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	Alaina J. Brown, MD, MPH Vanderbilt University Nashville, TN, USA LinkedIn

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35 regimens on this page 55 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ESMO

2023: Koppikar et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer PubMed
2022: Oaknin et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2013: Colombo et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Plataniotis & Castiglione. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Baekelandt & Castiglione. Endometrial carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed

2016: Colombo et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up PubMed

NCCN

NCCN Guidelines - Uterine Neoplasms
- 2023: Abu-Rustum et al. Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2018: Koh et al. Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2015: Koh et al. Uterine Sarcoma, Version 1.2016: Featured Updates to the NCCN Guidelines. PubMed
- 2014: Koh et al. Uterine neoplasms, version 1.2014. PubMed
- 2009: Greer et al. Uterine Neoplasms. Clinical Practice Guidelines in Oncology. PubMed

Adjuvant therapy

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 5/175 x 4

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
de Boer et al. 2018 (PORTEC-3)	2006-2013	Phase 3 (E-esc)	See link	See link

Preceding treatment

Surgery, then adjuvant Cisplatin & RT

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 4 cycles

Regimen variant #2, 6/175 x 6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Matei et al. 2019 (GOG 258)	2009-2014	Phase 3 (C)	Cisplatin & RT, then CP x 4	Did not meet primary endpoint of RFS

Preceding treatment

Hysterectomy and bilateral salpingo-oophorectomy, within 8 weeks

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 6 cycles

References

PORTEC-3: 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 NCT00411138
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 contains dosing details in manuscript link to PMC article PubMed
GOG 258: Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, Moxley KM, Kim YM, Powell MA, O'Malley DM, Spirtos NM, Small W Jr, Tewari KS, Richards WE, Nakayama J, Matulonis UA, Huang HQ, Miller DS. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med. 2019 Jun 13;380(24):2317-2326. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00942357
JGOG2043: Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N; Japanese Gynecologic Oncology Group. Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. Epub 2019 Mar 21. link to original article contains dosing details in manuscript link to PMC article PubMed UMIN000000522
KEYNOTE-B21: NCT04634877

Cisplatin & Doxorubicin

CD: Cisplatin & Doxorubicin
AP: Adriamycin (Doxorubicin) & Platinol (Cisplatin)

Regimen variant #1, 50/45, capped BSA

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Homesley et al. 2008 (GOG 184)	2000-2004	Phase 3 (C)	CDP	Did not meet primary endpoint of RFS

Note: Treatment was to start within 8 weeks of completion of RT.

Preceding treatment

Surgery, then adjuvant RT

Chemotherapy

Cisplatin (Platinol) 50 mg/m² (maximum dose of 100 mg) IV once on day 1, given second
Doxorubicin (Adriamycin) 45 mg/m² (maximum dose of 90 mg) IV once on day 1, given first

Supportive therapy

G-CSF, ONE of the following:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC increases to 10,000/μL
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
Dexamethasone (Decadron) 10 mg IV once on day 1, prior to chemotherapy
5-HT3 antagonist

21-day cycle for 6 cycles

Regimen variant #2, 50/60 x 6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Nomura et al. 2019 (JGOG2043)	2006-2011	Phase 3 (C)	1. Carboplatin & Paclitaxel 2. Cisplatin & Docetaxel	Did not meet primary endpoint of PFS

Preceding treatment

Surgery

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1, given second
Doxorubicin (Adriamycin) 60 mg/m² IV once on day 1, given first

21-day cycle for 6 cycles

Regimen variant #3, 50/60 x 8

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Randall et al. 2006 (GOG 122)	1992-2000	Phase 3 (E-switch-ooc)	Whole abdominal irradiation	Superior OS (secondary endpoint) OS60: 55% vs 42% (aHR 0.68, 95% CI 0.52-0.89)

Preceding treatment

Surgery, with optimal debulking

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 7: 60 mg/m² IV once on day 1

Supportive therapy

Normal saline at 500 mL/H for 2 hours prior to and after cisplatin

21-day cycle for 8 cycles

References

GOG 122: Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006 Jan 1;24(1):36-44. Epub 2005 Dec 5. link to original article contains dosing details in manuscript PubMed
GOG 184: Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009 Mar;112(3):543-52. Epub 2008 Dec 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00006011
1. Update: Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT, DeGeest K, Lee RB, Miller DS. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): a randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecol Oncol. 2019 Jul;154(1):13-21. Epub 2019 Apr 30. link to original article link to PMC article PubMed
JGOG2043: Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N; Japanese Gynecologic Oncology Group. Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. Epub 2019 Mar 21. link to original article contains dosing details in manuscript link to PMC article PubMed UMIN000000522

Cisplatin & Ifosfamide

CIM: Cisplatin, Ifosfamide, Mesna

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Wolfson et al. 2007 (GOG 150)	1993-2005	Phase 3 (E-switch-ooc)	Whole abdominal irradiation	Might have superior OS¹ (co-primary endpoint) Median OS: 48 vs 24 mo (HR 0.71, 95% CI 0.48-1.05)

¹Median OS is not reported in the paper and is estimated from the K-M curve.

Preceding treatment

Surgery

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 4, given first, at an infusion rate of approximately 1 mg/min
Ifosfamide (Ifex) 1500 mg/m² IV over 60 minutes once per day on days 1 to 4, given second, with mesna

Supportive therapy

Mesna (Mesnex) 120 mg/m² IV over 15 minutes once on day 1, then 1500 mg/m²/day IV continuous infusion over 96 hours, given second, with ifosfamide
Suggested hydration: 1 liter of NS or 1/2 NS over several hours once per day on days 1 to 4, prior to chemotherapy

21-day cycle for 3 cycles

References

GOG 150: Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, Cohn DE, Ioffe OB. A Gynecologic Oncology Group randomized phase III trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177-85. Epub 2007 Sep 5. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00002546

Cisplatin & RT

Cisplatin & RT: Cisplatin & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
de Boer et al. 2018 (PORTEC-3)	2006-2013	Phase 3 (E-esc)	See link	See link

Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks; reported efficacy is based on the 2019 update.

Preceding treatment

Surgery

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1 & 22

Radiotherapy

External beam radiotherapy to the pelvis, 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36, 37 (27 fractions; total dose: 4860 cGy)

37-day course

Subsequent treatment

Adjuvant Carboplatin & Paclitaxel x 4

References

PORTEC-3: 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 contains dosing details in manuscript link to PMC article PubMed NCT00411138
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 contains dosing details in manuscript link to PMC article PubMed
Lunchbox: Barlin JN, Mahar B, Ata A, Cormier B, Michelin D, Salani R, Backes F, Levinson K, Cantrell LA, Weinberg L, Wagreich A, Savage D, Gasson C, Denniston K, Martin J, McElrath T, Timmins PF. Lunchbox trial: A randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel versus sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial carcinoma. Gynecol Oncol. 2024 Jan;180:63-69. Epub 2023 Dec 5. link to original article PubMed

Radiation therapy

RT: Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Keys et al. 2004 (GOG 99)	1987-1995	Phase 3 (E-esc)	Observation	Superior RFS
Maggi et al. 2006	1990-1997	Phase 3 (C)	CAP	Did not meet co-primary endpoints of PFS/OS
Susumu et al. 2007 (JGOG 2033)	1994-2000	Phase 3 (C)	CAP	Did not meet primary endpoint of OS60
Homesley et al. 2008 (GOG 184)	2000-2004	Non-randomized part of phase 3 RCT
de Boer et al. 2018 (PORTEC-3)	2006-2013	Phase 3 (C)	Cisplatin & RT, then Carboplatin & Paclitaxel	Seems to have inferior OS¹
Randall et al. 2019 (GOG 249)	2009-2013	Phase 3 (C)	Vaginal cuff brachytherapy, then Carboplatin & Paclitaxel	Did not meet primary endpoint of RFS

¹Reported efficacy for PORTEC-3 is based on the 2019 update.
Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks.

Preceding treatment

Surgery

Radiotherapy

External beam radiotherapy to the pelvis, 4000 to 5000 cGy
- If cervical involvement, brachytherapy boost

One course

Subsequent treatment

GOG 184: Adjuvant CD x 6 versus CDP x 6

References

GOG 99: Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG; Gynecologic Oncology Group. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Mar;92(3):744-51. Erratum in: Gynecol Oncol. 2004 Jul;94(1):241-2. link to original article PubMed
Maggi R, Lissoni A, Spina F, Melpignano M, Zola P, Favalli G, Colombo A, Fossati R. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer. 2006 Aug 7;95(3):266-71. Epub 2006 Jul 25. link to original article link to PMC article PubMed
JGOG 2033: Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R; Japanese Gynecologic Oncology Group. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008 Jan;108(1):226-33. Epub 2007 Nov 9. link to original article PubMed
GOG 184: Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009 Mar;112(3):543-52. Epub 2008 Dec 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00006011
1. Update: Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT, DeGeest K, Lee RB, Miller DS. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): a randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecol Oncol. 2019 Jul;154(1):13-21. Epub 2019 Apr 30. link to original article link to PMC article PubMed
PORTEC-3: 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 NCT00411138
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 link to PMC article PubMed
GOG 249: Randall ME, Filiaci V, McMeekin DS, von Gruenigen V, Huang H, Yashar CM, Mannel RS, Kim JW, Salani R, DiSilvestro PA, Burke JJ, Rutherford T, Spirtos NM, Terada K, Anderson PR, Brewster WR, Small W, Aghajanian CA, Miller DS. Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. J Clin Oncol. 2019 Jul 20;37(21):1810-1818. Epub 2019 Apr 17. link to original article link to PMC article PubMed NCT00807768

Whole abdominal radiation (WAI)

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Randall et al. 2006 (GOG 122)	1992-2000	Phase 3 (E-switch-ooc)	Cisplatin & Doxorubicin	Inferior OS (secondary endpoint)
Wolfson et al. 2007 (GOG 150)	1993-2005	Phase 3 (C)	CIM	Might have inferior OS

Not commonly used but was a comparator arm; here for reference purposes only.

Radiotherapy

External beam radiotherapy

References

GOG 122: Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006 Jan 1;24(1):36-44. Epub 2005 Dec 5. link to original article contains dosing details in manuscript PubMed
GOG 150: Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, Cohn DE, Ioffe OB. A Gynecologic Oncology Group randomized phase III trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177-85. Epub 2007 Sep 5. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00002546

Non-endocrine therapy for advanced, recurrent, or metastatic disease

Bevacizumab monotherapy

Regimen

Study	Dates of enrollment	Evidence
Aghajanian et al. 2011 (GOG-0229E)	2006-2007	Phase 2

Targeted therapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycles

References

GOG-0229E: Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK; Gynecologic Oncology Group. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. Epub 2011 May 2. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00301964

Carboplatin monotherapy

Regimen variant #1, 300 mg/m²

Study	Dates of enrollment	Evidence	Efficacy
van Wijk et al. 2003	1985-10 to 1988-08	Phase 2	ORR: 13% (95% CI 6-25%)

Note: This dosing is intended for patients previously treated with chemotherapy.

Chemotherapy

Carboplatin (Paraplatin) 300 mg/m² IV over 30 minutes once on day 1

28-day cycles

Regimen variant #2, 400 mg/m²

Study	Dates of enrollment	Evidence	Efficacy
van Wijk et al. 2003	1985-10 to 1988-08	Phase 2	ORR: 13% (95% CI 6-25%)

Chemotherapy

Carboplatin (Paraplatin) 400 mg/m² IV over 30 minutes once on day 1

28-day cycles

References

van Wijk FH, Lhommé C, Bolis G, Scotto di Palumbo V, Tumolo S, Nooij M, Freire de Oliveira C, Vermorken JB; EORTC Gynaecological Cancer Group. Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma: a trial of the EORTC Gynaecological Cancer Group. Eur J Cancer. 2003 Jan;39(1):78-85. link to original article contains dosing details in manuscript PubMed

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 5/175 x 6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pectasides et al. 2008	2004-01 to 2007-09	Phase 2
Mirza et al. 2023 (RUBY)	2019-2022	Phase 3 (C)	CP & Dostarlimab	Inferior OS
Eskander et al. 2023 (NRG GY018)	2019-07 to 2022-12	Phase 3 (C)	CP & Pembrolizumab	Inferior PFS
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (C)	1. CP & Durvalumab 2. CP, Olaparib, Durvalumab	Inferior PFS

Note: this is the lower limit of cycles in Pectasides et al. 2008.

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 6 cycles

Regimen variant #2, 5/175 x 9

Study	Dates of enrollment	Evidence
Pectasides et al. 2008	2004-01 to 2007-09	Phase 2

Note: this is the upper limit of cycles in Pectasides et al. 2008.

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 9 cycles

Regimen variant #3, 5/175, indefinite

Study	Dates of enrollment	Evidence
Hoskins et al. 2001	1995-1998	Phase 2
Sorbe et al. 2007	2000-2004	Phase 2

Note: this is the lower limit of carboplatin dosing allowed in Hoskins et al. 2001.

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycles

Regimen variant #4, 6/175 x 6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (C)	1. CP & Durvalumab 2. CP, Olaparib, Durvalumab	Inferior PFS

Note: this is the upper limit of carboplatin dosing in DUO-E.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 6 cycles

Regimen variant #5, 6/175 x 7

ESMO-preferred (I-A, 2016)

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Miller et al. 2020 (GOG0209)	2003-2009	Phase 3 (E-de-esc)	TAP	Non-inferior OS (primary endpoint) Median OS: 37 vs 41 mo (HR 1.002, 90% CI 0.9-1.12)

Note: ESMO recommends 6 cycles, whereas the cited RCT uses 7 cycles.

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 7 cycles

Regimen variant #6, 6/175 x 6-10

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Powell et al. 2022 (GOG-0261)	2009-2014	Phase 3 (E-switch-ic)	Ifosfamide & Paclitaxel	Non-inferior OS (primary endpoint) Median OS: 37 vs 29 mo (HR 0.87, 90% CI 0.70-1.075)

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 6 to 10 cycles

Regimen variant #7, 7/175

Study	Dates of enrollment	Evidence
Hoskins et al. 2001	1995-1998	Phase 2

Note: this is the upper limit of carboplatin dosing allowed in Hoskins et al. 2001.

Chemotherapy

Carboplatin (Paraplatin) AUC 7 IV once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

21-day cycles

References

Hoskins PJ, Swenerton KD, Pike JA, Wong F, Lim P, Acquino-Parsons C, Lee N. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol. 2001 Oct 15;19(20):4048-53. link to original article contains dosing details in manuscript PubMed
Sorbe B, Andersson H, Boman K, Rosenberg P, Kalling M. Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. Int J Gynecol Cancer. 2008 Jul-Aug;18(4):803-8. Epub 2007 Oct 18. link to original article contains dosing details in manuscript PubMed
Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, Psyrri A, Gaglia A, Kassanos D, Gouveris P, Panayiotidis J, Fountzilas G, Economopoulos T. Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol. 2008 May;109(2):250-4. Epub 2008 Mar 4. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org
Retrospective: Shechter-Maor G, Bruchim I, Ben-Harim Z, Altaras M, Fishman A. Combined chemotherapy regimen of carboplatin and paclitaxel as adjuvant treatment for papillary serous and clear cell endometrial cancer. Int J Gynecol Cancer. 2009 May;19(4):662-4. link to original article PubMed
GOG0209: Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, DiSilvestro P, Pearl ML, Argenta PA, Powell MA, Zweizig SL, Warshal DP, Hanjani P, Carney ME, Huang H, Cella D, Zaino R, Fleming GF. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol. 2020 Nov 20;38(33):3841-3850. Epub 2020 Sep 29. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00063999
GOG-0261: Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. Epub 2022 Jan 10. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00954174
RUBY: Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. Epub 2023 Mar 27. link to original article PubMed NCT03981796
NRG GY018: Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. Epub 2023 Mar 27. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03914612
DUO-E: Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT04269200

Carboplatin & Paclitaxel (CP) & Dostarlimab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Mirza et al. 2023 (RUBY)	2019-2022	Phase 3 (E-RT-esc)	CP	Superior OS (co-primary endpoint) OS24: 71.3% vs 56% (HR 0.64, 95% CI 0.46-0.87)

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV once on day 1

Immunotherapy

Dostarlimab (Jemperli) as follows:
- Cycles 1 to 6: 500 mg IV once on day 1
- Cycles 7 to 32: 1000 mg IV once on day 1

21-day cycle for 6 cycles, then 42-day cycle for up to 26 cycles (3 years)

References

RUBY: Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. Epub 2023 Mar 27. link to original article PubMed NCT03981796

Carboplatin & Paclitaxel (CP) & Durvalumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-RT-esc)	1. CP	Superior PFS (primary endpoint) Median PFS: 10.2 vs 9.6 mo (HR 0.71, 95% CI 0.57-0.89) Superior dMMR subgroup PFS¹ (secondary endpoint) Median PFS: NYR vs 7 mo (HR 0.42, 95% CI 0.22-0.80)
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-RT-esc)	2. CP, Olaparib, Durvalumab	Not formally compared

¹PFS analysis of the dMMR subgroup was prespecified; FDA approval is for this subgroup.

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 to 6 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV once on day 1

Immunotherapy

Durvalumab (Imfinzi) as follows:
- Cycles 1 to 6: 1120 mg IV once on day 1
- Cycle 7 onwards: 1500 mg IV once on day 1

21-day cycle for 6 cycles, then 28-day cycles

References

DUO-E: Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT04269200

Carboplatin & Paclitaxel (CP), Olaparib, Durvalumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-esc)	1. CP	Superior PFS (primary endpoint) Median PFS: 15.1 vs 9.6 mo (HR 0.55, 95% CI 0.43-0.69)
Westin et al. 2023 (DUO-E)	2020-06-02 to 2022-04-20	Phase 3 (E-esc)	2. CP & Durvalumab\|CP & Durvalumab	Not formally compared

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 to 6 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV once on day 1

Immunotherapy

Durvalumab (Imfinzi) as follows:
- Cycles 1 to 6: 1120 mg IV once on day 1
- Cycle 7 onwards: 1500 mg IV once on day 1

Targeted therapy

Olaparib (Lynparza) as follows:
- Cycle 7 onwards: 300 mg PO twice per day on days 1 to 28

21-day cycle for 6 cycles, then 28-day cycles

References

DUO-E: Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. link to original article contains dosing details in manuscript link to PMC article PubMed NCT04269200

Carboplatin & Paclitaxel (CP) & Pembrolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Eskander et al. 2023 (NRG GY018)	2019-07 to 2022-12	Phase 3 (E-RT-esc)	CP	Superior PFS¹ (co-primary endpoint) PFS12: 74% vs 38% (HR 0.30, 95% CI 0.19-0.48) Superior PFS² (co-primary endpoint) Median PFS: 13.1 vs 8.7 mo (HR 0.54, 95% CI 0.41-0.71)

¹Reported efficacy is for the dMMR cohort.
²Reported efficacy is for the pMMR cohort.

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV over 30 to 60 minutes once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV over 3 hours once on day 1

Immunotherapy

Pembrolizumab (Keytruda) as follows:
- Cycles 1 to 6: 200 mg IV over 30 minutes once on day 1
- Cycles 7 to 20: 400 mg IV over 30 minutes once on day 1

21-day cycle for 6 cycles, then 42-day cycle for 14 cycles

References

NRG GY018: Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. Epub 2023 Mar 27. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03914612

Carboplatin & Paclitaxel (CP) & Trastuzumab

CP+T: Carboplatin, Paclitaxel, Trastuzumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fader et al. 2018	2011-2017	Randomized Phase 2 (E-esc)	CP	Superior PFS¹ (primary endpoint) Median PFS: 12.9 vs 8 mo (HR 0.46, 90% CI 0.28-0.76)

¹Reported efficacy is based on the 2020 update.

Biomarker eligibility criteria

HER2 overexpression

Chemotherapy

Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m² IV over 3 hours once on day 1

Targeted therapy

Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol. 2018 Jul 10;36(20):2044-2051. Epub 2018 Mar 27. link to original article contains dosing details in manuscript PubMed NCT01367002
1. Update: Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res. 2020 Aug 1;26(15):3928-3935. Epub 2020 Jun 29. link to original article link to PMC article PubMed

Carboplatin & Pegylated liposomal doxorubicin

Regimen

Study	Dates of enrollment	Evidence
Pignata et al. 2007 (END-1)	2002-2005	Phase 2

Note: All patients received 3 cycles of therapy. If there was no unacceptable toxicity, patients with stable or responsive disease received an additional 3 cycles.

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given first
Pegylated liposomal doxorubicin (Doxil) 40 mg/m² IV over 60 minutes once on day 1, given second

28-day cycle for 3 to 6 cycles

Dose and schedule modifications

G-CSF were not recommended for prophylaxis, but were allowed for grade 4 neutropenia

References

END-1: Pignata S, Scambia G, Pisano C, Breda E, Di Maio M, Greggi S, Ferrandina G, Lorusso D, Zagonel V, Febbraro A, Riva N, De Rosa V, Gallo C, Perrone F; Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies Group. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer. 2007 Jun 4;96(11):1639-43. Epub 2007 May 8. link to original article contains dosing details in manuscript link to PMC article PubMed

Cisplatin & Doxorubicin

AP: Adriamycin (Doxorubicin) & Platinol (Cisplatin)

Regimen variant #1, 50/45

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fleming et al. 2004a (GOG 177)	1998-2000	Phase 3 (C)	Cisplatin, Doxorubicin, Paclitaxel	Seems to have inferior OS

Note: body surface area was capped at 2 m². This dosage was for patients with previous pelvic radiation or who were greater than 65 years old.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² (maximum dose of 100 mg) IV over 60 minutes once on day 1, given second
Doxorubicin (Adriamycin) 45 mg/m² (maximum dose of 90 mg) IV once on day 1, given first

21-day cycle for 7 cycles

Regimen variant #2, 50/60, capped BSA

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fleming et al. 2004a (GOG 177)	1998-2000	Phase 3 (C)	Cisplatin, Doxorubicin, Paclitaxel	Seems to have inferior OS

Note: body surface area was capped at 2 m².

Chemotherapy

Cisplatin (Platinol) 50 mg/m² (maximum dose of 100 mg) IV over 60 minutes once on day 1, given second
Doxorubicin (Adriamycin) 60 mg/m² (maximum dose of 120 mg) IV once on day 1, given first

21-day cycle for 7 cycles

Regimen variant #3, 50/60, no cap on BSA

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fleming et al. 2004 (GOG 163)	1996-1998	Phase 3 (C)	Doxorubicin & Paclitaxel	Did not meet primary endpoint of ORR
Thigpen et al. 2004 (GOG 107)	NR	Phase 3 (E-esc)	Doxorubicin	Seems to have superior PFS

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 60 mg/m² IV once on day 1

Supportive therapy

Normal saline at 500 mL/H for 2 hours prior to and after cisplatin

21-day cycle for up to 8 cycles

Regimen variant #4, 60/60

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gallion et al. 2003 (GOG 139)	1993-1996	Phase 3 (C)	Cisplatin & Doxorubicin; chronomodulated	Did not meet primary endpoint of ORR

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 60 mg/m² IV once on day 1

21-day cycle for up to 8 cycles

References

GOG 139: Gallion HH, Brunetto VL, Cibull M, Lentz SS, Reid G, Soper JT, Burger RA, Andersen W; Gynecologic Oncology Group. Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Oct 15;21(20):3808-13. link to original article contains dosing details in abstract PubMed
GOG 177: Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. link to original article contains dosing details in manuscript PubMed NCT00003691
GOG 163: Fleming GF, Filiaci VL, Bentley RC, Herzog T, Sorosky J, Vaccarello L, Gallion H. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol. 2004 Aug;15(8):1173-8. link to original article contains dosing details in abstract PubMed
GOG 107: Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Oct 1;22(19):3902-8. link to original article contains dosing details in abstract PubMed

Cisplatin, Doxorubicin, Paclitaxel

TAP: Taxol (Paclitaxel), Adriamycin (Doxorubicin), Platinol (Cisplatin)
CDP: Cisplatin, Doxorubicin, Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fleming et al. 2004 (GOG 177)	1998-2000	Phase 3 (E-esc)	Cisplatin & Doxorubicin	Seems to have superior OS (primary endpoint) Median OS: 15.3 vs 12.3 mo (HR 0.75, 95% CI 0.57-0.99)
Miller et al. 2020 (GOG0209)	2003-2009	Phase 3 (C)	TC	Non-inferior OS

Note: in GOG 177, body surface area was capped at 2 m².

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 60 minutes once on day 1, given second
Doxorubicin (Adriamycin) 45 mg/m² IV once on day 1, given first
Paclitaxel (Taxol) 160 mg/m² IV over 3 hours once on day 2

Supportive therapy

Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 3 to 12

21-day cycle for 7 cycles

References

GOG 177: Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. link to original article contains dosing details in manuscript PubMed NCT00003691
GOG0209: Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, DiSilvestro P, Pearl ML, Argenta PA, Powell MA, Zweizig SL, Warshal DP, Hanjani P, Carney ME, Huang H, Cella D, Zaino R, Fleming GF. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol. 2020 Nov 20;38(33):3841-3850. Epub 2020 Sep 29. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00063999

Cisplatin & Ifosfamide

CIM: Cisplatin, Ifosfamide, Mesna

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sutton et al. 2000 (GOG 108)	1989-1996	Phase 3 (E-esc)	Ifosfamide	Seems to have superior PFS (co-primary endpoint)

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 to 5
Ifosfamide (Ifex) 1500 mg/m² IV once per day on days 1 to 5

Supportive therapy

Mesna (Mesnex)

21-day cycle for 8 cycles

References

GOG 108: Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol. 2000 Nov;79(2):147-53. link to original article contains dosing details in abstract PubMed

Cisplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence
Dimopoulos et al. 2000	1995-06 to 1997-05	Phase 2

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 2 hours once on day 1, given second
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1, given first

Supportive therapy

Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
Diphenhydramine (Benadryl) 25 mg IV once on day 1; 30 minutes prior to paclitaxel
Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
900 mL normal saline mixed with 100 mL mannitol given over 1 hour prior to cisplatin
2 liters NS with potassium & magnesium after cisplatin
"Appropriate antiemetics"
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 5 and continuing until WBC greater than 10,000 x 10⁹/L

21-day cycle for up to 6 cycles

References

Dimopoulos MA, Papadimitriou CA, Georgoulias V, Moulopoulos LA, Aravantinos G, Gika D, Karpathios S, Stamatelopoulos S. Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol Oncol. 2000 Jul;78(1):52-7. link to original article contains dosing details in manuscript PubMed

Dactinomycin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Moore et al. 1999	1996	Phase 2

Chemotherapy

Dactinomycin (Cosmegen) 2 mg/m² IV over 15 minutes once on day 1

28-day cycles

References

Moore DH, Blessing JA, Dunton C, Buller RE, Reid GC; Gynecologic Oncology Group. Dactinomycin in the treatment of recurrent or persistent endometrial carcinoma: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 1999 Dec;75(3):473-5. link to original article contains dosing details in manuscript PubMed

Dostarlimab monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence
Oaknin et al. 2020 (GARNET_endometrial)	2017-2019	Phase 1, >20 pts in this cohort (RT)

Immunotherapy

Dostarlimab (Jemperli) as follows:
- Cycles 1 to 4: 500 mg IV over 30 minutes once on day 1
- Cycle 5 onwards: 1000 mg IV over 30 minutes once on day 1

21-day cycle for 4 cycles, then 42-day cycles

References

GARNET_endometrial: Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):1766-1772. Epub 2020 Oct 1. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02715284
1. Update: Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, Sabatier R, O'Malley DM, Samouelian V, Boni V, Duska L, Ghamande S, Ghatage P, Kristeleit R, Leath C III, Guo W, Im E, Zildjian S, Han X, Duan T, Veneris J, Pothuri B. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022 Jan;10(1):e003777. link to original article link to PMC article PubMed
2. PRO analysis: Kristeleit R, Mathews C, Redondo A, Boklage S, Hanlon J, Im E, Brown J. Patient-reported outcomes in the GARNET trial in patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer treated with dostarlimab. Int J Gynecol Cancer. 2022 Aug 16;32(10):1250–7. link to original article link to PMC article PubMed

Doxorubicin monotherapy

Regimen variant #1, 7 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Aapro et al. 2003 (EORTC 55872)	1988-1994	Phase 3 (C)	Cisplatin & Doxorubicin	Might have inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Doxorubicin (Adriamycin) 60 mg/m² IV once on day 1

28-day cycle for up to 7 cycles

Regimen variant #2, 8 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Thigpen et al. 1979	NR	Phase 2
Omura et al. 1983 (GOG 21)	1973-1979	Randomized (C)	Dacarbazine & Doxorubicin	Did not meet primary endpoint of ORR
Muss et al. 1985 (GOG 42)	1979-1982	Phase 3 (C)	Cyclophosphamide & Doxorubicin (AC)	Did not meet efficacy endpoints
Thigpen et al. 1994 (GOG 48)	1979-1985	Randomized (C)	Cyclophosphamide & Doxorubicin (AC)	Did not meet efficacy endpoints
Thigpen et al. 2004 (GOG 107)	NR	Phase 3 (C)	Cisplatin & Doxorubicin	Seems to have inferior PFS
Makker et al. 2022 (KEYNOTE-775)	2018-2020	Phase 3 (C)	Lenvatinib & Pembrolizumab	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Doxorubicin (Adriamycin) 60 mg/m² IV over 60 minutes once on day 1

21-day cycle for up to 8 cycles

References

Thigpen JT, Buchsbaum HJ, Mangan C, Blessing JA; Gynecologic Oncology Group. Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Cancer Treat Rep. 1979 Jan;63(1):21-7. PubMed
GOG 21: Omura GA, Major FJ, Blessing JA, Sedlacek TV, Thigpen JT, Creasman WT, Zaino RJ. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer. 1983 Aug 15;52(4):626-32. link to original article PubMed
GOG 42: Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC Jr, Creasman W, Yordan E. Treatment of recurrent or advanced uterine sarcoma: a randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer. 1985 Apr 15;55(8):1648-53. link to original article PubMed
GOG 48: Thigpen JT, Blessing JA, DiSaia PJ, Yordan E, Carson LF, Evers C. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1994 Jul;12(7):1408-14. link to original article contains dosing details in abstract PubMed
EORTC 55872: Aapro MS, van Wijk FH, Bolis G, Chevallier B, van der Burg ME, Poveda A, Freire de Oliveira C, Tumolo S, Scotto di Palumbo V, Piccart M, Franchi M, Zanaboni F, Lacave AJ, Fontanelli R, Favalli G, Zola P, Guastalla JP, Rosso R, Marth C, Nooij M, Presti M, Scarabelli C, Splinter TA, Ploch E, Beex LV, ten Bokkel Huinink W, Forni M, Melpignano M, Blake P, Kerbrat P, Mendiola C, Cervantes A, Goupil A, Harper PG, Madronal C, Namer M, Scarfone G, Stoot JE, Teodorovic I, Coens C, Vergote I, Vermorken JB; EORTC Gynaecological Cancer Group. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. 2003 Mar;14(3):441-8. Erratum in: Ann Oncol. 2003 May;14(5):811. link to original article contains dosing details in manuscript PubMed
GOG 107: Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Oct 1;22(19):3902-8. link to original article contains dosing details in abstract PubMed
KEYNOTE-775: Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. link to original article contains dosing details in manuscript PubMed NCT03517449
1. Update: Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. link to original article link to PMC article PubMed

Ifosfamide monotherapy

Regimen variant #1, 1200 mg/m² (3 days/cycle)

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Homesley et al. 2007 (GOG 161)	1997-2004	Phase 3 (C)	Ifosfamide & Paclitaxel	Seems to have inferior OS

Note: GOG 161 specifies that PO Mesna (Mesnex) is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references. This dosage is intended for patients with previous radiation.

Chemotherapy

Ifosfamide (Ifex) 1200 mg/m² IV once per day on days 1 to 3

Supportive therapy

Mesna (Mesnex) by the following route-based criteria:
- IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m²)
- PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL

21-day cycle for 8 cycles

Regimen variant #2, 1500 mg/m² (5 days/cycle)

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sutton et al. 2000 (GOG 108)	1989-1996	Phase 3 (C)	CIM	Seems to have inferior PFS

Chemotherapy

Ifosfamide (Ifex) 1500 mg/m² IV once per day on days 1 to 5

Supportive therapy

Mesna (Mesnex) 1500 mg/m² IV once per day on days 1 to 5

21-day cycle for 8 cycles

Regimen variant #3, 1600 mg/m² (3 days/cycle)

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Homesley et al. 2007 (GOG 161)	1997-2004	Phase 3 (C)	Ifosfamide & Paclitaxel	Seems to have inferior OS

Note: GOG 161 specifies that PO Mesna (Mesnex) is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references.

Chemotherapy

Ifosfamide (Ifex) by the following exposure-based criteria:
- No previous radiation: 1600 mg/m² IV once per day on days 1 to 3
- Previous radiation: 1200 mg/m² IV once per day on days 1 to 3

Supportive therapy

Mesna (Mesnex) by the following route-based criteria:
- IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m²)
- PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL

21-day cycle for 8 cycles

References

GOG 108: Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol. 2000 Nov;79(2):147-53. link to original article contains dosing details in manuscript PubMed
GOG 161: Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Feb 10;25(5):526-31. link to original article contains dosing details in manuscript PubMed NCT00003128

Ifosfamide & Paclitaxel

PI: Paclitaxel & Ifosfamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Homesley et al. 2007 (GOG 161)	1997-2004	Phase 3 (E-esc)	Ifosfamide	Seems to have superior OS (primary endpoint) Median OS: 13.5 vs 8.4 mo (HR 0.69, 95% CI 0.49-0.97)
Powell et al. 2022 (GOG-0261)	2009-2014	Phase 3 (C)	Carboplatin & Paclitaxel	Non-inferior OS

Note: GOG 161 specifies that PO Mesna (Mesnex) is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references. Treatment was given for 8 cycles in GOG 161.

Chemotherapy

Ifosfamide (Ifex) by the following exposure-based criteria:
- No previous radiation: 1600 mg/m² IV once per day on days 1 to 3
- Previous radiation: 1200 mg/m² IV once per day on days 1 to 3
Paclitaxel (Taxol) 135 mg/m² IV over 3 hours once on day 1

Supportive therapy

Per GOG 161:

Mesna (Mesnex) by the following route-based criteria:
- IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m²)
- PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
Dexamethasone (Decadron) 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once on day 1; 30 minutes prior to paclitaxel
One of the following H2 blockers:
- Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
- Ranitidine (Zantac) 50 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycle for 6 to 10 cycles

References

GOG 161: Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Feb 10;25(5):526-31. link to original article contains dosing details in manuscript PubMed NCT00003128
GOG-0261: Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. Epub 2022 Jan 10. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00954174

Lenvatinib & Pembrolizumab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Makker et al. 2019 (KEYNOTE-146)	2015-2017	Phase 2 (RT)
Makker et al. 2022 (KEYNOTE-775)	2018-2020	Phase 3 (E-RT-switch-ooc)	Investigator's choice of: 1a. Doxorubicin 1b. Paclitaxel	Superior OS¹ (co-primary endpoint) Median OS: 18.3 vs 11.4 mo (HR 0.62, 95% CI 0.51-0.75)

¹Reported efficacy is for the overall population.

Targeted therapy

Lenvatinib (Lenvima) 20 mg PO once per day on days 1 to 21

Immunotherapy

Pembrolizumab (Keytruda) as follows:
- Cycle 1 up to 35: 200 mg IV over 30 minutes once on day 1

21-day cycles

References

KEYNOTE-146: Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):711-718. Epub 2019 Mar 25. link to original article contains dosing details in abstract PubMed NCT02501096
1. Update: Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, Messing M, Stepan DE, Dutcus CE, Wu J, Schmidt EV, Orlowski R, Sachdev P, Shumaker R, Casado Herraez A. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol. 2020 Sep 10;38(26):2981-2992. Epub 2020 Mar 13. link to original article link to PMC article PubMed
KEYNOTE-775: Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. link to original article contains dosing details in manuscript PubMed NCT03517449
1. Update: Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. link to original article link to PMC article PubMed

Paclitaxel monotherapy

Regimen variant #1, 80 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Makker et al. 2022 (KEYNOTE-775)	2018-2020	Phase 3 (C)	Lenvatinib & Pembrolizumab	Inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

Regimen variant #2, 175 mg/m²

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lissoni et al. 1996	1993-1995	Phase 2
Lincoln et al. 2003	1994-1996	Phase 2
McMeekin et al. 2015 (IXAMPLE2)	2009-2012	Phase 3 (C)	Ixabepilone	Seems to have superior OS

Note: in Lincoln et al. 2003, this was the dosage for patients with previous pelvic radiation.

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive therapy

Hydrocortisone (Cortef) 250 mg IV once on day 1; 60 minutes prior to paclitaxel
Chlorpheniramine (Chlor-Trimeton) 10 mg IM once on day 1; 60 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to paclitaxel

21-day cycles

Regimen variant #3, 200 mg/m²

Study	Dates of enrollment	Evidence
Lincoln et al. 2003	1994-1996	Phase 2

Chemotherapy

Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1

Supportive therapy

Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 12 and 6 hours prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV or PO once on day 1; 30 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel

21-day cycles

Dose and schedule modifications

Paclitaxel dose can be changed to 135 or 110 mg/m² depending on toxicity

Regimen variant #4, continuous infusion

Study	Evidence
Ball et al. 1996	Phase 2

Chemotherapy

Paclitaxel (Taxol) by the following exposure-based criteria:
- No prior pelvic radiation: 250 mg/m² IV continuous infusion over 24 hours, started on day 1
- Previous pelvic radiation: 200 mg/m² IV continuous infusion over 24 hours, started on day 1

Supportive therapy

Dexamethasone (Decadron) 20 mg IV or PO for 2 doses on day 1; 12 and 6 hours prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV or PO once on day 1; 30 minutes prior to paclitaxel
Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 3, 24 hours after paclitaxel, continued for at least 12 days or until two successive total leukocyte counts are 10,000 or greater, whichever comes last

21-day cycles

Dose and schedule modifications

Paclitaxel dose can be changed to 200, 170, 135, 110 mg/m² depending on toxicity

References

Ball HG, Blessing JA, Lentz SS, Mutch DG; Gynecologic Oncology Group. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. 1996 Aug;62(2):278-81. link to original article contains dosing details in manuscript PubMed
Lissoni A, Zanetta G, Losa G, Gabriele A, Parma G, Mangioni C. Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer. Ann Oncol. 1996 Oct;7(8):861-3. link to original article contains dosing details in manuscript PubMed
Lincoln S, Blessing JA, Lee RB, Rocereto TF; Gynecologic Oncology Group. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Mar;88(3):277-81. link to original article contains dosing details in manuscript PubMed
IXAMPLE2: McMeekin S, Dizon D, Barter J, Scambia G, Manzyuk L, Lisyanskaya A, Oaknin A, Ringuette S, Mukhopadhyay P, Rosenberg J, Vergote I. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. Gynecol Oncol. 2015 Jul;138(1):18-23. Epub 2015 Apr 26. link to original article contains dosing details in abstract PubMed NCT00883116
KEYNOTE-775: Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. link to original article contains dosing details in manuscript PubMed NCT03517449
1. Update: Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. link to original article link to PMC article PubMed

Pembrolizumab monotherapy

Regimen variant #1, bi-weekly

Study	Dates of enrollment	Evidence
Le et al. 2015 (KEYNOTE-016)	2013-09 to 2016-09	Phase 2, fewer than 20 pts of this subtype
Ott et al. 2017b (KEYNOTE-028_endometrial)	NR	Phase 1b

Note: KEYNOTE-016 was an expansion to a CRC-specific trial.

Immunotherapy

Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1

14-day cycle for up to 52 cycles (2 years)

Regimen variant #2, q3wk

Study	Dates of enrollment	Evidence
O'Malley et al. 2022 (KEYNOTE-158_endometrial)	2016-2020	Phase 2 (RT)

Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.

Biomarker eligibility criteria

Cohort K: MSI-H/dMMR endometrial cancer

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-028_endometrial: Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 2017 Aug 1;35(22):2535-2541. Epub 2017 May 10. link to original article contains dosing details in abstract PubMed NCT02054806
KEYNOTE-016: Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. link to original article contains dosing details in abstract link to PMC article PubMed NCT01876511
1. Update: Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. link to original article link to PMC article contains dosing details in supplement PubMed
KEYNOTE-158_endometrial: O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, Miller WH Jr, Safra T, Italiano A, Mileshkin L, Xu L, Jin F, Norwood K, Maio M. Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. J Clin Oncol. 2022 Mar 1;40(7):752-761. Epub 2022 Jan 6. link to original article link to PMC article contains dosing details in abstract PubMed NCT02628067

Temsirolimus monotherapy

Regimen

Study	Dates of enrollment	Evidence
Oza et al. 2011 (NCIC IND.160)	2004-2007	Phase 2

Targeted therapy

Temsirolimus (Torisel) 25 mg IV over 30 minutes once on day 1

7-day cycles

References

NCIC IND.160: Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, Gotlieb WH, Hoskins PJ, Ghatage P, Tonkin KS, Mackay HJ, Mazurka J, Sederias J, Ivy P, Dancey JE, Eisenhauer EA; NCIC Clinical Trials Group. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011 Aug 20;29(24):3278-85. Epub 2011 Jul 25. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00072176

Topotecan monotherapy

Regimen

Study	Dates of enrollment	Evidence
Wadler et al. 2003 (ECOG E3E93)	1995-NR	Phase 2

Chemotherapy

Topotecan (Hycamtin) by the following exposure-based criteria:
- No prior pelvic radiation: 1.5 mg/m² IV once per day on days 1 to 5
- Previous pelvic radiation: 1.2 mg/m² IV once per day on days 1 to 5

21-day cycles

Dose and schedule modifications

Topotecan dosage for patients with previous pelvic radiation can be increased to the 1.5 mg/m² dose in later cycles if there are no toxicities higher than grade 1

References

ECOG E3E93: Wadler S, Levy DE, Lincoln ST, Soori GS, Schink JC, Goldberg G. Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93. J Clin Oncol. 2003 Jun 1;21(11):2110-4. link to original article contains dosing details in manuscript PubMed

Endocrine therapy for advanced, recurrent, or metastatic disease

Anastrozole monotherapy

Regimen

Study	Dates of enrollment	Evidence
Rose et al. 2000	1997-05 to 1998-03	Phase 2

Endocrine therapy

Anastrozole (Arimidex) 1 mg PO once per day

Continued indefinitely

References

Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB; Gynecologic Oncology Group. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000 Aug;78(2):212-6. link to original article contains dosing details in manuscript PubMed

Medroxyprogesterone acetate monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kelley & Baker 1961	1950-1959	Non-randomized
Thigpen et al. 1999	1985-1989	Phase 3 (C)	MPA; high-dose	Did not meet primary endpoint of ORR

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Kelley & Baker 1961 examined a variety of progestins and is included for historic interest.

Endocrine therapy

Medroxyprogesterone acetate (MPA) 200 mg PO once per day

Continued indefinitely

References

Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. link to original article PubMed
Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT; Gynecologic Oncology Group. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999 Jun;17(6):1736-44. link to original article contains dosing details in manuscript PubMed

Medroxyprogesterone acetate & Tamoxifen

Regimen

Study	Dates of enrollment	Evidence
Whitney et al. 2004	1991-06 to 1996-02	Phase 2

Endocrine therapy

Medroxyprogesterone acetate (MPA) 100 mg PO twice per day on days 8 to 14, 22 to 28 (even-numbered weeks)
Tamoxifen (Nolvadex) 20 mg PO twice per day on days 1 to 28

28-day cycles

References

Whitney CW, Brunetto VL, Zaino RJ, Lentz SS, Sorosky J, Armstrong DK, Lee RB; Gynecologic Oncology Group. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):4-9. link to original article contains dosing details in manuscript PubMed

Megestrol monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kelley & Baker 1961	1950-1959	Non-randomized
Pandya et al. 2001 (ECOG E4882)	1982-1984	Randomized Phase 2 (C)	Megestrol & Tamoxifen	Did not meet efficacy endpoints

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Kelley & Baker 1961 examined a variety of progestins and is included for historic interest.

Endocrine therapy

Megestrol (Megace) 80 mg PO twice per day

Continued indefinitely

References

Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. link to original article PubMed
ECOG E4882: Pandya KJ, Yeap BY, Weiner LM, Krook JE, Erban JK, Schinella RA, Davis TE. Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol. 2001 Feb;24(1):43-6. link to original article contains dosing details in manuscript PubMed

Megestrol & Tamoxifen

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pandya et al. 2001 (ECOG E4882)	1982-1984	Randomized Phase 2 (E-switch-ic)	Megestrol	Did not meet primary efficacy endpoints
Fiorica et al. 2004	1994-1995	Phase 2

Endocrine therapy

Megestrol (Megace) as follows:
- Odd cycles: 80 mg PO twice per day on days 1 to 21
Tamoxifen (Nolvadex) as follows:
- Even cycles: 20 mg PO twice per day on days 1 to 21

21-day cycles

References

ECOG E4882: Pandya KJ, Yeap BY, Weiner LM, Krook JE, Erban JK, Schinella RA, Davis TE. Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol. 2001 Feb;24(1):43-6. link to original article contains dosing details in manuscript PubMed
Fiorica JV, Brunetto VL, Hanjani P, Lentz SS, Mannel R, Andersen W; Gynecologic Oncology Group. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):10-4. link to original article contains dosing details in manuscript PubMed

Tamoxifen monotherapy

Regimen

Study	Dates of enrollment	Evidence
Quinn et al. 1989	NR	Phase 2
Thigpen et al. 2001 (GOG-81F)	1987-1991	Phase 2

Endocrine therapy

Tamoxifen (Nolvadex) 20 mg PO twice per day

Continued indefinitely

References

Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. 1989 Jan;32(1):1-3. link to original article PubMed
GOG-81F: Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Jan 15;19(2):364-7. link to original article contains dosing details in manuscript PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|gi}}
+{{#lst:Editorial board transclusions|gyn}}
-<big>Note: the page has systemic regimens for the more general category of RAS wild-type colorectal cancer. Also note that most of the regimens were evaluated on patients tested for KRAS mutations only, and that the definition of wild-type has evolved over time. See individual regimen biomarker eligibility criteria for more details.
+''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Endometrial cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''
-*See the [[Colorectal_cancer|'''main colorectal cancer page''']] for general regimens.
-*See the [[Colon cancer, RAS wild-type|'''RAS wild-type colon cancer page''']] for adjuvant colon cancer regimens.</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 14: / Line 12: @@
 {{TOC limit|limit=3}}
 =Guidelines=
-==[http://www.esmo.org/ ESMO]==
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
-*'''2016:''' [http://annonc.oxfordjournals.org/content/27/8/1386.full.pdf+html ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.] [https://pubmed.ncbi.nlm.nih.gov/27380959 PubMed]
+==[https://www.esmo.org/ ESMO]==
-*'''2013:''' [http://annonc.oxfordjournals.org/content/24/suppl_6/vi73.full.pdf+html Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/23813931 PubMed]
+*'''2023:''' Koppikar et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10024150/ Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with endometrial cancer] [https://pubmed.ncbi.nlm.nih.gov/36696825/ PubMed]
-==[http://www.jsccr.jp/en/index.html Japanese Society for Cancer of the Colon and Rectum]==
+*'''2022:''' Oaknin et al. [https://doi.org/10.1016/j.annonc.2022.05.009 Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/35690222 PubMed]
-*'''2016:''' [https://doi.org/10.1007/s10147-017-1101-6 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer] [https://pubmed.ncbi.nlm.nih.gov/28349281 PubMed]
+**'''2013:''' Colombo et al. [https://doi.org/10.1093/annonc/mdt353 Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/24078661/ PubMed]
-==[https://www.nccn.org/ NCCN]==
+**'''2010:''' Plataniotis & Castiglione. [https://doi.org/10.1093/annonc/mdq245 Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555100/ PubMed]
-*[https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf NCCN Guidelines - Colon Cancer]
+**'''2009:''' Baekelandt & Castiglione. [https://doi.org/10.1093/annonc/mdp120 Endometrial carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454455/ PubMed]
-=Perioperative therapy for oligometastatic disease=
-==FOLFIRI {{#subobject:a051ec|Regimen=1}}==
+*'''2016:''' Colombo et al. [https://doi.org/10.1093/annonc/mdv484 ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/26634381 PubMed]
-FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1473 NCCN Guidelines - Uterine Neoplasms]
+**'''2023:''' Abu-Rustum et al. [https://doi.org/10.6004/Jnccn.2023.0006 Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/36791750/ PubMed]
+**'''2018:''' Koh et al. [https://doi.org/10.6004/Jnccn.2018.0006 Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/29439178/ PubMed]
+**'''2015:''' Koh et al. [https://doi.org/10.6004/Jnccn.2015.0162 Uterine Sarcoma, Version 1.2016: Featured Updates to the NCCN Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/26553763/ PubMed]
+**'''2014:''' Koh et al. [https://doi.org/10.6004/Jnccn.2014.0025 Uterine neoplasms, version 1.2014.] [https://pubmed.ncbi.nlm.nih.gov/24586086/ PubMed]
+**'''2009:''' Greer et al. [https://doi.org/10.6004/Jnccn.2009.0035 Uterine Neoplasms. Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/19460278/ PubMed]
+=Adjuvant therapy=
+==Carboplatin & Paclitaxel (CP) {{#subobject:b9c21f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:49d215|Variant=1}}===
+===Regimen variant #1, 5/175 x 4 {{#subobject:6bc3c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2012.44.8308 Ye et al. 2013 (Fudan 2012-03)]
+|[https://doi.org/10.1016/S1470-2045(18)30079-2 de Boer et al. 2018 (PORTEC-3)]
-|2008-2011 (NR)
+|2006-2013
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Complex_multipart_regimens#PORTEC-3|See link]]
+| style="background-color:#91cf60" |[[Complex_multipart_regimens#PORTEC-3|See link]]
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]], then adjuvant [[#Cisplatin_.26_RT|Cisplatin & RT]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 6/175 x 6 {{#subobject:6bc5c0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6948006/ Matei et al. 2019 (GOG 258)]
+|2009-2014
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#FOLFIRI_.26_Cetuximab|FOLFIRI & Cetuximab]]
+|[[#Cisplatin_.26_RT|Cisplatin & RT]], then [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]] x 4
-| style="background-color:#d73027" |Inferior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 |-
 |}
-''Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Hysterectomy|Hysterectomy]] and [[Surgery#Bilateral_salpingo-oophorectomy|bilateral salpingo-oophorectomy]], within 8 weeks
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 6 cycles'''
-'''14-day cycles until lesions deemed resectable or up to 12 cycles'''
 </div></div>
 ===References===
-#'''Fudan 2012-03:''' Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. [https://doi.org/10.1200/JCO.2012.44.8308 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569301 PubMed] NCT01564810
+# '''PORTEC-3:''' 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] [https://clinicaltrials.gov/study/NCT00411138 NCT00411138]
-==FOLFIRI & Cetuximab {{#subobject:a051ec|Regimen=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. [https://doi.org/10.1016/S1470-2045(19)30395-X link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6722042/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31345626/ PubMed]
-FOLFIRI & Cetuximab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Cetuximab
+# '''GOG 258:''' Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, Moxley KM, Kim YM, Powell MA, O'Malley DM, Spirtos NM, Small W Jr, Tewari KS, Richards WE, Nakayama J, Matulonis UA, Huang HQ, Miller DS. Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med. 2019 Jun 13;380(24):2317-2326. [https://doi.org/10.1056/NEJMoa1813181 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6948006/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31189035/ PubMed] [https://clinicaltrials.gov/study/NCT00942357 NCT00942357]
+# '''JGOG2043:''' Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N; Japanese Gynecologic Oncology Group. Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. Epub 2019 Mar 21. [https://doi.org/10.1001/jamaoncol.2019.0001 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30896757/ PubMed] UMIN000000522
+# '''KEYNOTE-B21:''' [https://clinicaltrials.gov/study/NCT04634877 NCT04634877]
+==Cisplatin & Doxorubicin {{#subobject:4d10f0|Regimen=1}}==
+CD: '''<u>C</u>'''isplatin & '''<u>D</u>'''oxorubicin
+<br>AP: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, weekly cetuximab {{#subobject:8f47f9|Variant=1}}===
+===Regimen variant #1, 50/45, capped BSA {{#subobject:ef532f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2012.44.8308 Ye et al. 2013 (Fudan 2012-03)]
+|[https://doi.org/10.1016/j.ygyno.2008.11.014 Homesley et al. 2008 (GOG 184)]
-|2008-2011 (NR)
+|2000-2004
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#FOLFIRI|FOLFIRI]]
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel_999|CDP]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 30.9 vs 21 mo<br>(HR 0.54, 95% CI 0.33-0.88)
+|style="background-color:#ffffbf"|Did not meet primary endpoint of RFS
 |-
 |}
-''Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.''
+''Note: Treatment was to start within 8 weeks of completion of RT.''
-<div class="toccolours" style="background-color:#fdcdac">
+<div class="toccolours" style="background-color:#cbd5e8">
-====Biomarker eligibility criteria====
+====Preceding treatment====
-*Wild-type KRAS, Wild-type NRAS
+*[[Surgery#Endometrial_cancer_surgery|Surgery]], then adjuvant [[#Radiation_therapy|RT]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV once on day 1, '''given second'''
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 90 mg) IV once on day 1, '''given first'''
+====Supportive therapy====
+*G-CSF, ONE of the following:
+**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 2 to 11, or until ANC increases to 10,000/μL
+**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
+*[[Dexamethasone (Decadron)]] 10 mg IV once on day 1, prior to chemotherapy
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]]
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 50/60 x 6 {{#subobject:5fef3b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567838/ Nomura et al. 2019 (JGOG2043)]
+|2006-2011
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]]<br>2. [[#Cisplatin_.26_Docetaxel_.28DC.29_999|Cisplatin & Docetaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second'''
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1, '''given first'''
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 6 cycles'''
-====Targeted therapy====
-*[[Cetuximab (Erbitux)]] as follows, '''given first''':
-**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once on day 8
-**Cycles 2 up to 12: 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
-'''14-day cycles until lesions deemed resectable or up to 12 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, bi-weekly cetuximab {{#subobject:49d215|Variant=1}}===
+===Regimen variant #3, 50/60 x 8 {{#subobject:5bab3b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2012.44.8308 Ye et al. 2013 (Fudan 2012-03)]
+|[https://doi.org/10.1200/jco.2004.00.7617 Randall et al. 2006 (GOG 122)]
-|2008-2011 (NR)
+|1992-2000
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|[[#FOLFIRI|FOLFIRI]]
+|[[#Whole_abdominal_radiation_.28WAI.29|Whole abdominal irradiation]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 30.9 vs 21 mo<br>(HR 0.54, 95% CI 0.33-0.88)
+|style="background-color:#1a9850"|Superior OS (secondary endpoint)<br>OS60: 55% vs 42%<br>(aHR 0.68, 95% CI 0.52-0.89)
 |-
 |}
-''Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]], with optimal debulking
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] as follows:
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV once on day 1
+**Cycles 1 to 7: 60 mg/m<sup>2</sup> IV once on day 1
-====Targeted therapy====
+====Supportive therapy====
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV once on day 1, '''given first'''
+*Normal saline at 500 mL/H for 2 hours prior to and after cisplatin
-'''14-day cycles until lesions deemed resectable or up to 12 cycles'''
+'''21-day cycle for 8 cycles'''
 </div></div>
 ===References===
-#'''Fudan 2012-03:''' Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. [https://doi.org/10.1200/JCO.2012.44.8308 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569301 PubMed] NCT01564810
+# '''GOG 122:''' Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006 Jan 1;24(1):36-44. Epub 2005 Dec 5. [https://doi.org/10.1200/jco.2004.00.7617 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16330675/ PubMed]
-==mFOLFOX6 {{#subobject:8fcd39|Regimen=1}}==
+# '''GOG 184:''' Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009 Mar;112(3):543-52. Epub 2008 Dec 23. [https://doi.org/10.1016/j.ygyno.2008.11.014 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459781/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19108877/ PubMed] [https://clinicaltrials.gov/study/NCT00006011 NCT00006011]
-mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
+## '''Update:''' Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT, DeGeest K, Lee RB, Miller DS. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): a randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecol Oncol. 2019 Jul;154(1):13-21. Epub 2019 Apr 30. [https://doi.org/10.1016/j.ygyno.2019.03.240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31053405/ PubMed]
+# '''JGOG2043:''' Nomura H, Aoki D, Michimae H, Mizuno M, Nakai H, Arai M, Sasagawa M, Ushijima K, Sugiyama T, Saito M, Tokunaga H, Matoda M, Nakanishi T, Watanabe Y, Takahashi F, Saito T, Yaegashi N; Japanese Gynecologic Oncology Group. Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):833-840. Epub 2019 Mar 21. [https://doi.org/10.1001/jamaoncol.2019.0001 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30896757/ PubMed] UMIN000000522
+==Cisplatin & Ifosfamide {{#subobject:ac4dbb|Regimen=1}}==
+CIM: '''<u>C</u>'''isplatin, '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 400/2800/85, resectable or suboptimally resectable {{#subobject:17252e|Variant=1}}===
+===Regimen {{#subobject:f97ea4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S1470-2045(14)70105-6 Primrose et al. 2014 (New EPOC)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752331 Wolfson et al. 2007 (GOG 150)]
-|2007-2012 (F)
+|1993-2005
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|[[#mFOLFOX6_.26_Cetuximab|mFOLFOX6 & Cetuximab]]
+|[[#Whole_abdominal_radiation_.28WAI.29|Whole abdominal irradiation]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup><br>Median PFS: 22.2 vs 15.5 mo<br>(HR 0.85, 95% CI 0.64-1.15)
+|style="background-color:#d9ef8b"|Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 48 vs 24 mo<br>(HR 0.71, 95% CI 0.48-1.05)
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2020 update.''<br>
+''<sup>1</sup>Median OS is not reported in the paper and is estimated from the K-M curve.''
-''Note: this trial was only open to KRAS wild-type patients with resectable or suboptimally resectable colorectal liver metastases.''
+<div class="toccolours" style="background-color:#cbd5e8">
-<div class="toccolours" style="background-color:#fdcdac">
+====Preceding treatment====
-====Biomarker eligibility criteria====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]]
-*KRAS wild-type
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4, '''given first, at an infusion rate of approximately 1 mg/min'''
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 4, '''given second, with mesna'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+====Supportive therapy====
-'''14-day cycle for 6 cycles, then surgery, then 14-day cycle for 6 cycles'''
+*[[Mesna (Mesnex)]] 120 mg/m<sup>2</sup> IV over 15 minutes once on day 1, then 1500 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, '''given second, with ifosfamide'''
-</div></div><br>
+*Suggested hydration: 1 liter of [[Normal saline|NS]] or 1/2 NS over several hours once per day on days 1 to 4, prior to chemotherapy
+'''21-day cycle for 3 cycles'''
+</div></div>
+===References===
+# '''GOG 150:''' Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, Cohn DE, Ioffe OB. A Gynecologic Oncology Group randomized phase III trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177-85. Epub 2007 Sep 5. [https://doi.org/10.1016/j.ygyno.2007.07.070 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752331/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17822748/ PubMed] [https://clinicaltrials.gov/study/NCT00002546 NCT00002546]
+==Cisplatin & RT {{#subobject:4d8gh0|Regimen=1}}==
+Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 400/2800/85, unresectable {{#subobject:e190fa|Variant=1}}===
+===Regimen {{#subobject:4bfa1d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2012.44.8308 Ye et al. 2013 (Fudan 2012-03)]
+|[https://doi.org/10.1016/S1470-2045(18)30079-2 de Boer et al. 2018 (PORTEC-3)]
-|2008-2011 (NR)
+|2006-2013
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#mFOLFOX6_.26_Cetuximab|mFOLFOX6 & Cetuximab]]
+|[[Complex_multipart_regimens#PORTEC-3|See link]]
-| style="background-color:#d73027" |Inferior OS
+| style="background-color:#91cf60" |[[Complex_multipart_regimens#PORTEC-3|See link]]
 |-
 |}
-''Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.''
+''Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks; reported efficacy is based on the 2019 update.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]]
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 22
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+====Radiotherapy====
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[External beam radiotherapy]] to the pelvis, 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36, 37 (27 fractions; total dose: 4860 cGy)
-'''14-day cycles until lesions deemed resectable or up to 12 cycles'''
+'''37-day course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*Adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] x 4
 </div></div>
 ===References===
-#'''Fudan 2012-03:''' Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. [https://doi.org/10.1200/JCO.2012.44.8308 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569301 PubMed] NCT01564810
+# '''PORTEC-3:''' 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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840256/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29449189/ PubMed] [https://clinicaltrials.gov/study/NCT00411138 NCT00411138]
-#'''New EPOC:''' Primrose J, Falk S, Finch-Jones M, Valle J, O'Reilly D, Siriwardena A, Hornbuckle J, Peterson M, Rees M, Iveson T, Hickish T, Butler R, Stanton L, Dixon E, Little L, Bowers M, Pugh S, Garden OJ, Cunningham D, Maughan T, Bridgewater J. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol. 2014 May;15(6):601-11. Epub 2014 Apr 7. Erratum in: Lancet Oncol. 2014 Jun;15(7):e253. [https://doi.org/10.1016/S1470-2045(14)70105-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24717919 PubMed] ISRCTN22944367
+## '''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] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6722042/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31345626/ PubMed]
-##'''Update:''' Bridgewater JA, Pugh SA, Maishman T, Eminton Z, Mellor J, Whitehead A, Stanton L, Radford M, Corkhill A, Griffiths GO, Falk S, Valle JW, O'Reilly D, Siriwardena AK, Hornbuckle J, Rees M, Iveson TJ, Hickish T, Garden OJ, Cunningham D, Maughan TS, Primrose JN; New EPOC investigators. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Mar;21(3):398-411. Epub 2020 Jan 31. [https://doi.org/10.1016/s1470-2045(19)30798-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7052737/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32014119 PubMed]
+#'''Lunchbox:''' Barlin JN, Mahar B, Ata A, Cormier B, Michelin D, Salani R, Backes F, Levinson K, Cantrell LA, Weinberg L, Wagreich A, Savage D, Gasson C, Denniston K, Martin J, McElrath T, Timmins PF. Lunchbox trial: A randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel versus sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial carcinoma. Gynecol Oncol. 2024 Jan;180:63-69. Epub 2023 Dec 5. [https://doi.org/10.1016/j.ygyno.2023.11.012 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38052110/ PubMed]
-==mFOLFOX6 & Cetuximab {{#subobject:8fcd39|Regimen=1}}==
-mFOLFOX6 & Cetuximab: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Cetuximab
+==Radiation therapy {{#subobject:24a846|Regimen=1}}==
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, weekly cetuximab {{#subobject:dcf5ee|Variant=1}}===
+===Regimen {{#subobject:4bfd6d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2012.44.8308 Ye et al. 2013 (Fudan 2012-03)]
+|[https://doi.org/10.1016/j.ygyno.2003.11.048 Keys et al. 2004 (GOG 99)]
-|2008-2011 (NR)
+|1987-1995
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#mFOLFOX6|mFOLFOX6]]
+|[[Endometrial_cancer_-_null_regimens#Observation|Observation]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 30.9 vs 21 mo<br>(HR 0.54, 95% CI 0.33-0.88)
+| style="background-color:#1a9850" |Superior RFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360651/ Maggi et al. 2006]
+|1990-1997
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#CAP_999|CAP]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS
+|-
+|[https://doi.org/10.1016/j.ygyno.2007.09.029 Susumu et al. 2007 (JGOG 2033)]
+|1994-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#CAP_999|CAP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS60
+|-
+|[https://doi.org/10.1016/j.ygyno.2008.11.014 Homesley et al. 2008 (GOG 184)]
+|2000-2004
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1016/S1470-2045(18)30079-2 de Boer et al. 2018 (PORTEC-3)]
+|2006-2013
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_RT|Cisplatin & RT]], then [[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]]
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6804858/ Randall et al. 2019 (GOG 249)]
+|2009-2013
+|style="background-color:#1a9851"|Phase 3 (C)
+|Vaginal cuff brachytherapy, then [[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 |-
 |}
-''Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.''
+''<sup>1</sup>Reported efficacy for PORTEC-3 is based on the 2019 update.''<br>
-<div class="toccolours" style="background-color:#fdcdac">
+''Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks.''
-====Biomarker eligibility criteria====
+<div class="toccolours" style="background-color:#cbd5e8">
-*Wild-type KRAS, Wild-type NRAS
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Radiotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[External beam radiotherapy]] to the pelvis, 4000 to 5000 cGy
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+**If cervical involvement, brachytherapy boost
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+'''One course'''
-====Targeted therapy====
+</div>
-*[[Cetuximab (Erbitux)]] as follows, '''given first''':
+<div class="toccolours" style="background-color:#cbd5e7">
-**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once on day 8
+====Subsequent treatment====
-**Cycles 2 up to 12: 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*GOG 184: Adjuvant [[#Cisplatin_.26_Doxorubicin|CD]] x 6 versus [[#CDP_999|CDP]] x 6
-'''14-day cycles until lesions deemed resectable or up to 12 cycles'''
+</div></div>
-</div></div><br>
+===References===
+# '''GOG 99:''' Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG; Gynecologic Oncology Group. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Mar;92(3):744-51. Erratum in: Gynecol Oncol. 2004 Jul;94(1):241-2. [https://doi.org/10.1016/j.ygyno.2003.11.048 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14984936/ PubMed]
+# Maggi R, Lissoni A, Spina F, Melpignano M, Zola P, Favalli G, Colombo A, Fossati R. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial. Br J Cancer. 2006 Aug 7;95(3):266-71. Epub 2006 Jul 25. [https://doi.org/10.1038/sj.bjc.6603279 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360651/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16868539/ PubMed]
+# '''JGOG 2033:''' Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R; Japanese Gynecologic Oncology Group. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol. 2008 Jan;108(1):226-33. Epub 2007 Nov 9. [https://doi.org/10.1016/j.ygyno.2007.09.029 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17996926/ PubMed]
+# '''GOG 184:''' Homesley HD, Filiaci V, Gibbons SK, Long HJ, Cella D, Spirtos NM, Morris RT, DeGeest K, Lee R, Montag A. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: A Gynecologic Oncology Group study. Gynecol Oncol. 2009 Mar;112(3):543-52. Epub 2008 Dec 23. [https://doi.org/10.1016/j.ygyno.2008.11.014 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459781/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19108877/ PubMed] [https://clinicaltrials.gov/study/NCT00006011 NCT00006011]
+## '''Update:''' Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT, DeGeest K, Lee RB, Miller DS. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): a randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecol Oncol. 2019 Jul;154(1):13-21. Epub 2019 Apr 30. [https://doi.org/10.1016/j.ygyno.2019.03.240 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31053405/ PubMed]
+# '''PORTEC-3:''' 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] [https://clinicaltrials.gov/study/NCT00411138 NCT00411138]
+## '''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://www.ncbi.nlm.nih.gov/pmc/articles/pmc6722042/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31345626/ PubMed]
+#'''GOG 249:''' Randall ME, Filiaci V, McMeekin DS, von Gruenigen V, Huang H, Yashar CM, Mannel RS, Kim JW, Salani R, DiSilvestro PA, Burke JJ, Rutherford T, Spirtos NM, Terada K, Anderson PR, Brewster WR, Small W, Aghajanian CA, Miller DS. Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. J Clin Oncol. 2019 Jul 20;37(21):1810-1818. Epub 2019 Apr 17. [https://doi.org/10.1200/jco.18.01575 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6804858/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30995174/ PubMed] [https://clinicaltrials.gov/study/NCT00807768 NCT00807768]
+==Whole abdominal radiation (WAI) {{#subobject:37c051|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, bi-weekly cetuximab {{#subobject:e190fa|Variant=1}}===
+===Regimen {{#subobject:1ab715|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2012.44.8308 Ye et al. 2013 (Fudan 2012-03)]
+|[https://doi.org/10.1200/jco.2004.00.7617 Randall et al. 2006 (GOG 122)]
-|2008-2011 (NR)
+|1992-2000
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
-|[[#mFOLFOX6|mFOLFOX6]]
+|[[#Cisplatin_.26_Doxorubicin|Cisplatin & Doxorubicin]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 30.9 vs 21 mo<br>(HR 0.54, 95% CI 0.33-0.88)
+|style="background-color:#d73027"|Inferior OS (secondary endpoint)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752331 Wolfson et al. 2007 (GOG 150)]
+|1993-2005
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Ifosfamide|CIM]]
+|style="background-color:#fee08b"|Might have inferior OS
+|-
+|}
+''Not commonly used but was a comparator arm; here for reference purposes only.''
+====Radiotherapy====
+*[[External beam radiotherapy]]
+</div></div>
+===References===
+# '''GOG 122:''' Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2006 Jan 1;24(1):36-44. Epub 2005 Dec 5. [https://doi.org/10.1200/jco.2004.00.7617 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16330675/ PubMed]
+# '''GOG 150:''' Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, Cohn DE, Ioffe OB. A Gynecologic Oncology Group randomized phase III trial of whole abdominal irradiation (WAI) vs cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-IV carcinosarcoma (CS) of the uterus. Gynecol Oncol. 2007 Nov;107(2):177-85. Epub 2007 Sep 5. [https://doi.org/10.1016/j.ygyno.2007.07.070 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752331/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17822748/ PubMed] [https://clinicaltrials.gov/study/NCT00002546 NCT00002546]
+=Non-endocrine therapy for advanced, recurrent, or metastatic disease=
+==Bevacizumab monotherapy {{#subobject:b29ce2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:8159f4|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107744/ Aghajanian et al. 2011 (GOG-0229E)]
+|2006-2007
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
-''Note: this trial was only open to KRAS wild-type patients with synchronous liver-confined unresectable metastases.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 ====Targeted therapy====
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV once on day 1, '''given first'''
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-'''14-day cycles until lesions deemed resectable or up to 12 cycles'''
+'''21-day cycles'''
 </div></div>
 ===References===
-#'''Fudan 2012-03:''' Ye LC, Liu TS, Ren L, Wei Y, Zhu DX, Zai SY, Ye QH, Yu Y, Xu B, Qin XY, Xu J. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol. 2013 Jun 1;31(16):1931-8. Epub 2013 Apr 8. [https://doi.org/10.1200/JCO.2012.44.8308 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569301 PubMed] NCT01564810
+<!-- Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
-=Advanced or metastatic disease, first-line=
+# '''GOG-0229E:''' Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK; Gynecologic Oncology Group. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2011 Jun 1;29(16):2259-65. Epub 2011 May 2. [https://doi.org/10.1200/jco.2010.32.6397 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107744/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21537039/ PubMed] [https://clinicaltrials.gov/study/NCT00301964 NCT00301964]
-==CapeOx & Panitumumab {{#subobject:22cf7b|Regimen=1}}==
-CapeOx & Panitumumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Panitumumab
+==Carboplatin monotherapy {{#subobject:f9b8ad|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:944ac6|Variant=1}}===
+===Regimen variant #1, 300 mg/m<sup>2</sup> {{#subobject:6a2df1|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 25%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|Dates of enrollment
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+|-
+|[https://doi.org/10.1016/s0959-8049(02)00504-x van Wijk et al. 2003]
+|1985-10 to 1988-08
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#88419d; color:white |ORR: 13% (95% CI 6-25%)
+|-
+|}
+''Note: This dosing is intended for patients previously treated with chemotherapy.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 300 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 400 mg/m<sup>2</sup> {{#subobject:2d401b|Variant=1}}===
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|Dates of enrollment
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://doi.org/10.1007/s12032-018-1160-1 Papaxoinis et al. 2018 (HE 6A/09)]
+|[https://doi.org/10.1016/s0959-8049(02)00504-x van Wijk et al. 2003]
-| style="background-color:#91cf61" |Phase 2
+|1985-10 to 1988-08
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#88419d; color:white |ORR: 13% (95% CI 6-25%)
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+*[[Carboplatin (Paraplatin)]] 400 mg/m<sup>2</sup> IV over 30 minutes once on day 1
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycles'''
-====Targeted therapy====
-*[[Panitumumab (Vectibix)]] 9 mg/kg IV once on day 1
-'''21-day cycles'''
 </div></div>
 ===References===
-#'''HE 6A/09:''' Papaxoinis G, Kotoula V, Giannoulatou E, Koliou GA, Karavasilis V, Lakis S, Koureas A, Bobos M, Chalaralambous E, Daskalaki E, Chatzopoulos K, Tsironis G, Pazarli E, Chrisafi S, Samantas E, Kaklamanos IG, Varthalitis I, Konstantara A, Syrigos KN, Pentheroudakis G, Pectasides D, Fountzilas G. Phase II study of panitumumab combined with capecitabine and oxaliplatin as first-line treatment in metastatic colorectal cancer patients: clinical results including extended tumor genotyping. Med Oncol. 2018 May 31;35(7):101. [https://doi.org/10.1007/s12032-018-1160-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29855806 PubMed] NCT01215539
+# van Wijk FH, Lhommé C, Bolis G, Scotto di Palumbo V, Tumolo S, Nooij M, Freire de Oliveira C, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Gynaecological Cancer Group. Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma: a trial of the EORTC Gynaecological Cancer Group. Eur J Cancer. 2003 Jan;39(1):78-85. [https://doi.org/10.1016/s0959-8049(02)00504-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12504662/ PubMed]
-==FOLFIRI & Bevacizumab {{#subobject:80d6b8|Regimen=1}}==
-FOLFIRI & Bevacizumab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Bevacizumab
+==Carboplatin & Paclitaxel (CP) {{#subobject:b0e21f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:28b67a|Variant=1}}===
+===Regimen variant #1, 5/175 x 6 {{#subobject:7ab5c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S1470-2045(14)70330-4 Heinemann et al. 2014 (FIRE-3)]
+|[https://doi.org/10.1016/j.ygyno.2008.01.028 Pectasides et al. 2008]
-|2007-2012 (C)
+|2004-01 to 2007-09
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|style="background-color:#91cf61"|Phase 2
-|[[#FOLFIRI_.26_Cetuximab_2|FOLFIRI & Cetuximab]]
+| style="background-color:#d3d3d3" |
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1056/nejmoa2216334 Mirza et al. 2023 (RUBY)]
+|2019-2022
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Dostarlimab|CP & Dostarlimab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10351614/ Eskander et al. 2023 (NRG GY018)]
+|2019-07 to 2022-12
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Pembrolizumab|CP & Pembrolizumab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ Westin et al. 2023 (DUO-E)]
+|2020-06-02 to 2022-04-20
+|style="background-color:#1a9851"|Phase 3 (C)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Durvalumab|CP & Durvalumab]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Olaparib.2C_Durvalumab|CP, Olaparib, Durvalumab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+''Note: this is the lower limit of cycles in Pectasides et al. 2008.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 to 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 5/175 x 9 {{#subobject:7ab5c2|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2008.01.028 Pectasides et al. 2008]
+|2004-01 to 2007-09
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+''Note: this is the upper limit of cycles in Pectasides et al. 2008.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with irinotecan'''
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second'''
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1, '''given first, with leucovorin'''
+'''21-day cycle for 9 cycles'''
-====Targeted therapy====
+</div></div><br>
-*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1, '''given second'''
-**In FIRE-3, initial infusion is over 90 minutes, next over 60 minutes, and subsequently over 30 minutes
-'''14-day cycles'''
-</div></div>
-===References===
-#'''FIRE-3:''' Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75. Epub 2014 Jul 31.[https://doi.org/10.1016/S1470-2045(14)70330-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25088940 PubMed] NCT00433927
-==FOLFIRI & Cetuximab {{#subobject:11cf7b|Regimen=1}}==
-FOLFIRI & Cetuximab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Cetuximab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:921ac6|Variant=1}}===
+===Regimen variant #3, 5/175, indefinite {{#subobject:100919|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-|<small>'''FDA-recommended dose'''</small>
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1200/jco.2001.19.20.4048 Hoskins et al. 2001]
+|1995-1998
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1111/j.1525-1438.2007.01094.x Sorbe et al. 2007]
+|2000-2004
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+''Note: this is the lower limit of carboplatin dosing allowed in Hoskins et al. 2001.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, 6/175 x 6 {{#subobject:7gt5c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa0805019 Van Cutsem et al. 2009 (CRYSTAL)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ Westin et al. 2023 (DUO-E)]
-|2004-2005 (C)
+|2020-06-02 to 2022-04-20
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#FOLFIRI|FOLFIRI]]
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Durvalumab|CP & Durvalumab]]<br>2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Olaparib.2C_Durvalumab|CP, Olaparib, Durvalumab]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 23.5 vs 19.5 mo<br>(HR 0.81, 95% CI 0.69-0.94)
+| style="background-color:#d73027" |Inferior PFS
-|-
-|[https://doi.org/10.1016/S1470-2045(14)70330-4 Heinemann et al. 2014 (FIRE-3)]
-|2007-2012 (C)
-| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|[[#FOLFIRI_.26_Bevacizumab|FOLFIRI & Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-''<sup>1</sup>Reported efficacy for CRYSTAL is based on the 2012 pooled update and is only for KRAS wild-type tumors.''
+''Note: this is the upper limit of carboplatin dosing in DUO-E.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*CRYSTAL: none
-*FIRE-3: Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second, 1 hour after completion of cetuximab, with irinotecan'''
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1, '''given second, 1 hour after completion of cetuximab, with leucovorin'''
+'''21-day cycle for 6 cycles'''
-====Targeted therapy====
+</div></div><br>
-*[[Cetuximab (Erbitux)]] as follows, '''given first and completed at least 1 hour before FOLFIRI begins''':
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once on day 8
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
-'''14-day cycles'''
-</div></div>
-===References===
-#'''CRYSTAL:''' Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. [https://doi.org/10.1056/NEJMoa0805019 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19339720 PubMed] NCT00154102
-<!-- ## '''Update: Abstract:''' E. Van Cutsem, I. Lang, G. Folprecht, M. Nowacki, C. Barone, I. Shchepotin, J. Maurel, D. Cunningham, I. Celik, C. Kohne. Cetuximab plus FOLFIRI: Final data from the CRYSTAL study on the association of KRAS and BRAF biomarker status with treatment outcome. 2010 ASCO Annual Meeting abstract 3570. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=54429 link to abstract] -->
-##'''Update:''' Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. [https://doi.org/10.1200/jco.2010.33.5091 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502544 PubMed]
-##'''Pooled update:''' Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. [https://www.ejcancer.com/article/S0959-8049(12)00209-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22446022 PubMed]
-##'''Biomarker analysis:''' Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.59.4812 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25605843 PubMed]
-#'''FIRE-3:''' Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75. Epub 2014 Jul 31. [https://doi.org/10.1016/S1470-2045(14)70330-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25088940 PubMed] NCT00433927
-==FOLFIRI & Cetuximab (L-Leucovorin) {{#subobject:22bf7b|Regimen=1}}==
-FOLFIRI & Cetuximab: L-'''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Cetuximab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8ugac6|Variant=1}}===
+===Regimen variant #5, 6/175 x 7 {{#subobject:a3c4b2|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable" style="color:black; background-color:#42f584"
-|<small>'''FDA-recommended dose'''</small>
+|<small>'''ESMO-preferred (I-A, 2016)'''</small>
 |-
 |}
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa0805019 Van Cutsem et al. 2009 (CRYSTAL)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676887/ Miller et al. 2020 (GOG0209)]
-|2004-2005 (C)
+|2003-2009
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#FOLFIRI|FOLFIRI]]
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel|TAP]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 23.5 vs 19.5 mo<br>(HR 0.81, 95% CI 0.69-0.94)
+| style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>Median OS: 37 vs 41 mo<br>(HR 1.002, 90% CI 0.9-1.12)
-|-
-|[https://doi.org/10.1016/S1470-2045(14)70330-4 Heinemann et al. 2014 (FIRE-3)]
-|2007-2012 (C)
-| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|[[#FOLFIRI_.26_Bevacizumab|FOLFIRI & Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-''<sup>1</sup>Reported efficacy for CRYSTAL is based on the 2012 pooled update and is only for KRAS wild-type tumors.''
+''Note: ESMO recommends 6 cycles, whereas the cited RCT uses 7 cycles.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*CRYSTAL: none
-*FIRE-3: Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second, 1 hour after completion of cetuximab, with irinotecan'''
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1, '''given second'''
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1, '''given second, 1 hour after completion of cetuximab, with L-leucovorin'''
+'''21-day cycle for 7 cycles'''
-====Targeted therapy====
+</div></div><br>
-*[[Cetuximab (Erbitux)]] as follows, '''given first and completed at least 1 hour before FOLFIRI begins''':
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once on day 8
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
-'''14-day cycles'''
-</div></div>
-===References===
-#'''CRYSTAL:''' Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. [https://doi.org/10.1056/NEJMoa0805019 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19339720 PubMed] NCT00154102
-<!-- ## '''Update: Abstract:''' E. Van Cutsem, I. Lang, G. Folprecht, M. Nowacki, C. Barone, I. Shchepotin, J. Maurel, D. Cunningham, I. Celik, C. Kohne. Cetuximab plus FOLFIRI: Final data from the CRYSTAL study on the association of KRAS and BRAF biomarker status with treatment outcome. 2010 ASCO Annual Meeting abstract 3570. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=54429 link to abstract] -->
-##'''Update:''' Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. [https://doi.org/10.1200/jco.2010.33.5091 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502544 PubMed]
-##'''Pooled update:''' Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. [https://www.ejcancer.com/article/S0959-8049(12)00209-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22446022 PubMed]
-##'''Biomarker analysis:''' Van Cutsem E, Lenz HJ, Köhne CH, Heinemann V, Tejpar S, Melezínek I, Beier F, Stroh C, Rougier P, van Krieken JH, Ciardiello F. Fluorouracil, leucovorin, and irinotecan plus cetuximab treatment and RAS mutations in colorectal cancer. J Clin Oncol. 2015 Mar 1;33(7):692-700. Epub 2015 Jan 20. [https://doi.org/10.1200/JCO.2014.59.4812 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25605843 PubMed]
-#'''FIRE-3:''' Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014 Sep;15(10):1065-75. Epub 2014 Jul 31. [https://doi.org/10.1016/S1470-2045(14)70330-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25088940 PubMed] NCT00433927
-==FOLFOX4 {{#subobject:7239a0|Regimen=1}}==
-FOLFOX4: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:ab483a|Variant=1}}===
+===Regimen variant #6, 6/175 x 6-10 {{#subobject:a3jqb2|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2008.20.8397 Bokemeyer et al. 2008 (OPUS)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8937015/ Powell et al. 2022 (GOG-0261)]
-|2005-2006
+|2009-2014
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#FOLFOX4_.26_Cetuximab|FOLFOX4 & Cetuximab]]
+|[[#Ifosfamide_.26_Paclitaxel|Ifosfamide & Paclitaxel]]
-| style="background-color:#d73027" |Inferior OS<sup>1</sup>
+| style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>Median OS: 37 vs 29 mo<br>(HR 0.87, 90% CI 0.70-1.075)
 |-
-|[https://doi.org/10.1200/jco.2009.27.4860 Douillard et al. 2010 (PRIME)]
+|}
-|2006-2008 (C)
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase 3 (C)
+====Chemotherapy====
-|[[#FOLFOX4_.26_Panitumumab|FOLFOX4 & Panitumumab]]
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1, '''given second'''
-| style="background-color:#fc8d59" |Seems to have inferior PFS<sup>2</sup>
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+'''21-day cycle for 6 to 10 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #7, 7/175 {{#subobject:3a58ce|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/JCO.2018.78.3183 Qin et al. 2018 (TAILOR-CRC)]
+|[https://doi.org/10.1200/jco.2001.19.20.4048 Hoskins et al. 2001]
-|2010-NR
+|1995-1998
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#91cf61"|Phase 2
-|[[#FOLFOX4_.26_Cetuximab|FOLFOX4 & Cetuximab]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
-''<sup>1</sup>Reported efficacy for OPUS is based on the 2012 pooled update and is only for KRAS wild-type tumors.''<br>
+''Note: this is the upper limit of carboplatin dosing allowed in Hoskins et al. 2001.''
-''<sup>2</sup>In PRIME, patients with KRAS wild-type tumors receiving this regimen seem to have inferior OS, based on the 2014 update. Conversely, in KRAS mutants, this regimen seems to have superior PFS.''<br>
-''Note: TAILOR required RAS wild-type (not just KRAS). Note that there is another trial named TAILOR in non-small cell lung cancer, so this one has been dubbed TAILOR-CRC.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first, with oxaliplatin on day 1'''
+*[[Carboplatin (Paraplatin)]] AUC 7 IV once on day 1, '''given second'''
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first'''
+'''21-day cycles'''
-'''14-day cycles'''
 </div></div>
 ===References===
-#'''OPUS:''' Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009 Feb 10;27(5):663-71. Epub 2008 Dec 29. [https://doi.org/10.1200/JCO.2008.20.8397 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19114683 PubMed] NCT00125034
+# Hoskins PJ, Swenerton KD, Pike JA, Wong F, Lim P, Acquino-Parsons C, Lee N. Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study. J Clin Oncol. 2001 Oct 15;19(20):4048-53. [https://doi.org/10.1200/jco.2001.19.20.4048 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11600606/ PubMed]
-##'''Update:''' Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011 Jul;22(7):1535-46. Epub 2011 Jan 12. [https://doi.org/10.1093/annonc/mdq632 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21228335 PubMed]
+# Sorbe B, Andersson H, Boman K, Rosenberg P, Kalling M. Treatment of primary advanced and recurrent endometrial carcinoma with a combination of carboplatin and paclitaxel-long-term follow-up. Int J Gynecol Cancer. 2008 Jul-Aug;18(4):803-8. Epub 2007 Oct 18. [https://doi.org/10.1111/j.1525-1438.2007.01094.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17944917/ PubMed]
-##'''Pooled update:''' Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. [https://www.ejcancer.com/article/S0959-8049(12)00209-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22446022 PubMed]
+# Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, Psyrri A, Gaglia A, Kassanos D, Gouveris P, Panayiotidis J, Fountzilas G, Economopoulos T. Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol. 2008 May;109(2):250-4. Epub 2008 Mar 4. [https://doi.org/10.1016/j.ygyno.2008.01.028 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18299146/ PubMed] content property of [https://hemonc.org HemOnc.org]
-#'''PRIME:''' Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. Epub 2010 Oct 4. [https://doi.org/10.1200/jco.2009.27.4860 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20921465 PubMed] NCT00364013
+# '''Retrospective:''' Shechter-Maor G, Bruchim I, Ben-Harim Z, Altaras M, Fishman A. Combined chemotherapy regimen of carboplatin and paclitaxel as adjuvant treatment for papillary serous and clear cell endometrial cancer. Int J Gynecol Cancer. 2009 May;19(4):662-4. [https://doi.org/10.1111/igc.0b013e3181a3d626 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19509567/ PubMed]
-##'''Biomarker analysis:''' Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. [https://doi.org/10.1056/NEJMoa1305275 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24024839 PubMed]
+# '''GOG0209:''' Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, DiSilvestro P, Pearl ML, Argenta PA, Powell MA, Zweizig SL, Warshal DP, Hanjani P, Carney ME, Huang H, Cella D, Zaino R, Fleming GF. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol. 2020 Nov 20;38(33):3841-3850. Epub 2020 Sep 29. [https://doi.org/10.1200/jco.20.01076 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676887/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33078978/ PubMed] [https://clinicaltrials.gov/study/NCT00063999 NCT00063999]
-##'''Update:''' Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jul;25(7):1346-55. Epub 2014 Apr 8. [https://doi.org/10.1093/annonc/mdu141 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24718886 PubMed]
+# '''GOG-0261:''' Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. Epub 2022 Jan 10. [https://doi.org/10.1200/jco.21.02050 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8937015/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35007153/ PubMed] [https://clinicaltrials.gov/study/NCT00954174 NCT00954174]
-#'''TAILOR:''' Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, Li W, Xu N, Lin LZ, Wu Q, Li Y, Yang J, Pan H, Ouyang X, Qiu W, Wu K, Xiong J, Dai G, Liang H, Hu C, Zhang J, Tao M, Yao Q, Wang J, Chen J, Eggleton SP, Liu T. Efficacy and tolerability of first-line cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) versus FOLFOX-4 in patients with RAS wild-type metastatic colorectal cancer: the open-label, randomized, phase III TAILOR trial. J Clin Oncol. 2018 Oct 20;36(30):3031-9. Epub 2018 Sep 10. [https://doi.org/10.1200/JCO.2018.78.3183 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30199311 PubMed] NCT01228734
+# '''RUBY:''' Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. Epub 2023 Mar 27. [https://doi.org/10.1056/nejmoa2216334 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36972026/ PubMed] [https://clinicaltrials.gov/study/NCT03981796 NCT03981796]
-==FOLFOX4 & Cetuximab {{#subobject:5e5bf3|Regimen=1}}==
+#'''NRG GY018:''' Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. Epub 2023 Mar 27. [https://doi.org/10.1056/NEJMoa2302312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10351614/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/36972022/ PubMed] [https://clinicaltrials.gov/study/NCT03914612 NCT03914612]
-FOLFOX4 & Cetuximab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Cetuximab
+#'''DUO-E:''' Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. [https://doi.org/10.1200/jco.23.02132 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37864337/ PubMed] [https://clinicaltrials.gov/study/NCT04269200 NCT04269200]
+==Carboplatin & Paclitaxel (CP) & Dostarlimab {{#subobject:b0e81f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9ec84d|Variant=1}}===
+===Regimen {{#subobject:gic5c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2008.20.8397 Bokemeyer et al. 2008 (OPUS)]
+|[https://doi.org/10.1056/nejmoa2216334 Mirza et al. 2023 (RUBY)]
-|2005-2006
+|2019-2022
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#FOLFOX4|FOLFOX4]]
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 23.5 vs 19.5 mo<br>(HR 0.81, 95% CI 0.69-0.94)
+| style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>OS24: 71.3% vs 56%<br>(HR 0.64, 95% CI 0.46-0.87)
-|-
-|[https://doi.org/10.1200/JCO.2018.78.3183 Qin et al. 2018 (TAILOR-CRC)]
-|2010-NR
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#FOLFOX4|FOLFOX4]]
-| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 20.7 vs 17.8 mo<br>(HR 0.76, 95% CI 0.61-0.96)
 |-
 |}
-''<sup>1</sup>Reported efficacy for OPUS is based on the 2012 pooled update and is only for KRAS wild-type tumors.''<br>
-''TAILOR required RAS wild-type (not just KRAS). Note that there is another trial named TAILOR in non-small cell lung cancer, so this one has been dubbed TAILOR-CRC.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*OPUS: none
-*TAILOR-CRC: Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given second, with oxaliplatin on day 1'''
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given third''' (total dose per cycle: 2000 mg/m<sup>2</sup>)
+**Cycles 1 to 6: AUC 5 IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] as follows:
-====Targeted therapy====
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 1
-*[[Cetuximab (Erbitux)]] '''given first''', as follows:
+====Immunotherapy====
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once on day 8
+*[[Dostarlimab (Jemperli)]] as follows:
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
+**Cycles 1 to 6: 500 mg IV once on day 1
-'''14-day cycles'''
+**Cycles 7 to 32: 1000 mg IV once on day 1
+'''21-day cycle for 6 cycles, then 42-day cycle for up to 26 cycles (3 years)'''
 </div></div>
 ===References===
-#'''OPUS:''' Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009 Feb 10;27(5):663-71. Epub 2008 Dec 29. [https://doi.org/10.1200/JCO.2008.20.8397 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19114683 PubMed] NCT00125034
+# '''RUBY:''' Mirza MR, Chase DM, Slomovitz BM, dePont Christensen R, Novák Z, Black D, Gilbert L, Sharma S, Valabrega G, Landrum LM, Hanker LC, Stuckey A, Boere I, Gold MA, Auranen A, Pothuri B, Cibula D, McCourt C, Raspagliesi F, Shahin MS, Gill SE, Monk BJ, Buscema J, Herzog TJ, Copeland LJ, Tian M, He Z, Stevens S, Zografos E, Coleman RL, Powell MA; RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2145-2158. Epub 2023 Mar 27. [https://doi.org/10.1056/nejmoa2216334 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36972026/ PubMed] [https://clinicaltrials.gov/study/NCT03981796 NCT03981796]
-##'''Update:''' Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, Celik I, Schlichting M, Koralewski P. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011 Jul;22(7):1535-46. Epub 2011 Jan 12. [https://doi.org/10.1093/annonc/mdq632 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21228335 PubMed]
-##'''Pooled update:''' Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. [https://www.ejcancer.com/article/S0959-8049(12)00209-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22446022 PubMed]
+==Carboplatin & Paclitaxel (CP) & Durvalumab {{#subobject:bdta1f|Regimen=1}}==
-#'''TAILOR:''' Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, Li W, Xu N, Lin LZ, Wu Q, Li Y, Yang J, Pan H, Ouyang X, Qiu W, Wu K, Xiong J, Dai G, Liang H, Hu C, Zhang J, Tao M, Yao Q, Wang J, Chen J, Eggleton SP, Liu T. Efficacy and tolerability of first-line cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) versus FOLFOX-4 in patients with RAS wild-type metastatic colorectal cancer: the open-label, randomized, phase III TAILOR trial. J Clin Oncol. 2018 Oct 20;36(30):3031-9. Epub 2018 Sep 10. [https://doi.org/10.1200/JCO.2018.78.3183 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30199311 PubMed] NCT01228734
-==FOLFOX4 & Panitumumab {{#subobject:486271|Regimen=1}}==
-FOLFOX4 & Panitumumab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Panitumumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d862a3|Variant=1}}===
+===Regimen {{#subobject:duc5c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2009.27.4860 Douillard et al. 2010 (PRIME)]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ Westin et al. 2023 (DUO-E)]
-|2006-2008 (C)
+|rowspan=2|2020-06-02 to 2022-04-20
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
-|[[#FOLFOX4|FOLFOX4]]
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 23.8 vs 19.4 mo<br>(HR 0.83, 95% CI 0.70-0.98)
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 10.2 vs 9.6 mo<br>(HR 0.71, 95% CI 0.57-0.89)<br><br>Superior dMMR subgroup PFS<sup>1</sup> (secondary endpoint)<br>Median PFS: NYR vs 7 mo<br>(HR 0.42, 95% CI 0.22-0.80)
+|-
+|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Olaparib.2C_Durvalumab|CP, Olaparib, Durvalumab]]
+| style="background-color:#d3d3d3" |Not formally compared
 |-
 |}
-''<sup>1</sup>In KRAS wild-type patients, this regimen seems to have superior OS, based on the exploratory analysis in the 2014 update.''
+''<sup>1</sup>PFS analysis of the dMMR subgroup was prespecified; FDA approval is for this subgroup.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m<sup>2</sup>)
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2
+**Cycles 1 to 6: AUC 5 to 6 IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
-====Targeted therapy====
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 1
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV once on day 1, '''given first'''
+====Immunotherapy====
-**Infusion times are 1 hour for cycle 1, then if tolerated, 30 minutes for cycle 2 and later
+*[[Durvalumab (Imfinzi)]] as follows:
-'''14-day cycles'''
+**Cycles 1 to 6: 1120 mg IV once on day 1
+**Cycle 7 onwards: 1500 mg IV once on day 1
+'''21-day cycle for 6 cycles, then 28-day cycles'''
 </div></div>
 ===References===
-<!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; the 2008 Gastrointestinal Cancers Symposium, January 25-27, 2008, Orlando, FL; the joint 15th Congress of the European Cancer Organisation and 34th Congress of the European Society for Medical Oncology, September 20-24, 2009, Berlin, Germany; the 6th Annual Meeting of the International Society of Gastrointestinal Oncology, October 1-3, 2009, Philadelphia, PA; the 2009 National Cancer Research Institute Cancer Conference, October 4-7, 2009, Birmingham, United Kingdom; and the 2010 Gastrointestinal Cancers Symposium, January 22-24, 2010, Orlando, FL. -->
+#'''DUO-E:''' Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. [https://doi.org/10.1200/jco.23.02132 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37864337/ PubMed] [https://clinicaltrials.gov/study/NCT04269200 NCT04269200]
-#'''PRIME:''' Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. Epub 2010 Oct 4. [https://doi.org/10.1200/jco.2009.27.4860 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20921465 PubMed] NCT00364013
-##'''Biomarker analysis:''' Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. [https://doi.org/10.1056/NEJMoa1305275 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24024839 PubMed]
+==Carboplatin & Paclitaxel (CP), Olaparib, Durvalumab {{#subobject:bdokdf|Regimen=1}}==
-##'''Update:''' Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jul;25(7):1346-55. Epub 2014 Apr 8. [https://doi.org/10.1093/annonc/mdu141 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24718886 PubMed]
-==mFOLFOX6-B {{#subobject:8ugz86|Regimen=1}}==
-mFOLFOX6-B: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>B</u>'''evacizumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8baf2c|Variant=1}}===
+===Regimen {{#subobject:lod5c0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545896/ Venook et al. 2017 (CALGB 80405)]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ Westin et al. 2023 (DUO-E)]
-|rowspan=2|2005-2012
+|rowspan=2|2020-06-02 to 2022-04-20
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
-|1. [[#mFOLFOX6_.26_Panitumumab|mFOLFOX6 & Panitumumab]]<br>2. [[#FOLFIRI_.26_Panitumumab_88|FOLFIRI & Panitumumab]]
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 15.1 vs 9.6 mo<br>(HR 0.55, 95% CI 0.43-0.69)
 |-
-|3. [[#mFOLFOX6.2C_Bevacizumab.2C_Cetuximab_99|mFOLFOX6, Bevacizumab, Cetuximab]]<br>4. [[#FOLFIRI.2C_Bevacizumab.2C_Cetuximab_99|FOLFIRI, Bevacizumab, Cetuximab]]
+|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Durvalumab|CP & Durvalumab|CP & Durvalumab]]
-| style="background-color:#d3d3d3" |Not reported
+| style="background-color:#d3d3d3" |Not formally compared
-|-
-|Awaiting publication (PARADIGM<sub>CRC</sub>)
-|2015-2022
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#mFOLFOX6_.26_Panitumumab|mFOLFOX6 & Panitumumab]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
+**Cycles 1 to 6: AUC 5 to 6 IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 1
+====Immunotherapy====
+*[[Durvalumab (Imfinzi)]] as follows:
+**Cycles 1 to 6: 1120 mg IV once on day 1
+**Cycle 7 onwards: 1500 mg IV once on day 1
 ====Targeted therapy====
-*[[Bevacizumab (Avastin)]] 5 mg/kg IV once on day 1
+*[[Olaparib (Lynparza)]] as follows:
-'''14-day cycles'''
+**Cycle 7 onwards: 300 mg PO twice per day on days 1 to 28
+'''21-day cycle for 6 cycles, then 28-day cycles'''
 </div></div>
 ===References===
-#'''CALGB 80405:''' Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. [https://jamanetwork.com/journals/jama/fullarticle/2632502 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545896/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632865 PubMed] NCT00265850
+#'''DUO-E:''' Westin SN, Moore K, Chon HS, Lee JY, Thomes Pepin J, Sundborg M, Shai A, de la Garza J, Nishio S, Gold MA, Wang K, McIntyre K, Tillmanns TD, Blank SV, Liu JH, McCollum M, Contreras Mejia F, Nishikawa T, Pennington K, Novak Z, De Melo AC, Sehouli J, Klasa-Mazurkiewicz D, Papadimitriou C, Gil-Martin M, Brasiuniene B, Donnelly C, Del Rosario PM, Liu X, Van Nieuwenhuysen E; DUO-E Investigators. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J Clin Oncol. 2024 Jan 20;42(3):283-299. Epub 2023 Oct 21. [https://doi.org/10.1200/jco.23.02132 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37864337/ PubMed] [https://clinicaltrials.gov/study/NCT04269200 NCT04269200]
-#'''PARADIGM<sub>CRC</sub>:''' NCT02394795
-==mFOLFOX6 & Cetuximab {{#subobject:12d786|Regimen=1}}==
+==Carboplatin & Paclitaxel (CP) & Pembrolizumab {{#subobject:b0bjc2|Regimen=1}}==
-mFOLFOX6 & Cetuximab: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Cetuximab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8baf2c|Variant=1}}===
+===Regimen {{#subobject:ug1cx0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545896/ Venook et al. 2017 (CALGB 80405)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10351614/ Eskander et al. 2023 (NRG GY018)]
-|rowspan=2|2005-2012
+|2019-07 to 2022-12
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|1. [[#mFOLFOX6_.26_Panitumumab|mFOLFOX6 & Panitumumab]]<br>2. [[#FOLFIRI_.26_Panitumumab_88|FOLFIRI & Panitumumab]]
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior PFS<sup>1</sup> (co-primary endpoint)<br>PFS12: 74% vs 38%<br>(HR 0.30, 95% CI 0.19-0.48)<br><br>Superior PFS<sup>2</sup> (co-primary endpoint)<br>Median PFS: 13.1 vs 8.7 mo<br>(HR 0.54, 95% CI 0.41-0.71)
-|-
-|3. [[#mFOLFOX6.2C_Bevacizumab.2C_Cetuximab_99|mFOLFOX6, Bevacizumab, Cetuximab]]<br>4. [[#FOLFIRI.2C_Bevacizumab.2C_Cetuximab_99|FOLFIRI, Bevacizumab, Cetuximab]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://www.ejcancer.com/article/S0959-8049(18)30938-9 Aranda et al. 2018 (MACRO-2)]
-|2010-NR
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
 |}
-''Note: In CALGB 80405, the arm receiving bevacizumab and cetuximab was terminated early.''
+''<sup>1</sup>Reported efficacy is for the dMMR cohort.''<br>
-<div class="toccolours" style="background-color:#fdcdac">
+''<sup>2</sup>Reported efficacy is for the pMMR cohort.''
-====Biomarker eligibility criteria====
-*CALGB 80405: Wild-type KRAS (codons 12 & 13)
-*MACRO-2: Wild-type KRAS (exons 3 & 4), Wild-type NRAS (exons 2 to 4)
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+**Cycles 1 to 6: AUC 5 IV over 30 to 60 minutes once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] as follows:
-====Targeted therapy====
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
-*[[Cetuximab (Erbitux)]] as follows, '''given first''':
+====Immunotherapy====
-**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once on day 8
+*[[Pembrolizumab (Keytruda)]] as follows:
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
+**Cycles 1 to 6: 200 mg IV over 30 minutes once on day 1
-'''14-day cycles (see below)'''
+**Cycles 7 to 20: 400 mg IV over 30 minutes once on day 1
-</div>
+'''21-day cycle for 6 cycles, then 42-day cycle for 14 cycles'''
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*MACRO-2, after 8 cycles: continued [[#mFOLFOX6_.26_Cetuximab_2|mFOLFOX6 & Cetuximab]] until progression versus [[#Cetuximab_monotherapy|cetuximab]] maintenance
 </div></div>
 ===References===
-#'''CALGB 80405:''' Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, Berry S, Polite BN, O'Reilly EM, Goldberg RM, Hochster HS, Schilsky RL, Bertagnolli MM, El-Khoueiry AB, Watson P, Benson AB 3rd, Mulkerin DL, Mayer RJ, Blanke C. Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial. JAMA. 2017 Jun 20;317(23):2392-2401. [https://jamanetwork.com/journals/jama/fullarticle/2632502 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545896/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28632865 PubMed] NCT00265850
+#'''NRG GY018:''' Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel R, Shahin MS, Cantuaria GH, Girda E, Mathews C, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Al Baghdadi T, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med. 2023 Jun 8;388(23):2159-2170. Epub 2023 Mar 27. [https://doi.org/10.1056/NEJMoa2302312 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10351614/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/36972022/ PubMed] [https://clinicaltrials.gov/study/NCT03914612 NCT03914612]
-#'''MACRO-2:''' Aranda E, García-Alfonso P, Benavides M, Sánchez Ruiz A, Guillén-Ponce C, Safont MJ, Alcaide J, Gómez A, López R, Manzano JL, Méndez Ureña M, Sastre J, Rivera F, Grávalos C, García T, Martín-Valadés JI, Falcó E, Navalón M, González Flores E, Ma García Tapiador A, Ma López Muñoz A, Barrajón E, Reboredo M, García Teijido P, Viudez A, Cárdenas N, Díaz-Rubio E; Spanish Cooperative Group for the Treatment of Digestive Tumours. First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: phase II randomised MACRO2 TTD study. Eur J Cancer. 2018 Sep;101:263-272. Epub 2018 Jul 24. [https://www.ejcancer.com/article/S0959-8049(18)30938-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30054049 PubMed] NCT01161316
-==mFOLFOX6 & Panitumumab {{#subobject:avn786|Regimen=1}}==
+==Carboplatin & Paclitaxel (CP) & Trastuzumab {{#subobject:b0ejgf|Regimen=1}}==
-mFOLFOX6 & Panitumumab: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Panitumumab
+CP+T: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, '''<u>T</u>'''rastuzumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8bukqc|Variant=1}}===
+===Regimen {{#subobject:7ab110|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9426812/ Rossini et al. 2022 (TRIPLETE)]
+|[https://doi.org/10.1200/jco.2017.76.5966 Fader et al. 2018]
-|2017-2021
+|2011-2017
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|[[#mFOLFOXIRI_.26_Panitumumab_99|mFOLFOXIRI & Panitumumab]]
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+| style="background-color:#1a9850" |Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 12.9 vs 8 mo<br>(HR 0.46, 90% CI 0.28-0.76)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2020 update.''
 <div class="toccolours" style="background-color:#fdcdac">
 ====Biomarker eligibility criteria====
-*Wild-type KRAS (exons 2 to 4), wild-type NRAS (exons 2 to 4), wild-type BRAF codon 600
+*HER2 overexpression
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, '''given third''', then 2400 mg/m<sup>2</sup> IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1, '''given second'''
+**Cycles 1 to 6: AUC 5 IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] as follows:
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 ====Targeted therapy====
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 30 to 60 minutes once on day 1, '''given first'''
+*[[Trastuzumab (Herceptin)]] as follows:
-'''14-day cycles'''
+**Cycle 1: 8 mg/kg IV once on day 1
+**Cycle 2 onwards: 6 mg/kg IV once on day 1
+'''21-day cycles'''
 </div></div>
 ===References===
-#'''TRIPLETE:''' Rossini D, Antoniotti C, Lonardi S, Pietrantonio F, Moretto R, Antonuzzo L, Boccaccino A, Morano F, Brugia M, Pozzo C, Marmorino F, Bergamo F, Tamburini E, Passardi A, Randon G, Murgioni S, Borelli B, Buonadonna A, Giordano M, Fontanini G, Conca V, Formica V, Aglietta M, Bordonaro R, Aprile G, Masi G, Boni L, Cremolini C. Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO. J Clin Oncol. 2022 Sep 1;40(25):2878-2888. Epub 2022 Jun 6. [https://doi.org/10.1200/jco.22.00839 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc9426812/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35666229/ PubMed] NCT03231722
+#Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers SK, Secord AA, Havrilesky L, O'Malley DM, Backes F, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi KS, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Versus Carboplatin-Paclitaxel-Trastuzumab in Uterine Serous Carcinomas That Overexpress Human Epidermal Growth Factor Receptor 2/neu. J Clin Oncol. 2018 Jul 10;36(20):2044-2051. Epub 2018 Mar 27. [https://doi.org/10.1200/jco.2017.76.5966 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29584549/ PubMed] [https://clinicaltrials.gov/study/NCT01367002 NCT01367002]
-==mFOLFOXIRI & Cetuximab (L-Leucovorin){{#subobject:9bf7|Regimen=1}}==
+##'''Update:''' Fader AN, Roque DM, Siegel E, Buza N, Hui P, Abdelghany O, Chambers S, Secord AA, Havrilesky L, O'Malley DM, Backes FJ, Nevadunsky N, Edraki B, Pikaart D, Lowery W, ElSahwi K, Celano P, Bellone S, Azodi M, Litkouhi B, Ratner E, Silasi DA, Schwartz PE, Santin AD. Randomized Phase II Trial of Carboplatin-Paclitaxel Compared with Carboplatin-Paclitaxel-Trastuzumab in Advanced (Stage III-IV) or Recurrent Uterine Serous Carcinomas that Overexpress Her2/Neu (NCT01367002): Updated Overall Survival Analysis. Clin Cancer Res. 2020 Aug 1;26(15):3928-3935. Epub 2020 Jun 29. [https://doi.org/10.1158/1078-0432.ccr-20-0953 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8792803/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32601075/ PubMed]
-mFOLFOXIRI & Cetuximab: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>IRI</u>'''notecan, Cetuximab
+==Carboplatin & Pegylated liposomal doxorubicin {{#subobject:c8ff00|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:19365|Variant=1}}===
+===Regimen {{#subobject:d48f39|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 33%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885260/ Cremolini et al. 2018 (MACBETH)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359926/ Pignata et al. 2007 (END-1)]
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
+|2002-2005
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
-''Note: 5-FU instructions are unusual in that no bolus is given.''
+''Note: All patients received 3 cycles of therapy. If there was no unacceptable toxicity, patients with stable or responsive disease received an additional 3 cycles.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 1, '''given fourth''' (total dose per cycle: 2400 mg/m<sup>2</sup>)
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given first'''
-*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given third, with oxaliplatin'''
+*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given third, with L-leucovorin'''
+'''28-day cycle for 3 to 6 cycles'''
-*[[Irinotecan (Camptosar)]] 130 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
-====Targeted therapy====
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
-'''14-day cycle for 8 cycles'''
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
+<div class="toccolours" style="background-color:#fff2ae">
-====Subsequent treatment====
+====Dose and schedule modifications====
-*MACBETH, if deemed resectable: [[Surgery#Colorectal_cancer_surgery|Surgery]]
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] were not recommended for prophylaxis, but were allowed for grade 4 neutropenia
-*MACBETH, if deemed unresectable: [[#Cetuximab_monotherapy|Cetuximab]] versus [[#Bevacizumab_monotherapy_99|bevacizumab]] maintenance
 </div></div>
 ===References===
-#'''MACBETH:''' Cremolini C, Antoniotti C, Lonardi S, Aprile G, Bergamo F, Masi G, Grande R, Tonini G, Mescoli C, Cardellino GG, Coltelli L, Salvatore L, Corsi DC, Lupi C, Gemma D, Ronzoni M, Dell'Aquila E, Marmorino F, Di Fabio F, Mancini ML, Marcucci L, Fontanini G, Zagonel V, Boni L, Falcone A. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a randomized phase 2 clinical trial. JAMA Oncol. 2018 Apr 1;4(4):529-536. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2672387 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885260/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29450468 PubMed] NCT02295930
+# '''END-1:''' Pignata S, Scambia G, Pisano C, Breda E, Di Maio M, Greggi S, Ferrandina G, Lorusso D, Zagonel V, Febbraro A, Riva N, De Rosa V, Gallo C, Perrone F; Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies Group. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer. 2007 Jun 4;96(11):1639-43. Epub 2007 May 8. [https://doi.org/10.1038/sj.bjc.6603787 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359926/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17486128/ PubMed]
-==FOLFOXIRI & Panitumumab {{#subobject:9bf7|Regimen=1}}==
-FOLFOXIRI & Panitumumab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>IRI</u>'''notecan, Panitumumab
+==Cisplatin & Doxorubicin {{#subobject:7f9e48|Regimen=1}}==
+AP: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>P</u>'''latinol (Cisplatin)
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 50/45 {{#subobject:1748e2|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2004.07.184 Fleming et al. 2004a (GOG 177)]
+|1998-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel|Cisplatin, Doxorubicin, Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|}
+''Note: body surface area was capped at 2 m<sup>2</sup>. This dosage was for patients with previous pelvic radiation or who were greater than 65 years old.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 60 minutes once on day 1, '''given second'''
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 90 mg) IV once on day 1, '''given first'''
+'''21-day cycle for 7 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 50/60, capped BSA {{#subobject:3b1876|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2004.07.184 Fleming et al. 2004a (GOG 177)]
+|1998-2000
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel|Cisplatin, Doxorubicin, Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|}
+''Note: body surface area was capped at 2 m<sup>2</sup>.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 60 minutes once on day 1, '''given second'''
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> (maximum dose of 120 mg) IV once on day 1, '''given first'''
+'''21-day cycle for 7 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 50/60, no cap on BSA {{#subobject:5baa3b|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1093/annonc/mdh316 Fleming et al. 2004 (GOG 163)]
+|1996-1998
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Doxorubicin_.26_Paclitaxel_.28AT.29_999|Doxorubicin & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|[https://doi.org/10.1200/JCO.2004.02.088 Thigpen et al. 2004 (GOG 107)]
+|NR
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Doxorubicin_monotherapy|Doxorubicin]]
+| style="background-color:#91cf60" |Seems to have superior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
+====Supportive therapy====
+*Normal saline at 500 mL/H for 2 hours prior to and after cisplatin
+'''21-day cycle for up to 8 cycles'''
+</div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:19365|Variant=1}}===
+===Regimen variant #4, 60/60 {{#subobject:828296|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.19.01340 Modest et al. 2019 (VOLFI)]
+|[https://doi.org/10.1200/JCO.2003.10.083 Gallion et al. 2003 (GOG 139)]
-|2011-2016
+|1993-1996
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#FOLFIRINOX|FOLFOXIRI]]
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]; chronomodulated
-| style="background-color:#1a9850" |Superior ORR
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Wild-type KRAS, Wild-type NRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours, started on day 1 (total dose per cycle: 3000 mg/m<sup>2</sup>)
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for up to 8 cycles'''
-*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
-====Targeted therapy====
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV once on day 1
-'''14-day cycle until POD or resectability or to max 12 cycles'''
 </div></div>
 ===References===
-#'''VOLFI:''' Modest DP, Martens UM, Riera-Knorrenschild J, Greeve J, Florschütz A, Wessendorf S, Ettrich T, Kanzler S, Nörenberg D, Ricke J, Seidensticker M, Held S, Buechner-Steudel P, Atzpodien J, Heinemann V, Seufferlein T, Tannapfel A, Reinacher-Schick AC, Geissler M. FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). J Clin Oncol. 2019 Dec 10;37(35):3401-3411. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01340 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31609637 PubMed] NCT01328171
+# '''GOG 139:''' Gallion HH, Brunetto VL, Cibull M, Lentz SS, Reid G, Soper JT, Burger RA, Andersen W; Gynecologic Oncology Group. Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2003 Oct 15;21(20):3808-13. [https://doi.org/10.1200/JCO.2003.10.083 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14551299/ PubMed]
-=Maintenance after first-line therapy=
+# '''GOG 177:''' Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. [https://doi.org/10.1200/jco.2004.07.184 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15169803/ PubMed] [https://clinicaltrials.gov/study/NCT00003691 NCT00003691]
-==Bevacizumab monotherapy {{#subobject:ahag4f|Regimen=1}}==
+# '''GOG 163:''' Fleming GF, Filiaci VL, Bentley RC, Herzog T, Sorosky J, Vaccarello L, Gallion H. Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol. 2004 Aug;15(8):1173-8. [https://doi.org/10.1093/annonc/mdh316 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15277255/ PubMed]
+# '''GOG 107:''' Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Oct 1;22(19):3902-8. [https://doi.org/10.1200/JCO.2004.02.088 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15459211/ PubMed]
+==Cisplatin, Doxorubicin, Paclitaxel {{#subobject:b61c1e|Regimen=1}}==
+TAP: '''<u>T</u>'''axol (Paclitaxel), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin)
+<br>CDP: '''<u>C</u>'''isplatin, '''<u>D</u>'''oxorubicin, '''<u>P</u>'''aclitaxel
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:a72hg6|Variant=1}}===
+===Regimen {{#subobject:68777b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1093/annonc/mdv490 Hagman et al. 2015 (Nordic ACT2)]
+|[https://doi.org/10.1200/jco.2004.07.184 Fleming et al. 2004 (GOG 177)]
-|2010-2012
+|1998-2000
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]
+|style="background-color:#91cf60"|Seems to have superior OS (primary endpoint)<br>Median OS: 15.3 vs 12.3 mo<br>(HR 0.75, 95% CI 0.57-0.99)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676887/ Miller et al. 2020 (GOG0209)]
+|2003-2009
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Erlotinib_.26_Bevacizumab_99|Erlotinib & Bevacizumab]]
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|TC]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+| style="background-color:#eeee01" |Non-inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
+''Note: in GOG 177, body surface area was capped at 2 m<sup>2</sup>.''
-====Biomarker eligibility criteria====
-*Wild-type KRAS
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Chemotherapy====
-*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
-'''21-day cycles'''
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> IV once on day 1, '''given first'''
+*[[Paclitaxel (Taxol)]] 160 mg/m<sup>2</sup> IV over 3 hours once on day 2
+====Supportive therapy====
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 12
+'''21-day cycle for 7 cycles'''
 </div></div>
 ===References===
-#'''Nordic ACT2:''' Hagman H, Frödin JE, Berglund Å, Sundberg J, Vestermark LW, Albertsson M, Fernebro E, Johnsson A. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial. Ann Oncol. 2016 Jan;27(1):140-7. Epub 2015 Oct 19. [https://doi.org/10.1093/annonc/mdv490 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26483047/ PubMed] NCT01229813
+# '''GOG 177:''' Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Jun 1;22(11):2159-66. [https://doi.org/10.1200/jco.2004.07.184 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15169803/ PubMed] [https://clinicaltrials.gov/study/NCT00003691 NCT00003691]
-==Cetuximab monotherapy {{#subobject:afad4f|Regimen=1}}==
+# '''GOG0209:''' Miller DS, Filiaci VL, Mannel RS, Cohn DE, Matsumoto T, Tewari KS, DiSilvestro P, Pearl ML, Argenta PA, Powell MA, Zweizig SL, Warshal DP, Hanjani P, Carney ME, Huang H, Cella D, Zaino R, Fleming GF. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol. 2020 Nov 20;38(33):3841-3850. Epub 2020 Sep 29. [https://doi.org/10.1200/jco.20.01076 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676887/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33078978/ PubMed] [https://clinicaltrials.gov/study/NCT00063999 NCT00063999]
+==Cisplatin & Ifosfamide {{#subobject:ac4ecc|Regimen=1}}==
+CIM: '''<u>C</u>'''isplatin, '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 250 mg/m<sup>2</sup> weekly {{#subobject:a72650|Variant=1}}===
+===Regimen {{#subobject:a26ea4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ejcancer.com/article/S0959-8049(18)30938-9 Aranda et al. 2018 (MACRO-2)]
+|[https://doi.org/10.1006/gyno.2000.6001 Sutton et al. 2000 (GOG 108)]
-|2010-NR
+|1989-1996
-| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|[[#mFOLFOX6_.26_Cetuximab_2|mFOLFOX6 & Cetuximab]]
+|[[#Ifosfamide_monotherapy|Ifosfamide]]
-| style="background-color:#eeee01" |Non-inferior PFS
+| style="background-color:#91cf60" |Seems to have superior PFS (co-primary endpoint)
 |-
 |}
-''Note: regimen details are from ClinicalTrials.gov; they were not present in the abstract or the manuscript.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Wild-type KRAS, Wild-type NRAS
-<div class="toccolours" style="background-color:#cbd5e8">
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Preceding treatment====
+====Chemotherapy====
-*[[#mFOLFOX6_.26_Cetuximab_2|mFOLFOX6 & Cetuximab]] x 8
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
-</div>
+*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
+====Supportive therapy====
+*[[Mesna (Mesnex)]]
+'''21-day cycle for 8 cycles'''
+</div></div>
+===References===
+# '''GOG 108:''' Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol. 2000 Nov;79(2):147-53. [https://doi.org/10.1006/gyno.2000.6001 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11063636/ PubMed]
+==Cisplatin & Paclitaxel {{#subobject:89fd88|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:b3c8fd|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1006/gyno.2000.5827 Dimopoulos et al. 2000]
+|1995-06 to 1997-05
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Chemotherapy====
-*[[Cetuximab (Erbitux)]] 250 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
-'''7-day cycles'''
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-</div></div><br>
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 25 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*900 mL normal saline mixed with 100 mL mannitol given over 1 hour prior to cisplatin
+*2 liters NS with potassium & magnesium after cisplatin
+*"Appropriate antiemetics"
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 5 and continuing until WBC greater than 10,000 x 10<sup>9</sup>/L
+'''21-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+# Dimopoulos MA, Papadimitriou CA, Georgoulias V, Moulopoulos LA, Aravantinos G, Gika D, Karpathios S, Stamatelopoulos S. Paclitaxel and cisplatin in advanced or recurrent carcinoma of the endometrium: long-term results of a phase II multicenter study. Gynecol Oncol. 2000 Jul;78(1):52-7. [https://doi.org/10.1006/gyno.2000.5827 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10873410/ PubMed]
+==Dactinomycin monotherapy {{#subobject:97a01a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 500 mg/m<sup>2</sup> q2wk {{#subobject:3d7e64|Variant=1}}===
+===Regimen {{#subobject:2019ab|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 33%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885260/ Cremolini et al. 2018 (MACBETH)]
+|[https://doi.org/10.1006/gyno.1999.5652 Moore et al. 1999]
-| style="background-color:#91cf61" |Randomized Phase 2
+|1996
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
-''Note: this was a non-comparative study.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Wild-type KRAS, Wild-type NRAS
-<div class="toccolours" style="background-color:#cbd5e8">
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Preceding treatment====
+====Chemotherapy====
-*[[#mFOLFOXIRI_.26_Cetuximab_.28L-Leucovorin.29|mFOLFOXIRI & Cetuximab]] x 8
+*[[Dactinomycin (Cosmegen)]] 2 mg/m<sup>2</sup> IV over 15 minutes once on day 1
-</div>
+'''28-day cycles'''
+</div></div>
+===References===
+# Moore DH, Blessing JA, Dunton C, Buller RE, Reid GC; Gynecologic Oncology Group. Dactinomycin in the treatment of recurrent or persistent endometrial carcinoma: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol. 1999 Dec;75(3):473-5. [https://doi.org/10.1006/gyno.1999.5652 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10600310/ PubMed]
+==Dostarlimab monotherapy {{#subobject:ejg8a3|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:5dnfj9|Variant=1}}===
+{| class="wikitable sortable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7530821/ Oaknin et al. 2020 (GARNET<sub>endometrial</sub>)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-256-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|2017-2019
+| style="background-color:#91cf61" |Phase 1, >20 pts in this cohort (RT)
+|-
+|}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Immunotherapy====
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV once on day 1
+*[[Dostarlimab (Jemperli)]] as follows:
-'''14-day cycles'''
+**Cycles 1 to 4: 500 mg IV over 30 minutes once on day 1
+**Cycle 5 onwards: 1000 mg IV over 30 minutes once on day 1
+'''21-day cycle for 4 cycles, then 42-day cycles'''
 </div></div>
 ===References===
-#'''MACBETH:''' Cremolini C, Antoniotti C, Lonardi S, Aprile G, Bergamo F, Masi G, Grande R, Tonini G, Mescoli C, Cardellino GG, Coltelli L, Salvatore L, Corsi DC, Lupi C, Gemma D, Ronzoni M, Dell'Aquila E, Marmorino F, Di Fabio F, Mancini ML, Marcucci L, Fontanini G, Zagonel V, Boni L, Falcone A. Activity and safety of cetuximab plus modified FOLFOXIRI followed by maintenance with cetuximab or bevacizumab for RAS and BRAF wild-type metastatic colorectal cancer: a randomized phase 2 clinical trial. JAMA Oncol. 2018 Apr 1;4(4):529-536. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2672387 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885260/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29450468 PubMed] NCT02295930
+#'''GARNET<sub>endometrial</sub>:''' Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R. Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):1766-1772. Epub 2020 Oct 1. [https://doi.org/10.1001/jamaoncol.2020.4515 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7530821/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33001143/ PubMed] [https://clinicaltrials.gov/study/NCT02715284 NCT02715284]
-#'''MACRO-2:''' Aranda E, García-Alfonso P, Benavides M, Sánchez Ruiz A, Guillén-Ponce C, Safont MJ, Alcaide J, Gómez A, López R, Manzano JL, Méndez Ureña M, Sastre J, Rivera F, Grávalos C, García T, Martín-Valadés JI, Falcó E, Navalón M, González Flores E, Ma García Tapiador A, Ma López Muñoz A, Barrajón E, Reboredo M, García Teijido P, Viudez A, Cárdenas N, Díaz-Rubio E; Spanish Cooperative Group for the Treatment of Digestive Tumours. First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: phase II randomised MACRO2 TTD study. Eur J Cancer. 2018 Sep;101:263-272. Epub 2018 Jul 24. [https://www.ejcancer.com/article/S0959-8049(18)30938-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30054049 PubMed] NCT01161316
+##'''Update:''' Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, Sabatier R, O'Malley DM, Samouelian V, Boni V, Duska L, Ghamande S, Ghatage P, Kristeleit R, Leath C III, Guo W, Im E, Zildjian S, Han X, Duan T, Veneris J, Pothuri B. Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. J Immunother Cancer. 2022 Jan;10(1):e003777. [https://doi.org/10.1136/jitc-2021-003777 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8785197/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35064011/ PubMed]
-=Advanced or metastatic disease, second-line=
+##'''PRO analysis:''' Kristeleit R, Mathews C, Redondo A, Boklage S, Hanlon J, Im E, Brown J. Patient-reported outcomes in the GARNET trial in patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer treated with dostarlimab. Int J Gynecol Cancer. 2022 Aug 16;32(10):1250–7. [https://doi.org/10.1136/ijgc-2022-003492 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9554028/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35973737/ PubMed]
-==FOLFIRI & Panitumumab {{#subobject:8c0093|Regimen=1}}==
-FOLFIRI & Panitumumab: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan, Panitumumab
+==Doxorubicin monotherapy {{#subobject:e5b103|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:ebf6e5|Variant=1}}===
+===Regimen variant #1, 7 cycles {{#subobject:5dn1e9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2009.27.6055 Peeters et al. 2010 (20050181)]
+|[https://doi.org/10.1093/annonc/mdg112 Aapro et al. 2003 (EORTC 55872)]
-|2006-2008
+|1988-1994
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#FOLFIRI|FOLFIRI]]
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]
-| style="background-color:#91cf60" |Seems to have superior PFS<sup>1</sup><br>Median PFS: 6.7 vs 4.9 mo<br>(HR 0.82, 95% CI 0.69-0.97)
+| style="background-color:#fee08b" |Might have inferior OS
 |-
 |}
-''<sup>1</sup>Reported efficacy is for wild-type KRAS, only, and is based on the 2014 update.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*None
-<div class="toccolours" style="background-color:#fdcdac">
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Prior treatment criteria====
+====Chemotherapy====
-*First-line fluoropyrimidine-based chemotherapy, with progression
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
-</div>
+'''28-day cycle for up to 7 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 8 cycles {{#subobject:5d91e9|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://pubmed.ncbi.nlm.nih.gov/369691 Thigpen et al. 1979]
+|NR
+| style="background-color:#91cf61" |Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1002/1097-0142(19830815)52:4%3C626::AID-CNCR2820520409%3E3.0.CO;2-E Omura et al. 1983 (GOG 21)]
+|1973-1979
+|style="background-color:#1a9851"|Randomized (C)
+|[[#Dacarbazine_.26_Doxorubicin_999|Dacarbazine & Doxorubicin]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|[https://doi.org/10.1002/1097-0142(19850415)55:8%3C1648::AID-CNCR2820550806%3E3.0.CO;2-7 Muss et al. 1985 (GOG 42)]
+|1979-1982
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_999|Cyclophosphamide & Doxorubicin (AC)]]
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+|-
+|[https://doi.org/10.1200/JCO.1994.12.7.1408 Thigpen et al. 1994 (GOG 48)]
+|1979-1985
+|style="background-color:#1a9851"|Randomized (C)
+|[[#Cyclophosphamide_.26_Doxorubicin_.28AC.29_999|Cyclophosphamide & Doxorubicin (AC)]]
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+|-
+|[https://doi.org/10.1200/JCO.2004.02.088 Thigpen et al. 2004 (GOG 107)]
+|NR
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]
+|style="background-color:#fc8d59"|Seems to have inferior PFS
+|-
+|[https://doi.org/10.1056/nejmoa2108330 Makker et al. 2022 (KEYNOTE-775)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Lenvatinib_.26_Pembrolizumab|Lenvatinib & Pembrolizumab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second, with irinotecan'''
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+'''21-day cycle for up to 8 cycles'''
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1, '''given second, with leucovorin'''
-====Targeted therapy====
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes once on day 1, '''given first'''
-'''14-day cycles'''
 </div></div>
 ===References===
-#'''20050181:''' Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. [https://doi.org/10.1200/jco.2009.27.6055 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20921462 PubMed] NCT00339183
+# Thigpen JT, Buchsbaum HJ, Mangan C, Blessing JA; Gynecologic Oncology Group. Phase II trial of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Cancer Treat Rep. 1979 Jan;63(1):21-7. [https://pubmed.ncbi.nlm.nih.gov/369691/ PubMed]
-##'''Update:''' Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tian Y, Sidhu R. Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer. Ann Oncol. 2014 Jan;25(1):107-16. Erratum in: Ann Oncol. 2014 Mar;25(3):757. [https://doi.org/10.1093/annonc/mdt523 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24356622 PubMed]
+# '''GOG 21:''' Omura GA, Major FJ, Blessing JA, Sedlacek TV, Thigpen JT, Creasman WT, Zaino RJ. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer. 1983 Aug 15;52(4):626-32. [https://doi.org/10.1002/1097-0142(19830815)52:4%3C626::AID-CNCR2820520409%3E3.0.CO;2-E link to original article] [https://pubmed.ncbi.nlm.nih.gov/6344983/ PubMed]
-==Irinotecan monotherapy {{#subobject:d4d4f9|Regimen=1}}==
+# '''GOG 42:''' Muss HB, Bundy B, DiSaia PJ, Homesley HD, Fowler WC Jr, Creasman W, Yordan E. Treatment of recurrent or advanced uterine sarcoma: a randomized trial of doxorubicin versus doxorubicin and cyclophosphamide (a phase III trial of the Gynecologic Oncology Group). Cancer. 1985 Apr 15;55(8):1648-53. [https://doi.org/10.1002/1097-0142(19850415)55:8%3C1648::AID-CNCR2820550806%3E3.0.CO;2-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3884128/ PubMed]
-===Example orders===
+# '''GOG 48:''' Thigpen JT, Blessing JA, DiSaia PJ, Yordan E, Carson LF, Evers C. A randomized comparison of doxorubicin alone versus doxorubicin plus cyclophosphamide in the management of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1994 Jul;12(7):1408-14. [https://doi.org/10.1200/JCO.1994.12.7.1408 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8021731/ PubMed]
-*[[Example orders for Irinotecan (Camptosar) in colon cancer]]
+# '''EORTC 55872:''' Aapro MS, van Wijk FH, Bolis G, Chevallier B, van der Burg ME, Poveda A, Freire de Oliveira C, Tumolo S, Scotto di Palumbo V, Piccart M, Franchi M, Zanaboni F, Lacave AJ, Fontanelli R, Favalli G, Zola P, Guastalla JP, Rosso R, Marth C, Nooij M, Presti M, Scarabelli C, Splinter TA, Ploch E, Beex LV, ten Bokkel Huinink W, Forni M, Melpignano M, Blake P, Kerbrat P, Mendiola C, Cervantes A, Goupil A, Harper PG, Madronal C, Namer M, Scarfone G, Stoot JE, Teodorovic I, Coens C, Vergote I, Vermorken JB; [[Study_Groups#EORTC|EORTC]] Gynaecological Cancer Group. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. 2003 Mar;14(3):441-8. Erratum in: Ann Oncol. 2003 May;14(5):811. [https://doi.org/10.1093/annonc/mdg112 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12598351/ PubMed]
+# '''GOG 107:''' Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2004 Oct 1;22(19):3902-8. [https://doi.org/10.1200/JCO.2004.02.088 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15459211/ PubMed]
+# '''KEYNOTE-775:''' Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. [https://doi.org/10.1056/nejmoa2108330 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35045221/ PubMed] [https://clinicaltrials.gov/study/NCT03517449 NCT03517449]
+##'''Update:''' Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. [https://doi.org/10.1200/jco.22.02152 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37058687/ PubMed]
+==Ifosfamide monotherapy {{#subobject:b078a0|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 180 mg/m<sup>2</sup> q2wk {{#subobject:175e25|Variant=1}}===
+===Regimen variant #1, 1200 mg/m<sup>2</sup> (3 days/cycle) {{#subobject:fc7107|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534840/ Shi et al. 2019 (CRC009)]
+|[https://doi.org/10.1200/jco.2006.06.4907 Homesley et al. 2007 (GOG 161)]
-|2009-2011
+|1997-2004
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#Irinotecan_.26_CMAB009_77|Irinotecan & CMAB009]]
+|[[#Ifosfamide_.26_Paclitaxel|Ifosfamide & Paclitaxel]]
-| style="background-color:#d73027" |Inferior PFS50%
+|style="background-color:#fc8d59"|Seems to have inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
+''Note: GOG 161 specifies that PO [[Mesna (Mesnex)]] is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references. This dosage is intended for patients with previous radiation.''
-====Prior treatment criteria====
-*Exposure to FOLFOX, with progression or discontinuation due to toxicity
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+*[[Ifosfamide (Ifex)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 to 3
-'''14-day cycles'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]] by the following route-based criteria:
+**IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m<sup>2</sup>)
+**PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
+'''21-day cycle for 8 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 300 mg/m<sup>2</sup> q3wk {{#subobject:190e25|Variant=1}}===
+===Regimen variant #2, 1500 mg/m<sup>2</sup> (5 days/cycle) {{#subobject:450cd5|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699713/ Seymour et al. 2013 (PICCOLO)]
+|[https://doi.org/10.1006/gyno.2000.6001 Sutton et al. 2000 (GOG 108)]
-|2006-2008
+|1989-1996
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (C)
-|[[#Irinotecan_.26_Panitumumab_99|Irinotecan & Panitumumab]]
+|[[#Cisplatin_.26_Ifosfamide_2|CIM]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.9 vs 10.4 mo<br>(HR 0.99, 95% CI 0.81-1.20)
+|style="background-color:#fc8d59"|Seems to have inferior PFS
 |-
 |}
-''Note: In some trials, this starting dose was intended for patients who were at least 70 years old, had [[Performance status|ECOG performance status]] 2 or more, or had prior pelvic radiation. Patients in N9841 had not previously received irinotecan or oxaliplatin.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*First-line fluoropyrimidine-based chemotherapy, with progression
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
-'''21-day cycles'''
+====Supportive therapy====
+*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
+'''21-day cycle for 8 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 350 mg/m<sup>2</sup> q3wk {{#subobject:627110|Variant=1}}===
+===Regimen variant #3, 1600 mg/m<sup>2</sup> (3 days/cycle) {{#subobject:5e6305|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2006.06.4907 Homesley et al. 2007 (GOG 161)]
+|1997-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Ifosfamide_.26_Paclitaxel|Ifosfamide & Paclitaxel]]
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
+|}
+''Note: GOG 161 specifies that PO [[Mesna (Mesnex)]] is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]] by the following exposure-based criteria:
+**No previous radiation: 1600 mg/m<sup>2</sup> IV once per day on days 1 to 3
+**Previous radiation: 1200 mg/m<sup>2</sup> IV once per day on days 1 to 3
+====Supportive therapy====
+*[[Mesna (Mesnex)]] by the following route-based criteria:
+**IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m<sup>2</sup>)
+**PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
+'''21-day cycle for 8 cycles'''
+</div></div>
+===References===
+# '''GOG 108:''' Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group study. Gynecol Oncol. 2000 Nov;79(2):147-53. [https://doi.org/10.1006/gyno.2000.6001 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11063636/ PubMed]
+# '''GOG 161:''' Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Feb 10;25(5):526-31. [https://doi.org/10.1200/jco.2006.06.4907 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17290061/ PubMed] [https://clinicaltrials.gov/study/NCT00003128 NCT00003128]
+==Ifosfamide & Paclitaxel {{#subobject:824258|Regimen=1}}==
+PI: '''<u>P</u>'''aclitaxel & '''<u>I</u>'''fosfamide
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:d519c4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699713/ Seymour et al. 2013 (PICCOLO)]
+|[https://doi.org/10.1200/jco.2006.06.4907 Homesley et al. 2007 (GOG 161)]
-|2006-2008
+|1997-2004
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Ifosfamide_monotherapy|Ifosfamide]]
+|style="background-color:#91cf60"|Seems to have superior OS (primary endpoint)<br>Median OS: 13.5 vs 8.4 mo<br>(HR 0.69, 95% CI 0.49-0.97)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8937015/ Powell et al. 2022 (GOG-0261)]
+|2009-2014
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Irinotecan_.26_Cyclosporine_99|Irinotecan & Cyclosporine]]<br> 2. [[#Irinotecan_.26_Panitumumab_99|Irinotecan & Panitumumab]]
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|Carboplatin & Paclitaxel]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.9 vs 10.4 mo<br>(HR 0.99, 95% CI 0.81-1.20)
+| style="background-color:#eeee01" |Non-inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
+''Note: GOG 161 specifies that PO [[Mesna (Mesnex)]] is to be taken in 3 divided doses, but only lists 2 time points for its use. The timing of the middle dose is estimated based on other references. Treatment was given for 8 cycles in GOG 161.''
-====Prior treatment criteria====
-*First-line fluoropyrimidine-based chemotherapy, with progression
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+*[[Ifosfamide (Ifex)]] by the following exposure-based criteria:
+**No previous radiation: 1600 mg/m<sup>2</sup> IV once per day on days 1 to 3
+**Previous radiation: 1200 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV over 3 hours once on day 1
 ====Supportive therapy====
-*(varied depending on reference):
+Per GOG 161:
-*"Standard regimens of [[:Category:Emesis_prevention|antiemetics]], [[Atropine (Atropen)]], and intensive [[Loperamide (Imodium)]]," but no prophylactic [[Atropine (Atropen)]] allowed on cycle 1 day 1
+*[[Mesna (Mesnex)]] by the following route-based criteria:
-'''21-day cycles'''
+**IV dosing: 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes prior to ifosfamide (total dose per cycle: 6000 mg/m<sup>2</sup>)
+**PO dosing: 1330 mg PO three times per day on days 1 to 3, taken 1 hour before, 4 hours after, and 8 hours after ifosfamide (total dose per cycle: 11,970 mg)
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 4, to continue until ANC is greater than or equal to 2000/μL
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+*One of the following H2 blockers:
+**[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+**[[Ranitidine (Zantac)]] 50 mg IV once on day 1; 30 minutes prior to paclitaxel
+'''21-day cycle for 6 to 10 cycles'''
 </div></div>
 ===References===
-#'''PICCOLO:''' Seymour MT, Brown SR, Middleton G, Maughan T, Richman S, Gwyther S, Lowe C, Seligmann JF, Wadsley J, Maisey N, Chau I, Hill M, Dawson L, Falk S, O'Callaghan A, Benstead K, Chambers P, Oliver A, Marshall H, Napp V, Quirke P. Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol. 2013 Jul;14(8):749-59. Epub 2013 May 29. [https://dx.doi.org/10.1016%2FS1470-2045(13)70163-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699713/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23725851 PubMed] NCT00389870
+# '''GOG 161:''' Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group study. J Clin Oncol. 2007 Feb 10;25(5):526-31. [https://doi.org/10.1200/jco.2006.06.4907 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17290061/ PubMed] [https://clinicaltrials.gov/study/NCT00003128 NCT00003128]
-#'''CRC009:''' Shi Y, Li J, Xu J, Sun Y, Wang L, Cheng Y, Liu W, Sun G, Chen Y, Bai L, Zhang Y, He X, Luo Y, Wang Z, Liu Y, Yao Q, Li Y, Qin S, Hu X, Bi F, Zheng R, Ouyang X. CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients: promising findings from a prospective, open-label, randomized, phase III trial. Cancer Commun (Lond). 2019 May 24;39(1):28. [https://dx.doi.org/10.1186/s40880-019-0374-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534840/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31126331 PubMed] NCT01550055
+# '''GOG-0261:''' Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Mar 20;40(9):968-977. Epub 2022 Jan 10. [https://doi.org/10.1200/jco.21.02050 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8937015/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35007153/ PubMed] [https://clinicaltrials.gov/study/NCT00954174 NCT00954174]
-==Irinotecan & Cetuximab {{#subobject:c912ee|Regimen=1}}==
+==Lenvatinib & Pembrolizumab {{#subobject:cffdf6|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b7315f|Variant=1}}===
+===Regimen {{#subobject:a27gua|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2007.13.1193 Sobrero et al. 2008 (EPIC)]
+|[https://doi.org/10.1016/S1470-2045(19)30020-8 Makker et al. 2019 (KEYNOTE-146)]
-|2003-2006
+|2015-2017
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#91cf61"|Phase 2 (RT)
-|[[Colon_cancer#Irinotecan_monotherapy_2|Irinotecan]]
+| style="background-color:#d3d3d3" |
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1056/nejmoa2108330 Makker et al. 2022 (KEYNOTE-775)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-336-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
+|Investigator's choice of:<br>1a. [[#Doxorubicin_monotherapy|Doxorubicin]]<br>1b. [[#Paclitaxel_monotherapy|Paclitaxel]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 18.3 vs 11.4 mo<br>(HR 0.62, 95% CI 0.51-0.75)
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
+''<sup>1</sup>Reported efficacy is for the overall population.''
-====Prior treatment criteria====
-*First-line fluoropyrimidine and oxaliplatin treatment, with progression or discontinuation due to toxicity
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV over 90 minutes once on day 1
-**If aged 70 years old or more, [[Performance status|ECOG performance status]] 2 or more, or prior pelvic radiation: 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
 ====Targeted therapy====
-*[[Cetuximab (Erbitux)]] as follows:
+*[[Lenvatinib (Lenvima)]] 20 mg PO once per day on days 1 to 21
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 & 15
+====Immunotherapy====
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
+*[[Pembrolizumab (Keytruda)]] as follows:
-====Supportive therapy====
+**Cycle 1 up to 35: 200 mg IV over 30 minutes once on day 1
-*[[:Category:Antihistamines|Antihistamine]] prior to at least the first infusion of [[Cetuximab (Erbitux)]]
 '''21-day cycles'''
 </div></div>
 ===References===
-<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, June 2005; the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2006; safety and efficacy results from this study were presented at the Annual Meeting of the American Association for Cancer Research, April 14-18, 2007, Los Angeles, CA; and the quality of life results from this study were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 2007. -->
+# '''KEYNOTE-146:''' Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):711-718. Epub 2019 Mar 25. [https://doi.org/10.1016/S1470-2045(19)30020-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30922731/ PubMed] [https://clinicaltrials.gov/study/NCT02501096 NCT02501096]
-#'''EPIC:''' Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 10;26(14):2311-9. Epub 2008 Apr 7. [https://doi.org/10.1200/jco.2007.13.1193 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18390971 PubMed] NCT00063141
+##'''Update:''' Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, Messing M, Stepan DE, Dutcus CE, Wu J, Schmidt EV, Orlowski R, Sachdev P, Shumaker R, Casado Herraez A. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol. 2020 Sep 10;38(26):2981-2992. Epub 2020 Mar 13. [https://doi.org/10.1200/jco.19.02627 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7479759/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32167863/ PubMed]
-=Advanced or metastatic disease, subsequent lines of therapy=
+# '''KEYNOTE-775:''' Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. [https://doi.org/10.1056/nejmoa2108330 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35045221/ PubMed] [https://clinicaltrials.gov/study/NCT03517449 NCT03517449]
-==Cetuximab monotherapy {{#subobject:a41ec2|Regimen=1}}==
+##'''Update:''' Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. [https://doi.org/10.1200/jco.22.02152 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37058687/ PubMed]
-===Example orders===
+==Paclitaxel monotherapy {{#subobject:ceedf6|Regimen=1}}==
-*[[Example orders for Cetuximab (Erbitux) in colon cancer]]
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, weekly {{#subobject:e4f241|Variant=1}}===
+===Regimen variant #1, 80 mg/m<sup>2</sup> {{#subobject:f1676a|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|<small>'''FDA-recommended dose'''</small>
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/nejmoa2108330 Makker et al. 2022 (KEYNOTE-775)]
+|2018-2020
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Lenvatinib_.26_Pembrolizumab|Lenvatinib & Pembrolizumab]]
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 175 mg/m<sup>2</sup> {{#subobject:f1656b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2004.10.182 Saltz et al. 2004]
+|[https://doi.org/10.1093/oxfordjournals.annonc.a010768 Lissoni et al. 1996]
-|2001
+|1993-1995
-| style="background-color:#91cf61" |Phase 2 (RT)
+|style="background-color:#91cf61"|Phase 2
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://doi.org/10.1056/NEJMoa033025 Cunningham et al. 2004 (BOND)]
+|[https://doi.org/10.1016/s0090-8258(02)00068-9 Lincoln et al. 2003]
-|2001-2002
+|1994-1996
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#91cf61"|Phase 2
-|[[#Irinotecan_.26_Cetuximab_2|Irinotecan & Cetuximab]]
-| style="background-color:#d73027" |Inferior TTP
-|-
-|[https://doi.org/10.1200/jco.2006.06.7595 Lenz et al. 2006 (SALVAGE)]
-|NR
-| style="background-color:#91cf61" |Phase 2
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://doi.org/10.1056/NEJMoa071834 Jonker et al. 2007 (NCIC-CTG CO.17)]
+|[https://doi.org/10.1016/j.ygyno.2015.04.026 McMeekin et al. 2015 (IXAMPLE2)]
-|2003-2005
+|2009-2012
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Colon_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
+|[[#Ixabepilone_monotherapy_999|Ixabepilone]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 6.1 vs 4.6 mo<br>(HR 0.77, 95% CI 0.64-0.92)
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
-|[https://doi.org/10.1200/JCO.2012.46.0543 Siu et al. 2013 (NCIC-CTG/AGITG CO.20)]
+|}
-|2008-2011
+''Note: in Lincoln et al. 2003, this was the dosage for patients with previous pelvic radiation.''
-| style="background-color:#1a9851" |Phase 3 (C)
+<div class="toccolours" style="background-color:#b3e2cd">
-|[[#Brivanib_.26_Cetuximab_77|Brivanib & Cetuximab]]
+====Chemotherapy====
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+====Supportive therapy====
+*[[Hydrocortisone (Cortef)]] 250 mg IV once on day 1; 60 minutes prior to paclitaxel
+*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg IM once on day 1; 60 minutes prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 60 minutes prior to paclitaxel
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 200 mg/m<sup>2</sup> {{#subobject:a2c4fa|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1016/S1470-2045(14)70118-4 Price et al. 2014 (ASPECCT)]
+|[https://doi.org/10.1016/s0090-8258(02)00068-9 Lincoln et al. 2003]
-|2010-2012
+|1994-1996
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#91cf61"|Phase 2
-|[[#Panitumumab_monotherapy|Panitumumab]]
-| style="background-color:#eeee01" |Non-inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*Saltz et al. 2004: Exposure to irinotecan-containing therapy, with clinical failure
-*BOND: Exposure to irinotecan-containing therapy, with progression
-*SALVAGE: Exposure to irinotecan, oxaliplatin, and a fluoropyrimidine
-*NCIC-CTG CO.17: Exposure to irinotecan, oxaliplatin, and a fluoropyrimidine or contraindication to these drugs
-*NCIC-CTG/AGITG CO.20: Exposure to a fluoropyrimidine and exposure to irinotecan and oxaliplatin or contraindication to these drugs
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Chemotherapy====
-*[[Cetuximab (Erbitux)]] as follows:
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
 ====Supportive therapy====
-*Varies depending on reference
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for 2 doses on day 1; 12 and 6 hours prior to paclitaxel
-*[[:Category:Antihistamines|Antihistamine]] (such as [[Diphenhydramine (Benadryl)]] 50 mg IV) prior to at least the first infusion of [[Cetuximab (Erbitux)]]
+*[[Diphenhydramine (Benadryl)]] 50 mg IV or PO once on day 1; 30 minutes prior to paclitaxel
-'''28-day cycles'''
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+'''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*Paclitaxel dose can be changed to 135 or 110 mg/m<sup>2</sup> depending on toxicity
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, bi-weekly {{#subobject:315dde|Variant=1}}===
+===Regimen variant #4, continuous infusion {{#subobject:68d2e|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 25%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1093/annonc/mdp549 Tabernero et al. 2009]
+|[https://doi.org/10.1006/gyno.1996.0227 Ball et al. 1996]
-| style="background-color:#ffffbe" |Phase 1
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
-''Note: no primary reference could be found for this exact dosing in monotherapy; in the phase I trial it is described as "the most convenient and feasible dose".''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Chemotherapy====
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Paclitaxel (Taxol)]] by the following exposure-based criteria:
-**If tolerated, subsequent doses can be given over 1 hour
+**No prior pelvic radiation: 250 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+**Previous pelvic radiation: 200 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 ====Supportive therapy====
-*[[:Category:Antihistamines|Antihistamine]] prior to [[Cetuximab (Erbitux)]]
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for 2 doses on day 1; 12 and 6 hours prior to paclitaxel
-'''14-day cycles'''
+*[[Diphenhydramine (Benadryl)]] 50 mg IV or PO once on day 1; 30 minutes prior to paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV once on day 1; 30 minutes prior to paclitaxel
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 3, 24 hours after paclitaxel, continued for at least 12 days or until two successive total leukocyte counts are 10,000 or greater, whichever comes last
+'''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*Paclitaxel dose can be changed to 200, 170, 135, 110 mg/m<sup>2</sup> depending on toxicity
 </div></div>
 ===References===
-#Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004 Apr 1;22(7):1201-8. Epub 2004 Mar 1. [https://doi.org/10.1200/JCO.2004.10.182 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14993230 PubMed]
+# Ball HG, Blessing JA, Lentz SS, Mutch DG; Gynecologic Oncology Group. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. 1996 Aug;62(2):278-81. [https://doi.org/10.1006/gyno.1996.0227 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8751561/ PubMed]
-#'''BOND:''' Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. [https://doi.org/10.1056/NEJMoa033025 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15269313 PubMed]
+# Lissoni A, Zanetta G, Losa G, Gabriele A, Parma G, Mangioni C. Phase II study of paclitaxel as salvage treatment in advanced endometrial cancer. Ann Oncol. 1996 Oct;7(8):861-3. [https://doi.org/10.1093/oxfordjournals.annonc.a010768 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8922203/ PubMed]
-#'''SALVAGE:''' Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006 Oct 20;24(30):4914-21. [https://doi.org/10.1200/jco.2006.06.7595 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17050875 PubMed]
+# Lincoln S, Blessing JA, Lee RB, Rocereto TF; Gynecologic Oncology Group. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Mar;88(3):277-81. [https://doi.org/10.1016/s0090-8258(02)00068-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12648575/ PubMed]
-<!-- # Bristol-Myers Squibb and ImClone. A Phase III Randomized Study of Cetuximab (Erbitux, C225) and Best Supportive Care Versus Best Supportive Care in Patients with Pretreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Positive Colorectal Carcinoma. Final Clinical Study Report for CA225025. 2007 Mar 5. [http://ctr.bms.com/pdf//CA225025.pdf link to original report] '''contains dosing details in manuscript''' -->
+# '''IXAMPLE2:''' McMeekin S, Dizon D, Barter J, Scambia G, Manzyuk L, Lisyanskaya A, Oaknin A, Ringuette S, Mukhopadhyay P, Rosenberg J, Vergote I. Phase III randomized trial of second-line ixabepilone versus paclitaxel or doxorubicin in women with advanced endometrial cancer. Gynecol Oncol. 2015 Jul;138(1):18-23. Epub 2015 Apr 26. [https://doi.org/10.1016/j.ygyno.2015.04.026 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25925990/ PubMed] [https://clinicaltrials.gov/study/NCT00883116 NCT00883116]
-#'''NCIC-CTG CO.17:''' Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. [https://doi.org/10.1056/NEJMoa071834 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18003960 PubMed] NCT00079066
+# '''KEYNOTE-775:''' Makker V, Colombo N, Casado Herráez A, Santin AD, Colomba E, Miller DS, Fujiwara K, Pignata S, Baron-Hay S, Ray-Coquard I, Shapira-Frommer R, Ushijima K, Sakata J, Yonemori K, Kim YM, Guerra EM, Sanli UA, McCormack MM, Smith AD, Keefe S, Bird S, Dutta L, Orlowski RJ, Lorusso D; Study 309–KEYNOTE-775 Investigators. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med. 2022 Feb 3;386(5):437-448. Epub 2022 Jan 19. [https://doi.org/10.1056/nejmoa2108330 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35045221/ PubMed] [https://clinicaltrials.gov/study/NCT03517449 NCT03517449]
-##'''Subgroup analysis:''' Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. [https://doi.org/10.1056/NEJMoa0804385 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18946061 PubMed]
+##'''Update:''' Makker V, Colombo N, Casado Herráez A, Monk BJ, Mackay H, Santin AD, Miller DS, Moore RG, Baron-Hay S, Ray-Coquard I, Ushijima K, Yonemori K, Kim YM, Guerra Alia EM, Sanli UA, Bird S, Orlowski R, McKenzie J, Okpara C, Barresi G, Lorusso D. Lenvatinib Plus Pembrolizumab in Previously Treated Advanced Endometrial Cancer: Updated Efficacy and Safety From the Randomized Phase III Study 309/KEYNOTE-775. J Clin Oncol. 2023 Jun 1;41(16):2904-2910. Epub 2023 Apr 14. [https://doi.org/10.1200/jco.22.02152 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414727/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37058687/ PubMed]
-##'''Subgroup analysis:''' Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC-CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011 Jan;22(1):118-26. Epub 2010 Jul 5. [https://doi.org/10.1093/annonc/mdq309 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20603436 PubMed]
+==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
-#'''Phase I:''' Tabernero J, Ciardiello F, Rivera F, Rodriguez-Braun E, Ramos FJ, Martinelli E, Vega-Villegas ME, Roselló S, Liebscher S, Kisker O, Macarulla T, Baselga J, Cervantes A. Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol. 2010 Jul;21(7):1537-45. Epub 2009 Nov 25. [https://doi.org/10.1093/annonc/mdp549 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19940007 PubMed]
-#'''NCIC-CTG/AGITG CO.20:''' Siu LL, Shapiro JD, Jonker DJ, Karapetis CS, Zalcberg JR, Simes J, Couture F, Moore MJ, Price TJ, Siddiqui J, Nott LM, Charpentier D, Liauw W, Sawyer MB, Jefford M, Magoski NM, Haydon A, Walters I, Ringash J, Tu D, O'Callaghan CJ. Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 Trial. J Clin Oncol. 2013 Jul 1;31(19):2477-84. Epub 2013 May 20. [https://doi.org/10.1200/JCO.2012.46.0543 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23690424 PubMed] NCT00640471
-#'''ASPECCT:''' Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014 May;15(6):569-79. Epub 2014 Apr 14. [https://doi.org/10.1016/S1470-2045(14)70118-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24739896 PubMed] NCT01001377
-##'''Update:''' Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Guan X, Peeters M. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016 Nov;68:51-59. Epub 2016 Oct 5. [https://doi.org/10.1016/j.ejca.2016.08.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27716478 PubMed]
-==Irinotecan & Cetuximab {{#subobject:5d7e80|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 125/250, irinotecan 2 weeks on, 1 week off {{#subobject:e734bb|Variant=1}}===
+===Regimen variant #1, bi-weekly {{#subobject:87f9c7|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-|<small>'''FDA-recommended dose'''</small>
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ Le et al. 2015 (KEYNOTE-016)]
+|2013-09 to 2016-09
+| style="background-color:#ffffbe" |Phase 2, fewer than 20 pts of this subtype
+|-
+|[https://doi.org/10.1200/JCO.2017.72.5952 Ott et al. 2017b (KEYNOTE-028<sub>endometrial</sub>)]
+|NR
+|style="background-color:#91cf61"|Phase 1b
 |-
 |}
-''Note: In contrast to BOND, some guidelines list irinotecan as being given on days 1 & 8 of a 21-day cycle. No primary reference could be found for this. Note also that the FDA-recommended dosing is for the cetuximab component; no comment is made about irinotecan dosing.''
+''Note: KEYNOTE-016 was an expansion to a CRC-specific trial.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Immunotherapy====
-*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8
+*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
-====Targeted therapy====
+'''14-day cycle for up to 52 cycles (2 years)'''
-*[[Cetuximab (Erbitux)]] as follows:
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 & 15
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
-====Supportive therapy====
-*[[:Category:Antihistamines|Antihistamine]] prior to at least the first infusion of [[Cetuximab (Erbitux)]]
-'''21-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 125/250, irinotecan 4 weeks on, 2 weeks off {{#subobject:a4d073|Variant=1}}===
+===Regimen variant #2, q3wk {{#subobject:87fj18|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-|<small>'''FDA-recommended dose'''</small>
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887941/ O'Malley et al. 2022 (KEYNOTE-158<sub>endometrial</sub>)]
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-!style="width: 20%"|Study
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-320-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa033025 Cunningham et al. 2004 (BOND)]
+|} -->
-|2001-2002
+|2016-2020
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|style="background-color:#91cf61"|Phase 2 (RT)
-|[[#Cetuximab_monotherapy_2|Cetuximab]]
-| style="background-color:#1a9850" |Superior TTP
 |-
 |}
-''Note that the FDA-recommended dosing is for the cetuximab component; no comment is made about irinotecan dosing.''
+''Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.''
 <div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
+====Biomarker eligibility criteria====
-*BOND: Exposure to irinotecan-containing therapy, with progression
+*Cohort K: MSI-H/dMMR endometrial cancer
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Immunotherapy====
-*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-====Targeted therapy====
+'''21-day cycle for up to 35 cycles (2 years)'''
-*[[Cetuximab (Erbitux)]] as follows:
+</div></div>
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22, 29, 36
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
+===References===
-====Supportive therapy====
+# '''KEYNOTE-028<sub>endometrial</sub>:''' Ott PA, Bang YJ, Berton-Rigaud D, Elez E, Pishvaian MJ, Rugo HS, Puzanov I, Mehnert JM, Aung KL, Lopez J, Carrigan M, Saraf S, Chen M, Soria JC. Safety and antitumor activity of pembrolizumab in advanced programmed death ligand 1-positive endometrial cancer: results from the KEYNOTE-028 study. J Clin Oncol. 2017 Aug 1;35(22):2535-2541. Epub 2017 May 10. [https://doi.org/10.1200/JCO.2017.72.5952 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28489510/ PubMed] [https://clinicaltrials.gov/study/NCT02054806 NCT02054806]
-*[[:Category:Antihistamines|Antihistamine]] prior to at least the first infusion of [[Cetuximab (Erbitux)]]
+# '''KEYNOTE-016:''' Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015 Jun 25;372(26):2509-20. Epub 2015 May 30. [https://doi.org/10.1056/NEJMoa1500596 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481136/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26028255/ PubMed] [https://clinicaltrials.gov/study/NCT01876511 NCT01876511]
-'''42-day cycles'''
+## '''Update:''' Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. Epub 2017 Jun 8. [https://doi.org/10.1126/science.aan6733 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/ link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28596308/ PubMed]
-</div></div><br>
+# '''KEYNOTE-158<sub>endometrial</sub>:''' O'Malley DM, Bariani GM, Cassier PA, Marabelle A, Hansen AR, De Jesus Acosta A, Miller WH Jr, Safra T, Italiano A, Mileshkin L, Xu L, Jin F, Norwood K, Maio M. Pembrolizumab in Patients With Microsatellite Instability-High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study. J Clin Oncol. 2022 Mar 1;40(7):752-761. Epub 2022 Jan 6. [https://doi.org/10.1200/jco.21.01874 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887941/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34990208/ PubMed] [https://clinicaltrials.gov/study/NCT02628067 NCT02628067]
+==Temsirolimus monotherapy {{#subobject:c19c6|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 150/500, bi-weekly {{#subobject:c0c538|Variant=1}}===
+===Regimen {{#subobject:53c722|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113428/ Osumi et al. 2018]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158598/ Oza et al. 2011 (NCIC IND.160)]
-|2011-2014
+|2004-2007
-| style="background-color:#91cf61" |Phase 2
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*Exposure to fluoropyrimidine‐ and oxaliplatin‐based chemotherapy, with treatment failure
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
 ====Targeted therapy====
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once on day 1
-**Subsequent doses are given over 60 minutes
+'''7-day cycles'''
-====Supportive therapy====
+</div></div>
-*[[:Category:Antihistamines|Antihistamine]] prior to [[Cetuximab (Erbitux)]]
+===References===
-'''14-day cycles'''
+# '''NCIC IND.160:''' Oza AM, Elit L, Tsao MS, Kamel-Reid S, Biagi J, Provencher DM, Gotlieb WH, Hoskins PJ, Ghatage P, Tonkin KS, Mackay HJ, Mazurka J, Sederias J, Ivy P, Dancey JE, Eisenhauer EA; NCIC Clinical Trials Group. Phase II study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J Clin Oncol. 2011 Aug 20;29(24):3278-85. Epub 2011 Jul 25. [https://doi.org/10.1200/jco.2010.34.1578 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158598/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21788564/ PubMed] [https://clinicaltrials.gov/study/NCT00072176 NCT00072176]
-</div></div><br>
+==Topotecan monotherapy {{#subobject:9a02a0|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 180/250, bi-weekly, with response adaptation {{#subobject:7c9e16|Variant=1}}===
+===Regimen {{#subobject:1c2f98|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/JCO.2011.40.9243 Van Cutsem et al. 2012 (EVEREST)]
+|[https://doi.org/10.1200/jco.2003.12.093 Wadler et al. 2003 (ECOG E3E93)]
-|2004-2005
+|1995-NR
-| style="background-color:#91cf61" |Non-randomized portion of phase 1/2 RCT
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*Exposure to irinotecan-containing chemotherapy
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 15
+*[[Topotecan (Hycamtin)]] by the following exposure-based criteria:
-====Targeted therapy====
+**No prior pelvic radiation: 1.5 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Cetuximab (Erbitux)]] 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once per day on days 8 & 15
+**Previous pelvic radiation: 1.2 mg/m<sup>2</sup> IV once per day on days 1 to 5
-'''21-day course'''
+'''21-day cycles'''
 </div>
-<div class="toccolours" style="background-color:#cbd5e7">
+<div class="toccolours" style="background-color:#fff2ae">
-====Subsequent treatment====
+====Dose and schedule modifications====
-*EVEREST, grade 0 or 1 skin reaction: Continue standard dose versus escalate dose of cetuximab to 500 mg/m<sup>2</sup>
+*Topotecan dosage for patients with previous pelvic radiation can be increased to the 1.5 mg/m<sup>2</sup> dose in later cycles if there are no toxicities higher than grade 1
-*EVEREST, grade 2 or worse skin reaction: Continue standard dose
+</div></div>
-</div></div><br>
+===References===
+# '''ECOG E3E93:''' Wadler S, Levy DE, Lincoln ST, Soori GS, Schink JC, Goldberg G. Topotecan is an active agent in the first-line treatment of metastatic or recurrent endometrial carcinoma: Eastern Cooperative Oncology Group Study E3E93. J Clin Oncol. 2003 Jun 1;21(11):2110-4. [https://doi.org/10.1200/jco.2003.12.093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12775736/ PubMed]
+=Endocrine therapy for advanced, recurrent, or metastatic disease=
+==Anastrozole monotherapy {{#subobject:534a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, 180/500, bi-weekly {{#subobject:3062ba|Variant=1}}===
+===Regimen {{#subobject:8c4e67|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527794/ Martín-Martorell et al. 2008]
+|[https://doi.org/10.1006/gyno.2000.5865 Rose et al. 2000]
-|2005-2007
+|1997-05 to 1998-03
-| style="background-color:#91cf61" |Phase 2
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
+===References===
+# Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB; Gynecologic Oncology Group. A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000 Aug;78(2):212-6. [https://doi.org/10.1006/gyno.2000.5865 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10926805/ PubMed]
+==Medroxyprogesterone acetate monotherapy {{#subobject:6c7bb9|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:8b5e67|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJM196102022640503 Kelley & Baker 1961]
+|1950-1959
+| style="background-color:#91cf61" |Non-randomized
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/jco.1999.17.6.1736 Thigpen et al. 1999]
+|1985-1989
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Medroxyprogesterone_acetate_monotherapy|MPA]]; high-dose
+|style="background-color:#ffffbf"|Did not meet primary endpoint of ORR
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Kelley & Baker 1961 examined a variety of progestins and is included for historic interest.''
-====Prior treatment criteria====
-*One previous line of chemotherapy
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Endocrine therapy====
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Medroxyprogesterone acetate (MPA)]] 200 mg PO once per day
-====Targeted therapy====
+'''Continued indefinitely'''
-*[[Cetuximab (Erbitux)]] 500 mg/m<sup>2</sup> IV over 2 hours once on day 1
+</div></div>
-**If tolerated, subsequent doses can be given over 1 hour
+===References===
-====Supportive therapy====
+# Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. [https://doi.org/10.1056/NEJM196102022640503 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13752346/ PubMed]
-*[[:Category:Antihistamines|Antihistamine]] prior to [[Cetuximab (Erbitux)]]
+# Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT; Gynecologic Oncology Group. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol. 1999 Jun;17(6):1736-44. [https://doi.org/10.1200/jco.1999.17.6.1736 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10561210/ PubMed]
-*[[Dexamethasone (Decadron)]] & [[Ondansetron (Zofran)]] prior to [[Irinotecan (Camptosar)]]
+==Medroxyprogesterone acetate & Tamoxifen {{#subobject:60584d|Regimen=1}}==
-'''14-day cycles'''
-</div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #6, 350/250, q3wk irinotecan {{#subobject:ada904|Variant=1}}===
+===Regimen {{#subobject:334b8c|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-|<small>'''FDA-recommended dose'''</small>
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/j.ygyno.2003.09.018 Whitney et al. 2004]
+|1991-06 to 1996-02
+|style="background-color:#91cf61"|Phase 2
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Medroxyprogesterone acetate (MPA)]] 100 mg PO twice per day on days 8 to 14, 22 to 28 (even-numbered weeks)
+*[[Tamoxifen (Nolvadex)]] 20 mg PO twice per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
+===References===
+# Whitney CW, Brunetto VL, Zaino RJ, Lentz SS, Sorosky J, Armstrong DK, Lee RB; Gynecologic Oncology Group. Phase II study of medroxyprogesterone acetate plus tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):4-9. [https://doi.org/10.1016/j.ygyno.2003.09.018 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14751130/ PubMed]
+==Megestrol monotherapy {{#subobject:4b50ea|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:52dc53|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa033025 Cunningham et al. 2004 (BOND)]
+|[https://doi.org/10.1056/NEJM196102022640503 Kelley & Baker 1961]
-|2001-2002
+|1950-1959
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+| style="background-color:#91cf61" |Non-randomized
-|[[#Cetuximab_monotherapy_2|Cetuximab]]
+| style="background-color:#d3d3d3" |
-| style="background-color:#1a9850" |Superior TTP
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1097/00000421-200102000-00007 Pandya et al. 2001 (ECOG E4882)]
+|1982-1984
+|style="background-color:#1a9851"|Randomized Phase 2 (C)
+|[[#Megestrol_.26_Tamoxifen|Megestrol & Tamoxifen]]
+|style="background-color:#ffffbf"|Did not meet efficacy endpoints
 |-
 |}
-''Note that the FDA-recommended dosing is for the cetuximab component; no comment is made about irinotecan dosing.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. Kelley & Baker 1961 examined a variety of progestins and is included for historic interest.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*BOND: Exposure to irinotecan-containing therapy, with progression
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Endocrine therapy====
-*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+*[[Megestrol (Megace)]] 80 mg PO twice per day
-**If aged 70 years old or more, [[Performance status|ECOG performance status]] 2 or more, or prior pelvic radiation: 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+'''Continued indefinitely'''
-====Targeted therapy====
-*[[Cetuximab (Erbitux)]] as follows:
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 & 15
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
-====Supportive therapy====
-*[[:Category:Antihistamines|Antihistamine]] prior to at least the first infusion of [[Cetuximab (Erbitux)]]
-'''21-day cycles'''
 </div></div>
 ===References===
-#'''BOND:''' Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. [https://doi.org/10.1056/NEJMoa033025 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15269313 PubMed]
+# Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. [https://doi.org/10.1056/NEJM196102022640503 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13752346/ PubMed]
-#Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008 Aug 5;99(3):455-8. [https://doi.org/10.1038/sj.bjc.6604530 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527794/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18665167 PubMed]
+# '''ECOG E4882:''' Pandya KJ, Yeap BY, Weiner LM, Krook JE, Erban JK, Schinella RA, Davis TE. Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol. 2001 Feb;24(1):43-6. [https://doi.org/10.1097/00000421-200102000-00007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11232948/ PubMed]
-#'''EVEREST:''' Van Cutsem E, Tejpar S, Vanbeckevoort D, Peeters M, Humblet Y, Gelderblom H, Vermorken JB, Viret F, Glimelius B, Gallerani E, Hendlisz A, Cats A, Moehler M, Sagaert X, Vlassak S, Schlichting M, Ciardiello F. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol. 2012 Aug 10;30(23):2861-8. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9243 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22753904 PubMed]
+==Megestrol & Tamoxifen {{#subobject:f03c30|Regimen=1}}==
-#Osumi H, Shinozaki E, Mashima T, Wakatsuki T, Suenaga M, Ichimura T, Ogura M, Ota Y, Nakayama I, Takahari D, Chin K, Miki Y, Yamaguchi K. Phase II trial of biweekly cetuximab and irinotecan as third-line therapy for pretreated KRAS exon 2 wild-type colorectal cancer. Cancer Sci. 2018 Aug;109(8):2567-2575. Epub 2018 Jul 13. [https://doi.org/full/10.1111/cas.13698 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113428/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29908105 PubMed] UMIN000019893
-==Panitumumab monotherapy {{#subobject:5a3eb5|Regimen=1}}==
-===Example orders===
-*[[Example orders for Panitumumab (Vectibix) in colon cancer]]
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:fa978e|Variant=1}}===
+===Regimen {{#subobject:4e79f7|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2006.08.1620 Van Cutsem et al. 2007 (20020408)]
+|[https://doi.org/10.1097/00000421-200102000-00007 Pandya et al. 2001 (ECOG E4882)]
-|2004-2005
+|1982-1984
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
-|[[Colon_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
+|[[#Megestrol_monotherapy|Megestrol]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 8 vs 7.3 wks<br>(HR 0.54, 95% CI 0.44-0.66)
+|style="background-color:#ffffbf"|Did not meet primary efficacy endpoints
+|-
+|[https://doi.org/10.1016/j.ygyno.2003.11.008 Fiorica et al. 2004]
+|1994-1995
+| style="background-color:#91cf61" |Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Megestrol (Megace)]] as follows:
+**Odd cycles: 80 mg PO twice per day on days 1 to 21
+*[[Tamoxifen (Nolvadex)]] as follows:
+**Even cycles: 20 mg PO twice per day on days 1 to 21
+'''21-day cycles'''
+</div></div>
+===References===
+# '''ECOG E4882:''' Pandya KJ, Yeap BY, Weiner LM, Krook JE, Erban JK, Schinella RA, Davis TE. Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol. 2001 Feb;24(1):43-6. [https://doi.org/10.1097/00000421-200102000-00007 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11232948/ PubMed]
+# Fiorica JV, Brunetto VL, Hanjani P, Lentz SS, Mannel R, Andersen W; Gynecologic Oncology Group. Phase II trial of alternating courses of megestrol acetate and tamoxifen in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Jan;92(1):10-4. [https://doi.org/10.1016/j.ygyno.2003.11.008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14751131/ PubMed]
+==Tamoxifen monotherapy {{#subobject:ab84a1|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:af71e3|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1016/S1470-2045(14)70118-4 Price et al. 2014 (ASPECCT)]
+|[https://doi.org/10.1016/0090-8258(89)90839-1 Quinn et al. 1989]
-|2010-2012
+|NR
-| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
+|style="background-color:#91cf61"|Phase 2
-|[[#Cetuximab_monotherapy_2|Cetuximab]]
-| style="background-color:#eeee01" |Non-inferior OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104888/ Kim et al. 2016 (20100007)]
+|[https://doi.org/10.1200/jco.2001.19.2.364 Thigpen et al. 2001 (GOG-81F)]
-|2011-2013
+|1987-1991
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|style="background-color:#91cf61"|Phase 2
-|[[Colon_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 10 vs 6.9 mo<br>(HR 0.72, 95% CI 0.55-0.94)
 |-
 |}
-''<sup>1</sup>Reported efficacy for 20100007 is based on the 2018 update.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Prior treatment criteria====
-*20020408 & 20100007: Exposure to irinotecan, oxaliplatin, and a fluoropyrimidine
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Endocrine therapy====
-*[[Panitumumab (Vectibix)]] 6 mg/kg IV over 60 minutes once on day 1
+*[[Tamoxifen (Nolvadex)]] 20 mg PO twice per day
-'''14-day cycles'''
+'''Continued indefinitely'''
 </div></div>
 ===References===
-<!-- Presented at the 97th Annual Meeting of the American Association for Cancer Research, April 1-5, 2006, Washington, DC; 2nd Annual Conference of the Hematology/Oncology Pharmacy Association, June 15-18, 2006, Orlando, FL; 8th Annual Conference of the World Congress on Gastrointestinal Cancer, June 28-July 1, 2006, Barcelona, Spain; and at the 31st European Society of Medical Oncology Congress, September 29-October 3, 2006, Istanbul, Turkey. -->
+# Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. 1989 Jan;32(1):1-3. [https://doi.org/10.1016/0090-8258(89)90839-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2909443/ PubMed]
-#'''20020408:''' Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64. [https://doi.org/10.1200/jco.2006.08.1620 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17470858 PubMed] NCT00113763
+# '''GOG-81F:''' Thigpen T, Brady MF, Homesley HD, Soper JT, Bell J. Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 2001 Jan 15;19(2):364-7. [https://doi.org/10.1200/jco.2001.19.2.364 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11208827/ PubMed]
-#'''ASPECCT:''' Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 2014 May;15(6):569-79. Epub 2014 Apr 14. [https://doi.org/10.1016/S1470-2045(14)70118-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24739896 PubMed] NCT01001377
+[[Category:Endometrial cancer regimens]]
-##'''Update:''' Price T, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Guan X, Peeters M. Final results and outcomes by prior bevacizumab exposure, skin toxicity, and hypomagnesaemia from ASPECCT: randomized phase 3 non-inferiority study of panitumumab versus cetuximab in chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer. Eur J Cancer. 2016 Nov;68:51-59. Epub 2016 Oct 5. [https://doi.org/10.1016/j.ejca.2016.08.010 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27716478 PubMed]
+[[Category:Disease-specific pages]]
-#'''20100007:''' Kim TW, Elme A, Kusic Z, Park JO, Udrea AA, Kim SY, Ahn JB, Valencia RV, Krishnan S, Bilic A, Manojlovic N, Dong J, Guan X, Lofton-Day C, Jung AS, Vrdoljak E. A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. Br J Cancer. 2016 Nov 8;115(10):1206-1214. Epub 2016 Oct 13. [https://doi.org/10.1038/bjc.2016.309 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104888/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27736842 PubMed] NCT01412957
+[[Category:Gynecologic cancers]]
-##'''Update:''' Kim TW, Elme A, Park JO, Udrea AA, Kim SY, Ahn JB, Valencia RV, Krishnan S, Manojlovic N, Guan X, Lofton-Day C, Jung AS, Vrdoljak E. Final Analysis of Outcomes and RAS/BRAF Status in a Randomized Phase 3 Study of Panitumumab and Best Supportive Care in Chemorefractory Wild Type KRAS Metastatic Colorectal Cancer. Clin Colorectal Cancer. 2018 Sep;17(3):206-214. Epub 2018 Mar 21. [https://www.clinical-colorectal-cancer.com/article/S1533-0028(17)30529-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29703606 PubMed]
-[[Category:Colorectal cancer regimens]]
-[[Category:Biomarker-specific pages]]
-[[Category:Gastrointestinal cancers]]

Difference between revisions of "Endometrial cancer"

Latest revision as of 00:05, 30 June 2024

Guidelines

ESMO

NCCN

Adjuvant therapy

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 5/175 x 4

Preceding treatment

Chemotherapy

Regimen variant #2, 6/175 x 6

Preceding treatment

Chemotherapy

References

Cisplatin & Doxorubicin

Regimen variant #1, 50/45, capped BSA

Preceding treatment

Chemotherapy

Supportive therapy

Regimen variant #2, 50/60 x 6

Preceding treatment

Chemotherapy

Regimen variant #3, 50/60 x 8

Preceding treatment

Chemotherapy

Supportive therapy

References

Cisplatin & Ifosfamide

Regimen

Preceding treatment

Chemotherapy

Supportive therapy

References

Cisplatin & RT

Regimen

Preceding treatment

Chemotherapy

Radiotherapy

Subsequent treatment

References

Radiation therapy

Regimen

Preceding treatment

Radiotherapy

Subsequent treatment

References

Whole abdominal radiation (WAI)

Regimen

Radiotherapy

References

Non-endocrine therapy for advanced, recurrent, or metastatic disease

Bevacizumab monotherapy

Regimen

Targeted therapy

References

Carboplatin monotherapy

Regimen variant #1, 300 mg/m2

Chemotherapy

Regimen variant #2, 400 mg/m2

Chemotherapy

References

Carboplatin & Paclitaxel (CP)

Regimen variant #1, 5/175 x 6

Chemotherapy

Regimen variant #2, 5/175 x 9

Chemotherapy

Regimen variant #3, 5/175, indefinite

Chemotherapy

Regimen variant #4, 6/175 x 6

Chemotherapy

Regimen variant #5, 6/175 x 7

Chemotherapy

Regimen variant #6, 6/175 x 6-10

Chemotherapy

Regimen variant #7, 7/175

Chemotherapy

References

Carboplatin & Paclitaxel (CP) & Dostarlimab

Regimen

Chemotherapy

Regimen variant #1, 300 mg/m²

Regimen variant #2, 400 mg/m²