Complex multipart regimens

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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 EuroPMC
==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 EuroPMC
==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 EuroPMC
=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	Shorter EFS
With ATO3 	Longer 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
=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 	Longer OS
Without RT	Shorter 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 EuroPMC
==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 EuroPMC
==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 longer DFS
Concurrent	Might have shorter 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==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	Lower pCR rate
Lapatinib vs. Trastuzumab 	Seems not superior
Lapatinib & Trastuzumab vs. Trastuzumab	Higher 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==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 longer EFS
No trastuzumab 	Seems to have shorter 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 EuroPMC
## 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 EuroPMC
==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 EuroPMC
==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 longer MFS
RT first 	Seems to have shorter 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 EuroPMC
==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 shorter RFS
Experimental	Seems to have longer 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 EuroPMC
==SONIA==
===Arm 1===
*First-line Abemaciclib & Anastrozole or Abemaciclib & Letrozole or Anastrozole & Palbociclib or Anastrozole & Ribociclib or Letrozole & Palbociclib or Letrozole & Ribociclib, then second-line Fulvestrant
===Arm 2===
*First-line Anastrozole or Letrozole, then second-line Abemaciclib & Fulvestrant or Fulvestrant & Palbociclib or Fulvestrant & Ribociclib
===Comparative efficacy===
Design 	Efficacy
First-line CDK4/6i 	Might have longer PFS-2 (primary endpoint)Median PFS-2: 31 vs 26.8 mo(sHR 0.87, 95% CI 0.74-1.03)
Second-line CDK4/6i	Might have shorter PFS-2 (primary endpoint)Median PFS-2: 26.8 vs 31 mo(sHR 1.15, 95% CI 0.97-1.35)
===References===
#SONIA: Sonke GS, van Ommen-Nijhof A, Wortelboer N, van der Noort V, Swinkels ACP, Blommestein HM, Guerrero Paez C, Mol L, Beeker A, Beelen K, Hamming LC, Heijns JB, Honkoop AH, de Jong PC, van Rossum-Schornagel QC, van Schaik-van de Mheen C, Tol J, Tromp-van Driel CS, Vrijaldenhoven S, van Leeuwen-Stok AE, Konings IR, Jager A; SONIA Study Consortium. Early versus deferred use of CDK4/6 inhibitors in advanced breast cancer. Nature. 2024 Dec;636(8042):474-480. Epub 2024 Nov 27. link to original article EuroPMC NCT03425838
==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 shorter OS
With chemotherapy	Might have longer OS
====Comparison 2====
Timing 	Efficacy
Concurrent (CAFT) 	Might have shorter DFS
Sequential (CAF-T)	Might have longer 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 EuroPMC
==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 EuroPMC
=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 shorter RFS
With EPO	Might have longer 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 EuroPMC
=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 EuroPMC
==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 EuroPMC
=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 shorter OS
CHOP x 3, then RT	Seems to have longer 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 EuroPMC
=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 shorter OS1
Chemoradiotherapy	Seems to have longer 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 EuroPMC
## 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 link to PMC article EuroPMC
=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 	Shorter PFS 	Less toxicity
Obinutuzumab-chemotherapy	Longer PFS (primary endpoint)PFS36: 80% vs 73%(HR 0.66, 95% CI 0.51-0.85)	More 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 EuroPMC
=Gastroesophageal cancer=
==POET==
===Arm 1===
*PLF x 15 wk, then surgery
===Arm 2===
*PLF x 12 wk, then EP & RT, then surgery
===Comparative efficacy===
Regimen 	Efficacy
Neoadjuvant chemotherapy only 	Might have shorter OS
Neoadjuvant chemotherapy and chemoradiotherapy	Might have longer 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 EuroPMC
==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 EuroPMC
=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 	Shorter PFS
Bevacizumab-containing arm	Longer 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 EuroPMC
==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 	Shorter OS
Temozolomide-containing arm	Longer 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 EuroPMC
==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 shorter PFS, the effect size did not reach the prespecified improvement target.
Regimen 	Efficacy
Temozolomide alone 	Shorter PFS
Bevacizumab-containing arm	Longer 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 EuroPMC
=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 EuroPMC
==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. 	 	Shorter LFS 	Seems to have longer LFS
Arm 2 vs. 	Longer LFS 	 	Seems to have longer LFS
Arm 3 vs. 	Seems to have shorter LFS	Seems to have shorter 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 EuroPMC
## 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 EuroPMC
=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	Longer OS
STNI 	Shorter 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 dosing details in supplement have been reviewed by our editors EuroPMC
==EORTC-GELA H8-U==
===Arm 1===
*MOPP-ABV x 4, then IFRT
===Arm 2===
*MOPP-ABV x 4, then STNI
===Arm 3 (control)===
*MOPP-ABV x 6, then IFRT
===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 dosing details in supplement have been reviewed by our editors EuroPMC
==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 EuroPMC
## 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 EuroPMC
==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 EuroPMC 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 longer OS
ABVD x 2, then STNI	Seems to have shorter 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 EuroPMC
## 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 EuroPMC
=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 shorter TTTF
Cytarabine-based	Seems to have longer 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 EuroPMC
##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 EuroPMC
=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 	Shorter PFS
Thalidomide-based	Longer 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 EuroPMC
## 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 EuroPMC
=Non-small cell lung cancer=
==ECOG 3598==
===Arm 1 (Control)===
*PC induction, then CP & RT
===Arm 2, with thalidomide (Experimental)===
*TPC, then CP, 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 EuroPMC
==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 dosing details in manuscript have been reviewed by our editors EuroPMC
==RTOG 9410==
===Arm 1, sequential (control)===
*Cisplatin & Vinblastine, then RT
===Arm 2, concurrent (experimental)===
*EP & RT
===Arm 3, concurrent (experimental)===
*Cisplatin, Vinblastine, RT
===Comparative efficacy===
Schedule 	Efficacy
Concurrent	Seems to have longer OS
Sequential	Seems to have shorter 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 EuroPMC
=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 shorter OS
Experimental	Seems to have longer 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 EuroPMC
=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 longer OS
With Erlotinib	Might have shorter 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 EuroPMC
=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 	Lower pCR rate
Experimental	Higher 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 EuroPMC 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 	Lower DRTF36 (primary endpoint)DRTF36: 23.7% vs 30.4%(HR 0.75, 95% CI 0.60-0.95)
Chemo-RT, then TME, +/- adjuvant chemo	Higher DRTF36 (primary endpoint)DRTF36: 30.4% vs 23.7%(HR 1.33, 95% CI 1.05-1.67)
===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 EuroPMC
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