Continued indefinitely'''
+=[[Ovarian cancer]]=
+==GOG 114==
-===References===
+===Arm 1 - Control===
-# Cuna GR, Calciati A, Strada MR, Bumma C, Campio L. High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. Tumori. 1978 Apr 30;64(2):143-9. [https://journals.sagepub.com/doi/abs/10.1177/030089167806400204 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/354147 PubMed]
+*[[Ovarian_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] x 6
-# Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, Becchi G, Mattioli G, Barbanti F, Marra GA, Persiani W, Cacciari L, Spagnolo F, Palenzona D, Rocchetta G. Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. Eur J Cancer. 1979 Apr;15(4):593-601. [https://www.ejcancer.com/article/0014-2964(79)90097-5/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/86447 PubMed]
+===Arm 2 - Experimental===
-# Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol. 1984 May;2(5):414-9. [https://ascopubs.org/doi/abs/10.1200/JCO.1984.2.5.414 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6233398 PubMed]
+*[[Ovarian_cancer#Carboplatin_monotherapy|Carboplatin]] AUC 9 x 2, then [[Ovarian_cancer#IP_Cisplatin_.26_Paclitaxel|IP Cisplatin & IV Paclitaxel]] x 6
-# van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7-13. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19860701)58:1%3C7::AID-CNCR2820580103%3E3.0.CO;2-%23 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2939943 PubMed]
+===Comparative efficacy===
-# Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. J Natl Cancer Inst. 1988 Sep 21;80(14):1147-51. [https://academic.oup.com/jnci/article-abstract/80/14/1147/908657 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2970555 PubMed]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-# Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P, Fumoleau P, Gorins A, Guerin D, Guerin R, Maillart P, Mauriac L, May-Levin F, Metz R, Namer M, Olivier JP, Pommatau E, Pouillart P, Pujade-Lauraine E, Rouesse J, Serrou B, Vitse M, Zylberait D. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Res Treat. 1992;24(2):139-45. [https://link.springer.com/article/10.1007/BF01961246 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8443401 PubMed]
+!style="width: 50%"|'''Regimen'''
-# Castiglione-Gertsch M, Pampallona S, Varini M, Cavalli F, Brunner K, Senn HJ, Goldhirsch A, Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?. Ann Oncol. 1993 Nov;4(9):735-40. [https://academic.oup.com/annonc/article-abstract/4/9/735/170824 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8280653 PubMed]
+!style="width: 50%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-# Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, Powell BL, Richards F, SPurr CL, Eagle K, White DR. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study. J Clin Oncol. 1994 Aug;12(8):1630-8. [https://ascopubs.org/doi/abs/10.1200/JCO.1994.12.8.1630 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8040675 PubMed]
-# '''ANZ8613:''' Byrne MJ, Gebski V, Forbes J, Tattersall MH, Simes RJ, Coates AS, Dewar J, Lunn M, Flower C, Gill PG, Stewart J; Australian-New Zealand Breast Cancer Trials Group. Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. J Clin Oncol. 1997 Sep;15(9):3141-8. [https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.9.3141 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9294477 PubMed]
-==Megestrol monotherapy {{#subobject:a806f8|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|Control
-|}
-===Regimen {{#subobject:27fd99|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1988.6.7.1098 Muss et al. 1988]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://link.springer.com/article/10.1007/BF01810736 Lundgren et al. 1989]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Aminoglutethimide_monotherapy|Aminoglutethimide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://ascopubs.org/doi/10.1200/jco.1990.8.11.1797 Muss et al. 1990]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Megestrol_monotherapy|Megestrol]]; higher-dose
 | style="background-color:#fc8d59" |Seems to have inferior OS
 |-
-|[https://academic.oup.com/annonc/article-abstract/4/9/741/170864 Gill et al. 1993]
+|Experimental
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#91cf60" |Seems to have superior OS
-|1. [[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]<br> 2. Megestrol & Tamoxifen
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|[https://www.ejcancer.com/article/0959-8049(95)00014-3/pdf Jonat et al. 1996]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]
-| style="background-color:#fc8d59" |Seems to have inferior OS (*)
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W Buzdar et al. 1996 (Protocol 03)]
-| style="background-color:#1a9851" |Phase III (C)
-|Fadrozole
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W Buzdar et al. 1996 (Protocol 06)]
-| style="background-color:#1a9851" |Phase III (C)
-|Fadrozole
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.2000 Buzdar et al. 1996a]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer,_ER-positive#Anastrozole_monotherapy_4|Anastrozole]]
-| style="background-color:#fc8d59" |Seems to have inferior OS (*)
-|-
-|[https://www.ejcancer.com/article/0959-8049(96)00191-8/pdf Stuart et al. 1996]
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|[https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf Thürlimann et al. 1997 (SAKK 20/90)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Formestane_monotherapy|Formestane]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.7.2494 Russell et al. 1997 (SWOG S8312)]
-| style="background-color:#1a9851" |Phase III (C)
-|Aminoglutethimide, Hydrocortisone, Megestrol
-| style="background-color:#ffffbf" |Seems not superior
-|-
-|rowspan=2|[https://ascopubs.org/doi/10.1200/JCO.1998.16.2.453 Dombernowsky et al. 1998]
-|rowspan=2 style="background-color:#1a9851"|Randomized (C)
-|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[[Breast_cancer,_ER-positive#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.1999.17.1.52 Goss et al. 1999]
-| style="background-color:#1a9851" |Phase III (C)
-|Vorozole
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://ascopubs.org/doi/10.1200/jco.1999.17.1.64 Abrams et al. 1999 (CALGB 8741)]
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Megestrol_monotherapy|Megestrol]]; higher-dose
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2000.18.7.1399 Kaufmann et al. 2000]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer,_ER-positive#Exemestane_monotherapy_3|Exemestane]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|-
-|[https://ascopubs.org/doi/full/10.1200/JCO.2001.19.14.3357 Buzdar et al. 2001]
-| style="background-color:#1a9851"|Phase III (C)
-|1. [[#Letrozole_monotherapy_4|Letrozole]]; 0.5 mg/day<br> 2. [[#Letrozole_monotherapy_4|Letrozole]]; 2.5 mg/day
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-''Note: Reported efficacy for Jonat et al. 1996 & Buzdar et al. 1996a is based on the 1998 pooled update.''
-====Hormonotherapy====
-*[[Megestrol (Megace)]] 160 mg PO once per day
-**Kaufmann et al. 2000 gave as 40 mg PO four times per day
-'''Continued indefinitely'''
 ===References===
-# Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Powell BL, Richards F, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan TM. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098-106. [https://ascopubs.org/doi/abs/10.1200/JCO.1988.6.7.1098 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3292710 PubMed]
+# Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. [https://doi.org/10.1200/JCO.2001.19.4.1001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11181662/ PubMed]
-# Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat. 1989 Nov;14(2):201-6. [https://link.springer.com/article/10.1007/BF01810736 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2690972 PubMed]
-# Muss HB, Case LD, Capizzi RL, Cooper MR, Cruz J, Jackson D, Richards F 2nd, Powell BL, Spurr CL, White D, Zekan P, Read S, Cates-Wilkie S, Bearden J, McCullough J, Callahan R, Karb K, Atkins J, Paschal B, Ramseur B, Lusk J, Stanley V. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1990 Nov;8(11):1797-805. [https://ascopubs.org/doi/10.1200/jco.1990.8.11.1797 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2230868 PubMed]
-# Gill PG, Gebski V, Snyder R, Burns I, Levi J, Byrne M, Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741-4. [https://academic.oup.com/annonc/article-abstract/4/9/741/170864 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8280654 PubMed]
-# Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, Tyrrell C, Mauriac L, Roche H, Lundgren S, Hellmund R, Azab M. A randomised trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996 Mar;32A(3):404-12. [https://www.ejcancer.com/article/0959-8049(95)00014-3/pdf link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8814682 PubMed]
-## '''Pooled update:''' Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.2000 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683230 PubMed]
-## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9740079 PubMed]
-# Buzdar AU, Smith R, Vogel C, Bonomi P, Keller AM, Favis G, Mulagha M, Cooper J. Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials. Cancer. 1996 Jun 15;77(12):2503-13. [https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1097-0142(19960615)77:12%3C2503::AID-CNCR13%3E3.0.CO;2-W link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8640699 PubMed]
-# Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV; Arimidex Study Group. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. J Clin Oncol. 1996 Jul;14(7):2000-11. [https://ascopubs.org/doi/abs/10.1200/JCO.1996.14.7.2000 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8683230 PubMed]
-## '''Update:''' Buzdar AU, Jones SE, Vogel CL, Wolter J, Plourde P, Webster A; Arimidex Study Group. A phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 Feb 15;79(4):730-9. [https://onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819970215%2979%3A4%3C730%3A%3AAID-CNCR10%3E3.0.CO%3B2-0 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9024711 PubMed]
-## '''Pooled update:''' Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL, Eiermann W, Wolter JM, Steinberg M, Webster A, Lee D; Arimidex Study Group. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Cancer. 1998 Sep 15;83(6):1142-52. Erratum in: Cancer 1999 Feb 15;85(4):1010. [https://onlinelibrary.wiley.com/doi/full/10.1002/%28SICI%291097-0142%2819980915%2983%3A6%3C1142%3A%3AAID-CNCR13%3E3.0.CO%3B2-5 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9740079 PubMed]
-# Stuart NS, Warwick J, Blackledge GR, Spooner D, Keen C, Taylor AR, Tyrell C, Webster DJ, Earl H. A randomised phase III cross-over study of tamoxifen versus megestrol acetate in advanced and recurrent breast cancer. Eur J Cancer. 1996 Oct;32A(11):1888-92. [https://www.ejcancer.com/article/0959-8049(96)00191-8/pdf link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8943670 PubMed]
-# '''SAKK 20/90:''' Thürlimann B, Castiglione M, Hsu-Schmitz SF, Cavalli F, Bonnefoi H, Fey MF, Morant R, Löhnert T, Goldhirsch A; Swiss Group for Clinical Cancer Research (SAKK). Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Eur J Cancer. 1997 Jun;33(7):1017-24. [https://www.ejcancer.com/article/S0959-8049(97)00105-6/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9376181 PubMed]
-# '''SWOG S8312:''' Russell CA, Green SJ, O'Sullivan J, Hynes HE, Budd GT, Congdon JE, Martino S, Osborne CK. Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial. J Clin Oncol. 1997 Jul;15(7):2494-501. [https://ascopubs.org/doi/abs/10.1200/JCO.1997.15.7.2494 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9215817 PubMed]
-# Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol. 1998 Feb;16(2):453-61. [https://ascopubs.org/doi/10.1200/JCO.1998.16.2.453 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9469328 PubMed]
-# Goss PE, Winer EP, Tannock IF, Schwartz LH; North American Vorozole Study Group. Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. J Clin Oncol. 1999 Jan;17(1):52-63. [https://ascopubs.org/doi/full/10.1200/JCO.1999.17.1.52 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10458218 PubMed]
-# '''CALGB 8741:''' Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, Norton L. Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and Leukemia Group B phase III study 8741. J Clin Oncol. 1999 Jan;17(1):64-73. [https://ascopubs.org/doi/10.1200/jco.1999.17.1.64 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10458219 PubMed]
-# Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G; The Exemestane Study Group. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000 Apr;18(7):1399-411. [https://ascopubs.org/doi/full/10.1200/JCO.2000.18.7.1399 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10735887 PubMed]
-# Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol. 2001 Jul 15;19(14):3357-66. [https://ascopubs.org/doi/full/10.1200/JCO.2001.19.14.3357 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11454883 PubMed]
-==Melphalan monotherapy {{#subobject:b913c5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-P: '''<u>P</u>'''henylalanine mustard (Melphalan)
-===Regimen {{#subobject:ab3663|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H Canellos et al. 1976]
-| style="background-color:#1a9851" |Phase III (C)
-|[[Breast_cancer#CMF_2|CMF]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|-
-|}
-====Chemotherapy====
-*[[Melphalan (Alkeran)]] 6 mg/m<sup>2</sup> PO once per day on days 1 to 5
-'''42-day cycles'''
+=[[Pancreatic cancer]]=
-===References===
+==GERCOR LAP07==
-# Canellos GP, Pocock SJ, Taylor SG 3rd, Sears ME, Klaasen DJ, Band PR. Combination chemotherapy for metastatic breast carcinoma: prospective comparison of multiple drug therapy with L-phenylalanine mustard. Cancer. 1976 Nov;38(5):1882-6. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197611)38:5%3C1882::AID-CNCR2820380503%3E3.0.CO;2-H link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/991103 PubMed]
-==Methotrexate & Thiotepa {{#subobject:c67a88|Regimen=1}}==
+''This study had two randomizations; the second only occurred if patients were progression-free after 4 cycles.''
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Arm 1 - Control===
+*[[Pancreatic_cancer#Gemcitabine_monotherapy_2|Gemcitabine]] x 6
+===Arm 2 - Experimental===
+*[[Pancreatic_cancer#Gemcitabine_monotherapy_2|Gemcitabine]] x 4, then Capecitabine & RT
+===Arm 3 - Experimental===
+*[[Pancreatic_cancer#Erlotinib_.26_Gemcitabine|Erlotinib & Gemcitabine]] x 6
+===Arm 4 - Experimental===
+*[[Pancreatic_cancer#Erlotinib_.26_Gemcitabine|Erlotinib & Gemcitabine]] x 4, then Capecitabine, Erlotinib, RT
+===Comparative efficacy===
+====First randomization====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Gemcitabine
-|}
+|style="background-color:#d9ef8b"|Might have superior OS
-===Regimen {{#subobject:4c1582|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pubmed/13950199 Greenspan et al. 1963]
+|With Erlotinib
-| style="background-color:#91cf61" |Non-randomized
+|style="background-color:#fee08b"|Might have inferior OS
 |-
 |}
-''Note: this is possibly the first published trial of combination chemotherapy in breast cancer.''
+====Second randomization====
-====Chemotherapy====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*[[Methotrexate (MTX)]]
+!'''Modality'''
-*[[Thiotepa (Tepadina)]]
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-===References===
-# Greenspan EM, Fieber M, Lesnick G, Edelman S. Response of advanced breast carcinoma to the combination of the antimetabolite, Methotrexate, and the alkylating agent, thio-TEPA. J Mt Sinai Hosp N Y. 1963 May-Jun;30:246-67. [https://www.ncbi.nlm.nih.gov/pubmed/13950199 PubMed]
-==Mitoxantrone monotherapy {{#subobject:c67f55|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|Chemotherapy
-|}
+|style="background-color:#ffffbf"|Seems not superior
-===Regimen {{#subobject:4c8527|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PII0140-6736(90)90277-C/fulltext Harris et al. 1990]
+|Chemoradiotherapy
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+|style="background-color:#ffffbf"|Seems not superior
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 Cowan et al. 1991 (SWOG S8203)]
-| style="background-color:#1a9851" |Phase III (C)
-|1. Bisantrene<br> 2. [[Breast_cancer#Doxorubicin_monotherapy_3|Doxorubicin]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
-====Chemotherapy====
-*[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycles'''
 ===References===
-# Harris AL, Cantwell BM, Carmichael J, Wilson R, Farndon J, Dawes P, Ghani S, Evans RG. Comparison of short-term and continuous chemotherapy (mitozantrone) for advanced breast cancer. Lancet. 1990 Jan 27;335(8683):186-90. [https://www.thelancet.com/journals/lancet/article/PII0140-6736(90)90277-C/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1967666 PubMed]
+# Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouché O, Shannon J, André T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: The LAP07 randomized clinical trial. JAMA. 2016 May 3;315(17):1844-53. [https://doi.org/10.1001/jama.2016.4324 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27139057/ PubMed]
-# '''SWOG S8203:''' Cowan JD, Neidhart J, McClure S, Coltman CA Jr, Gumbart C, Martino S, Hutchins LF, Stephens RL, Vaughan CB, Osborne CK. Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study. J Natl Cancer Inst. 1991 Aug 7;83(15):1077-84. [https://academic.oup.com/jnci/article-abstract/83/15/1077/882648 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1875415 PubMed]
-==STAMP-I {{#subobject:c08ab4|Regimen=1}}==
+=[[Rectal cancer]]=
-{| class="wikitable" style="float:right; margin-left: 5px;"
+==CinClare==
-|-
+===Arm 1 (Control)===
-|[[#top|back to top]]
+[[Rectal_cancer#Capecitabine_.26_RT|Capecitabine & RT]], then [[Rectal_cancer#CapeOx|CapeOx]] x 1, then TME, then CapeOx x 5
-|}
-===Regimen {{#subobject:7gy709|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.nature.com/articles/1705367 Vredenburgh et al. 2006]
-|style="background-color:#1a9851" |Phase III (E-esc)
-|Observation
-| style="background-color:#1a9850" |Superior EFS
-|-
-|}
-====Preceding treatment====
-*Duke AFM x 2 to 4
-====Chemotherapy====
-*[[Carmustine (BCNU)]]
-*[[Cisplatin (Platinol)]]
-*[[Cyclophosphamide (Cytoxan)]]
-===References===
+===Arm 2 (Experimental)===
-# Vredenburgh JJ, Madan B, Coniglio D, Ross M, Broadwater G, Niedzwiecki D, Edwards J, Marks L, Vandemark R, McDonald C, Affronti ML, Peters WP. A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy. Bone Marrow Transplant. 2006 Jun;37(11):1009-15. [https://www.nature.com/articles/1705367 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16633363 PubMed]
+Genotype-dosed CAPIRI & RT, then genotype-dosed CAPIRI x 1, then TME, then CapeOx x 5
-==TAD (Tamoxifen) {{#subobject:1ac555|Regimen=1}}==
+===Comparative efficacy===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!'''Regimen'''
+![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[[#top|back to top]]
+|Control
-|}
+| style="background-color:#d73027" |Inferior pCR rate
-TAD: '''<u>T</u>'''amoxifen, '''<u>A</u>'''minoglutethimide, '''<u>D</u>'''anazol
-===Regimen {{#subobject:0b2c27|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)91872-5/fulltext Powles et al. 1984]
+|Experimental
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9850" |Superior pCR rate
-|[[Breast_cancer,_ER-positive#Tamoxifen_monotherapy_2|Tamoxifen]]
-| style="background-color:#91cf60" |Seems to have superior ORR
 |-
 |}
-''Note: this patient population was not selected by hormone receptor status.''
-====Hormonotherapy====
-*[[Tamoxifen (Nolvadex)]]
-*[[Aminoglutethimide (Cytadren)]]
-*[[Danazol (Danocrine)]]
 ===References===
-# Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. Lancet. 1984 Jun 23;1(8391):1369-73. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)91872-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6145832 PubMed]
+#Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. [https://doi.org/10.1200/jco.20.01932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33119477/ PubMed] [https://clinicaltrials.gov/study/NCT02605265 NCT02605265]
-==Thiotepa monotherapy {{#subobject:123f55|Regimen=1}}==
+==RAPIDO==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Arm 1 (Control)===
-|-
+[[Rectal_cancer#Capecitabine_.26_RT|Capecitabine & RT]], then TME, then (per hospital policy) CapeOx x 8 or FOLFOX4 x 12
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:4a8d27|Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM195505262522101 Bateman 1955]
-| style="background-color:#91cf61" |Non-randomized
-|-
-|}
-====Chemotherapy====
-*[[Thiotepa (Thioplex)]]
-===References===
+===Arm 2 (Experimental)===
-# Bateman JC. Chemotherapy of solid tumors with triethylene thiophosphoramide. N Engl J Med. 1955 May 26;252(21):879-87. [https://www.nejm.org/doi/full/10.1056/NEJM195505262522101 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14370446 PubMed]
+[[Rectal_cancer#Radiation_therapy|RT]], then [[Rectal_cancer#CapeOx|CapeOx]] x 6 or [[Rectal_cancer#FOLFOX4|FOLFOX4]] x 9, then TME
-==VAC (Adriamycin) {{#subobject:90f8d0|Regimen=1}}==
+===Comparative efficacy===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|-
+!'''Regimen'''
-|[[#top|back to top]]
+![[Levels_of_Evidence#Efficacy|Efficacy]]
-|}
-VAC: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide
-===Regimen {{#subobject:4da860|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.sciencedirect.com/science/article/pii/0277537986900751 Gundersen et al. 1986]
+|RT, then chemo, then TME
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#91cf60" |Seems to have superior DRTF
-|[[Breast_cancer#Doxorubicin_monotherapy_2|Doxorubicin]]
-|style="background-color:#ffffbf"|Seems not superior
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977504/ Powles et al. 1991]
+|Chemo-RT, then TME, +/- adjuvant chemo
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#fc8d59" |Seems to have inferior DRTF
-|3M
-|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
-|-
-|[https://link.springer.com/article/10.1007/BF01806182 Green et al. 1996]
-|style="background-color:#1a9851"|Phase III (C)
-|VNC
-| style="background-color:#d9ef8b" |Might have superior ORR
 |-
 |}
-''Used as a comparator arm in older trials and found to be more toxic; here for reference purposes only.''
-====Chemotherapy====
-*[[Vincristine (Oncovin)]]
-*[[Doxorubicin (Adriamycin)]]
-*[[Cyclophosphamide (Cytoxan)]]
 ===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. [http://www.sciencedirect.com/science/article/pii/0277537986900751 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/3595668 PubMed]
+#Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. [https://doi.org/10.1016/s1470-2045(20)30555-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33301740/ PubMed]
-# Powles TJ, Jones AL, Judson IR, Hardy JR, Ashley SE. A randomised trial comparing combination chemotherapy using mitomycin C, mitozantrone and methotrexate (3M) with vincristine, anthracycline and cyclophosphamide (VAC) in advanced breast cancer. Br J Cancer. 1991 Aug;64(2):406-10. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977504/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1892775 PubMed]
-# Green JA, Slater AJ, Campbell IR, Kelly V. Advanced breast cancer: a randomized study of doxorubicin or mitoxantrone in combination with cyclophosphamide and vincristine. Breast Cancer Res Treat. 1996;39(2):155-63. [https://link.springer.com/article/10.1007/BF01806182 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8872324 PubMed]
-==VAP {{#subobject:4b99b8|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-VAP: '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin),  '''<u>P</u>'''rednisolone
-===Regimen {{#subobject:7d4b85|Variant=1}}===
-{| class="wikitable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|Comparator
-!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.7.1056 Leonard et al. 1987]
-|style="background-color:#1a9851"|Phase III (C)
-|VMP
-|style="background-color:#ffffbf"|Seems not superior
-|-
-|}
-====Chemotherapy====
-*[[Vincristine (Oncovin)]]
-*[[Doxorubicin (Adriamycin)]]
-====Hormonotherapy====
-*[[Prednisolone (Millipred)]]
-===References===
-# Leonard RC, Cornbleet MA, Kaye SB, Soukop M, White G, Hutcheon AW, Robinson S, Kerr ME, Smyth JF. Mitoxantrone versus doxorubicin in combination chemotherapy for advanced carcinoma of the breast. J Clin Oncol. 1987 Jul;5(7):1056-63. [https://ascopubs.org/doi/abs/10.1200/JCO.1987.5.7.1056 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/3298559 PubMed]
-[[Category:Breast cancer regimens]]
+[[Category:General reference pages]]
-[[Category:Historical regimens]]
-[[Category:Disease-specific pages]]
-[[Category:Solid tumors]]

Difference between revisions of "Complex multipart regimens"

Latest revision as of 12:07, 29 June 2024

COG AAML0531

References

UK MRC AML12

References

UK MRC AML15

References

C9710

Arm 1

Arm 2, with ATO3

Comparative efficacy

References

DBCG 82b

Arm 1 (Experimental)

Arm 2 (Control)

Comparative efficacy

References

Loesch et al. 2010

Arm 1, control

Arm 2, experimental

Comparative efficacy

References

Mavroudis et al. 2017

Arm 1, sequential

Arm 2, concurrent

Comparative efficacy

References

NeoALTTO

Arm 1, trastuzumab (C)

Arm 1, lapatinib (E)

Arm 3, lapatinib & trastuzumab (E)

Comparative efficacy

References

NOAH

Arm 1, no trastuzumab (Control)

Arm 2, with trastuzumab (Experimental)

Comparative efficacy

References

PREPARE

Arm 1, control

Arm 2, experimental

Comparative efficacy

References

Recht et al. 1996

Arm 1, chemo first

Arm 2, RT first

Comparative efficacy

References

SBG 9401

Arm 1 (control)

Arm 2 (experimental)

Comparative efficacy

References

SWOG-8814

Arm 1 (Control)

Arm 2, CAF-T (Experimental)

Arm 3, CAFT (Experimental)

Comparative efficacy

Comparison 1

Comparison 2

References

TRYPHAENA

Arm A

Arm B

Arm C

Comparative efficacy

References

Cervical cancer

NOGGO-AGO

Arm 1 (Control)

Arm 2 (Experimental)

Comparative efficacy

References

CAIRO

Arm 1, sequential single agent (Control)

Arm 2, sequential combinations (Experimental)

Comparative efficacy

References

FFCD 2000-05