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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 1: / Line 1: @@
-'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
+<span id="BackToTop"></span>
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
+[[#top|Back to Top]]
+</div>
+{{#lst:Editorial board transclusions|gyn}}
+''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!''
+{| class="wikitable" style="float:right; margin-right: 5px;"
+|-
+|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
+<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
+|}
 {{TOC limit|limit=3}}
+=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.'''
+==[https://www.esmo.org/ ESMO]==
+*'''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]
+*'''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]
+**'''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]
+**'''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]
+**'''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]
-=Hormone therapy for endometrioid histologies=
+*'''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]
-==Anastrozole (Arimidex)==
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Anastrozole (Arimidex)]] 1 mg PO once per day
+==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]
-'''given until progression of disease or unacceptable toxicity'''
+=Adjuvant therapy=
+==Carboplatin & Paclitaxel (CP) {{#subobject:b9c21f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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(18)30079-2 de Boer et al. 2018 (PORTEC-3)]
+|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)
+|[[#Cisplatin_.26_RT|Cisplatin & RT]], then [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]] x 4
+| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
+|-
+|}
+<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====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div>
+===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. [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] '''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]
+# '''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://jamanetwork.com/journals/jamaoncology/fullarticle/2728809 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, 50/45, capped BSA {{#subobject:ef532f|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/10.1016/j.ygyno.2008.11.014 Homesley et al. 2008 (GOG 184)]
+|2000-2004
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel_999|CDP]]
+|style="background-color:#ffffbf"|Did not meet primary endpoint of RFS
+|-
+|}
+''Note: Treatment was to start within 8 weeks of completion of RT.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[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====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1, '''given second'''
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1, '''given first'''
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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.2004.00.7617 Randall et al. 2006 (GOG 122)]
+|1992-2000
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|[[#Whole_abdominal_radiation_.28WAI.29|Whole abdominal irradiation]]
+|style="background-color:#1a9850"|Superior OS (secondary endpoint)<br>OS60: 55% vs 42%<br>(aHR 0.68, 95% CI 0.52-0.89)
+|-
+|}
+<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====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] as follows:
+**Cycles 1 to 7: 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 8 cycles'''
+</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 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]
+# '''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://jamanetwork.com/journals/jamaoncology/fullarticle/2728809 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 {{#subobject:f97ea4|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/PMC2752331 Wolfson et al. 2007 (GOG 150)]
+|1993-2005
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|[[#Whole_abdominal_radiation_.28WAI.29|Whole abdominal irradiation]]
+|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>Median OS is not reported in the paper and is estimated from the K-M curve.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[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'''
+*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 4, '''given second, with mesna'''
+====Supportive therapy====
+*[[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'''
+*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===
-# Rose PG, Brunetto VL, VanLe L, Bell J, Walker JL, Lee RB. 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. [http://www.sciencedirect.com/science/article/pii/S0090825800958657 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10926805 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]
+==Cisplatin & RT {{#subobject:4d8gh0|Regimen=1}}==
-==Medroxyprogesterone acetate (MPA)==
+Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen {{#subobject:4bfa1d|Variant=1}}===
-<span
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-style="background:#00CD00;
+!style="width: 20%"|Study
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Dates of enrollment
-border-color:black;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-width:2px;
+!style="width: 20%"|Comparator
-border-style:solid;">Phase III</span>
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
-*[[Medroxyprogesterone acetate (MPA)]] 200 mg PO once per day
+|[https://doi.org/10.1016/S1470-2045(18)30079-2 de Boer et al. 2018 (PORTEC-3)]
+|2006-2013
-'''given until progression of disease or unacceptable toxicity'''
+|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]]
+|-
+|}
+''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====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> 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'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*Adjuvant [[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] x 4
+</div></div>
 ===References===
-# Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT. 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. [http://jco.ascopubs.org/content/17/6/1736.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10561210 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] '''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]
+## '''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]
-==Medroxyprogesterone acetate & Tamoxifen==
+#'''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]
-===Regimen===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Medroxyprogesterone acetate (MPA)]] 100 mg PO BID on even-numbered weeks (for example, week 2, 4, 6, etc.)
-*[[Tamoxifen (Nolvadex)]] 20 mg PO BID
-'''given until progression of disease or unacceptable toxicity'''
+==Radiation therapy {{#subobject:24a846|Regimen=1}}==
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:4bfd6d|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/10.1016/j.ygyno.2003.11.048 Keys et al. 2004 (GOG 99)]
+|1987-1995
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[Endometrial_cancer_-_null_regimens#Observation|Observation]]
+| 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
+|-
+|}
+''<sup>1</sup>Reported efficacy for PORTEC-3 is based on the 2019 update.''<br>
+''Note: in PORTEC-3, radiation is to start within 4 to 6 weeks after surgery, and no later than 8 weeks.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Endometrial_cancer_surgery|Surgery]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*[[External beam radiotherapy]] to the pelvis, 4000 to 5000 cGy
+**If cervical involvement, brachytherapy boost
+'''One course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*GOG 184: Adjuvant [[#Cisplatin_.26_Doxorubicin|CD]] x 6 versus [[#CDP_999|CDP]] x 6
+</div></div>
 ===References===
-# Whitney CW, Brunetto VL, Zaino RJ, Lentz SS, Sorosky J, Armstrong DK, Lee RB; Gynecologic Oncology Group study. 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. [http://www.sciencedirect.com/science/article/pii/S0090825803006516 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14751130 PubMed]
+# '''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]
-==Megestrol acetate (Megace)==
+# '''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]
-===Regimen===
+# '''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]
-Level of Evidence:
+## '''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]
-<span
+# '''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]
-style="background:#00CD00;
+## '''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]
-padding:3px 6px 3px 6px;
+#'''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]
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II, >20 per arm</span>
-*[[Megestrol acetate (Megace)]] 80 mg PO BID
-'''given until progression of disease or unacceptable toxicity'''
+==Whole abdominal radiation (WAI) {{#subobject:37c051|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:1ab715|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.2004.00.7617 Randall et al. 2006 (GOG 122)]
+|1992-2000
+|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+|[[#Cisplatin_.26_Doxorubicin|Cisplatin & Doxorubicin]]
+|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===
-# 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. [http://journals.lww.com/amjclinicaloncology/Fulltext/2001/02000/Megestrol_and_Tamoxifen_in_Patients_With_Advanced.7.aspx link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11232948 PubMed]
+# '''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]
-==Megestrol acetate & Tamoxifen==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II, >20 per arm</span>
-*[[Megestrol acetate (Megace)]] 80 mg PO BID x 3 weeks, alternating with tamoxifen
-*[[Tamoxifen (Nolvadex)]] 20 mg PO BID x 3 weeks, alternating with megestrol
-'''3-week courses of Megestrol acetate (Megace), alternating back and forth with 3-week courses of [[Tamoxifen (Nolvadex)]]; given until progression of disease or unacceptable toxicity'''
+=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
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+'''21-day cycles'''
+</div></div>
 ===References===
-# 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. [http://journals.lww.com/amjclinicaloncology/Fulltext/2001/02000/Megestrol_and_Tamoxifen_in_Patients_With_Advanced.7.aspx link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11232948 PubMed]
+<!-- Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
-# Fiorica JV, Brunetto VL, Hanjani P, Lentz SS, Mannel R, Andersen W; Gynecologic Oncology Group study. 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. [http://www.sciencedirect.com/science/article/pii/S009082580300787X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14751131 PubMed]
+# '''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]
-==Tamoxifen (Nolvadex)==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Tamoxifen (Nolvadex)]] 20 mg PO BID
-'''given until progression of disease or unacceptable toxicity'''
+==Carboplatin monotherapy {{#subobject:f9b8ad|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 300 mg/m<sup>2</sup> {{#subobject:6a2df1|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/10.1016/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/10.1016/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%)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] 400 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+'''28-day cycles'''
+</div></div>
 ===References===
-# Quinn MA, Campbell JJ. Tamoxifen therapy in advanced/recurrent endometrial carcinoma. Gynecol Oncol. 1989 Jan;32(1):1-3. [http://www.ncbi.nlm.nih.gov/pubmed/2909443 PubMed]
+# 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]
-# 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. [http://jco.ascopubs.org/content/19/2/364.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11208827 PubMed]
-=Adjuvant radiation & chemotherapy=
-==Cisplatin, Doxorubicin, RT==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-====Adjuvant radiation====
-*Radiation therapy to the pelvis, 1.8 Gy x 28 fractions (total dose: 50.4 Gy)
-**Patients with positive para-aortic lymph nodes received 1.5 to 1.8 Gy x 24 to 29 fractions (total dose: 43.5 Gy)
-'''6-week course, begins within 8 weeks after surgery'''
+==Carboplatin & Paclitaxel (CP) {{#subobject:b0e21f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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/j.ygyno.2008.01.028 Pectasides et al. 2008]
+|2004-01 to 2007-09
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+| 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====
+*[[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 cycle for 9 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 5/175, indefinite {{#subobject:100919|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.2001.19.20.4048 Hoskins et al. 2001]
+|1995-1998
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://ijgc.bmj.com/content/18/4/803.abstract 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%"|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/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 upper limit of carboplatin dosing in DUO-E.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #5, 6/175 x 7 {{#subobject:a3c4b2|Variant=1}}===
+{| class="wikitable" style="color:black; background-color:#42f584"
+|<small>'''ESMO-preferred (I-A, 2016)'''</small>
+|-
+|}
+{| 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/PMC7676887/ Miller et al. 2020 (GOG0209)]
+|2003-2009
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel|TAP]]
+| 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)
+|-
+|}
+''Note: ESMO recommends 6 cycles, whereas the cited RCT uses 7 cycles.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV 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 7 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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/PMC8937015/ Powell et al. 2022 (GOG-0261)]
+|2009-2014
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#Ifosfamide_.26_Paclitaxel|Ifosfamide & Paclitaxel]]
+| 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)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 6 IV 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 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.2001.19.20.4048 Hoskins et al. 2001]
+|1995-1998
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+''Note: this is the upper limit of carboplatin dosing allowed in Hoskins et al. 2001.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1, given second
+*[[Carboplatin (Paraplatin)]] AUC 7 IV once on day 1, '''given second'''
-*[[Doxorubicin (Adriamycin)]] 45 mg/m2 IV once on day 1, given first
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-*Body surface area capped at 2.0 m2
+'''21-day cycles'''
+</div></div>
-'''21-day cycles x 6 cycles, to start within 8 weeks after adjuvant radiation is complete'''
-Supportive medications:
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once daily on days 2-11, or until ANC increases to 10,000; or [[Pegfilgrastim (Neulasta)]]
-*[[Dexamethasone (Decadron)]] 10 mg IV once prior to chemotherapy
-*[[antiemesis|5-HT3 antagonist]]
 ===References===
-# 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. [http://www.sciencedirect.com/science/article/pii/S0090825808009384 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19108877 PubMed]
+# 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]
+# 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://ijgc.bmj.com/content/18/4/803.abstract link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17944917/ PubMed]
-==Cisplatin, Doxorubicin, Paclitaxel, RT==
+# 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]
-===Regimen===
+# '''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://ijgc.bmj.com/content/19/4/662-664.abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/19509567/ PubMed]
-Level of Evidence:
+# '''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]
-<span
+# '''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]
-style="background:#00CD00;
+# '''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]
-padding:3px 6px 3px 6px;
+#'''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]
-border-color:black;
+#'''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]
-border-width:2px;
-border-style:solid;">Phase III</span>
-====Adjuvant radiation====
-*Radiation therapy to the pelvis, 1.8 Gy x 28 fractions (total dose: 50.4 Gy)
-**Patients with positive para-aortic lymph nodes received 1.5 to 1.8 Gy x 24 to 29 fractions (total dose: 43.5 Gy)
-'''6-week course, begins within 8 weeks after surgery'''
+==Carboplatin & Paclitaxel (CP) & Dostarlimab {{#subobject:b0e81f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:gic5c0|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/nejmoa2216334 Mirza et al. 2023 (RUBY)]
+|2019-2022
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
+| 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)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1, given second
+*[[Carboplatin (Paraplatin)]] as follows:
-*[[Doxorubicin (Adriamycin)]] 45 mg/m2 IV once on day 1, given first
+**Cycles 1 to 6: AUC 5 IV once on day 1
-*[[Paclitaxel (Taxol)]] 160 mg/m2 IV over 3 hours once on day 2
+*[[Paclitaxel (Taxol)]] as follows:
-*Body surface area capped at 2.0 m2
+**Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 1
+====Immunotherapy====
-'''21-day cycles x 6 cycles, to start within 8 weeks after adjuvant radiation is complete'''
+*[[Dostarlimab (Jemperli)]] as follows:
+**Cycles 1 to 6: 500 mg IV once on day 1
-Supportive medications:
+**Cycles 7 to 32: 1000 mg IV once on day 1
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 12, or until ANC increases to 10,000
+'''21-day cycle for 6 cycles, then 42-day cycle for up to 26 cycles (3 years)'''
-*[[Dexamethasone (Decadron)]] 10 mg IV once prior to day 1 chemotherapy; [[Dexamethasone (Decadron)]] 20 mg once 5 to 12 hours prior to paclitaxel on day 2
+</div></div>
-*[[antiemesis|5-HT3 antagonist]]
 ===References===
-# 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. [http://www.sciencedirect.com/science/article/pii/S0090825808009384 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19108877 PubMed]
+# '''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]
-=Advanced, recurrent, or metastatic disease=
-==Bevacizumab (Avastin)==
-===Regimen, Aghajanian et al. 2011===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+==Carboplatin & Paclitaxel (CP) & Durvalumab {{#subobject:bdta1f|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:duc5c0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ Westin et al. 2023 (DUO-E)]
+|rowspan=2|2020-06-02 to 2022-04-20
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
+| 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>PFS analysis of the dMMR subgroup was prespecified; FDA approval is for this subgroup.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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/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
+'''21-day cycle for 6 cycles, then 28-day cycles'''
+</div></div>
 ===References===
-# Aghajanian C, Sill MW, Darcy KM, Greer B, McMeekin DS, Rose PG, Rotmensch J, Barnes MN, Hanjani P, Leslie KK. 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. doi: 10.1200/JCO.2010.32.6397. Epub 2011 May 2. [http://jco.ascopubs.org/content/29/16/2259.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21537039 PubMed]
+#'''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 (Paraplatin)==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] 400 mg/m2 IV over 30 minutes once on day 1
-**Dosage for patients with previously treated with chemotherapy is [[Carboplatin (Paraplatin)]] 300 mg/m2 IV over 30 minutes once on day 1
-'''28-day cycles'''
+==Carboplatin & Paclitaxel (CP), Olaparib, Durvalumab {{#subobject:bdokdf|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:lod5c0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10824389/ Westin et al. 2023 (DUO-E)]
+|rowspan=2|2020-06-02 to 2022-04-20
+|rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc)
+|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
+| 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)
+|-
+|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Durvalumab|CP & Durvalumab|CP & Durvalumab]]
+| style="background-color:#d3d3d3" |Not formally compared
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====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/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====
+*[[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'''
+</div></div>
 ===References===
-# van Wijk FH, Lhommé C, Bolis G, Scotto di Palumbo V, Tumolo S, Nooij M, de Oliveira CF, Vermorken JB; European Organization for Research and Treatment of Cancer. 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. [http://www.ejcancer.info/article/S0959-8049%2802%2900504-X/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12504662 PubMed]
+#'''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 & Doxorubicin liposomal==
-===Regimen, Pignata et al. 2007 (END-1)===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, given first
-*[[Doxorubicin liposomal (Doxil)]] 40 mg/m2 IV over 60 minutes once on day 1, given second
-'''28-day cycles x 3 to 6 cycles;''' all patients received 3 cycles of therapy.  If there was no unacceptable toxicity, patients with stable or responsive disease received an additional 3 cycles.
-Supportive medications:
-*"No prophylactic use of [[Filgrastim (Neupogen)|G-CSF]] was recommended. In case of grade 4 neutropaenia, even without fever, therapeutic and prophylactic use of G-CSF was allowed."
+==Carboplatin & Paclitaxel (CP) & Pembrolizumab {{#subobject:b0bjc2|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ug1cx0|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/pmc10351614/ Eskander et al. 2023 (NRG GY018)]
+|2019-07 to 2022-12
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
+| 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)
+|-
+|}
+''<sup>1</sup>Reported efficacy is for the dMMR cohort.''<br>
+''<sup>2</sup>Reported efficacy is for the pMMR cohort.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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/m<sup>2</sup> 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'''
+</div></div>
 ===References===
-# 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359926/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17486128 PubMed]
+#'''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]
-==Carboplatin & Paclitaxel==
-===Regimen #1, Pectasides et al. 2008===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 1 hour once on day 1, given second
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1, given first
-'''21-day cycles x 6 to 9 cycles'''
-===Regimen #2, Hoskins et al. 2001 & Shechter-Maor et al. 2008===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] AUC 5 to 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'''
-===Regimen #3, Sorbe et al. 2008===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV once on day 1
+==Carboplatin & Paclitaxel (CP) & Trastuzumab {{#subobject:b0ejgf|Regimen=1}}==
+CP+T: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, '''<u>T</u>'''rastuzumab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:7ab110|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.2017.76.5966 Fader et al. 2018]
+|2011-2017
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|CP]]
+| 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====
+*HER2 overexpression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====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/m<sup>2</sup> 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'''
+</div></div>
+===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. [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]
+##'''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]
+==Carboplatin & Pegylated liposomal doxorubicin {{#subobject:c8ff00|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:d48f39|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/PMC2359926/ Pignata et al. 2007 (END-1)]
+|2002-2005
+|style="background-color:#91cf61"|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.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1, '''given first'''
+*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
+'''28-day cycle for 3 to 6 cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] were not recommended for prophylaxis, but were allowed for grade 4 neutropenia
+</div></div>
 ===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. [http://jco.ascopubs.org/content/19/20/4048.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11600606 PubMed]
+# '''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]
-# 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. [http://www.sciencedirect.com/science/article/pii/S0090825808000838 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18299146 PubMed] content property of [http://hemonc.org HemOnc.org]
-# 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. [http://www.ncbi.nlm.nih.gov/pubmed/17944917 PubMed]
-# '''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. [http://journals.lww.com/ijgc/pages/articleviewer.aspx?year=2009&issue=05000&article=00029&type=abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19509567 PubMed]
-==Cisplatin & Doxorubicin==
+==Cisplatin & Doxorubicin {{#subobject:7f9e48|Regimen=1}}==
-===Regimen #1, Fleming et al. 2004===
+AP: '''<u>A</u>'''driamycin (Doxorubicin) & '''<u>P</u>'''latinol (Cisplatin)
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Regimen variant #1, 50/45 {{#subobject:1748e2|Variant=1}}===
-style="background:#00CD00;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Study
-border-color:black;
+!style="width: 20%"|Dates of enrollment
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-style:solid;">Phase III</span>
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV over 1 hour once on day 1, given second
+|-
-*[[Doxorubicin (Adriamycin)]] 60 mg/m2 IV once on day 1, given first
+|[https://doi.org/10.1200/jco.2004.07.184 Fleming et al. 2004a (GOG 177)]
-**Dosage for patients with previous pelvic radiation or who were >65 years old is [[Doxorubicin (Adriamycin)]] 45 mg/m2 IV once on day 1
+|1998-2000
-*Body surface area capped at 2.0 m2
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin.2C_Doxorubicin.2C_Paclitaxel|Cisplatin, Doxorubicin, Paclitaxel]]
-'''21-day cycles x 7 cycles'''
+|style="background-color:#fc8d59"|Seems to have inferior OS
+|-
-===Regimen #2, Randall et al. 2006===
+|}
-Level of Evidence:
+''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.''
-<span
+<div class="toccolours" style="background-color:#b3e2cd">
-style="background:#00CD00;
+====Chemotherapy====
-padding:3px 6px 3px 6px;
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg) IV over 60 minutes once on day 1, '''given second'''
-border-color:black;
+*[[Doxorubicin (Adriamycin)]] 45 mg/m<sup>2</sup> (maximum dose of 90 mg) IV once on day 1, '''given first'''
-border-width:2px;
+'''21-day cycle for 7 cycles'''
-border-style:solid;">Phase III</span>
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV once on day 1 of cycles 1 to 8
+===Regimen variant #2, 50/60, capped BSA {{#subobject:3b1876|Variant=1}}===
-*[[Doxorubicin (Adriamycin)]] 60 mg/m2 IV once on day 1 of cycles 1 to 7
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
-'''21-day cycles x 8 cycles'''
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-Supportive hydration:
+!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 variant #4, 60/60 {{#subobject:828296|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.2003.10.083 Gallion et al. 2003 (GOG 139)]
+|1993-1996
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]; chronomodulated
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for up to 8 cycles'''
+</div></div>
 ===References===
-# 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. [http://jco.ascopubs.org/content/22/11/2159.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15169803 PubMed]
+# '''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]
-# Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group Study. 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. [http://jco.ascopubs.org/content/24/1/36.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16330675 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. [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]
+# '''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]
-==Cisplatin, Doxorubicin, Paclitaxel==
+# '''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]
-===Regimen===
+==Cisplatin, Doxorubicin, Paclitaxel {{#subobject:b61c1e|Regimen=1}}==
-Level of Evidence:
+TAP: '''<u>T</u>'''axol (Paclitaxel), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''latinol (Cisplatin)
-<span
+<br>CDP: '''<u>C</u>'''isplatin, '''<u>D</u>'''oxorubicin, '''<u>P</u>'''aclitaxel
-style="background:#00CD00;
+<div class="toccolours" style="background-color:#eeeeee">
-padding:3px 6px 3px 6px;
+===Regimen {{#subobject:68777b|Variant=1}}===
-border-color:black;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-border-width:2px;
+!style="width: 20%"|Study
-border-style:solid;">Phase III</span>
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-*[[Cisplatin (Platinol)]] 50 mg/m2 IV over 1 hour once on day 1, given second
+!style="width: 20%"|Comparator
-*[[Doxorubicin (Adriamycin)]] 45 mg/m2 IV once on day 1, given first
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-*[[Paclitaxel (Taxol)]] 160 mg/m2 IV over 3 hours once on day 2
+|-
-*Body surface area capped at 2.0 m2
+|[https://doi.org/10.1200/jco.2004.07.184 Fleming et al. 2004 (GOG 177)]
+|1998-2000
-'''21-day cycles x 7 cycles'''
+|style="background-color:#1a9851"|Phase 3 (E-esc)
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]
-Supportive medications:
+|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)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|TC]]
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|}
+''Note: in GOG 177, 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> IV over 60 minutes once on day 1, '''given second'''
+*[[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===
-# 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. [http://jco.ascopubs.org/content/22/11/2159.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15169803 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. [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]
+# '''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, Mesna (CIM)==
+==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, Wolfson et al. 2007 (GOG 150)===
+===Regimen {{#subobject:a26ea4|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-<span
+!style="width: 20%"|Study
-style="background:#00CD00;
+!style="width: 20%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+!style="width: 20%"|Comparator
-border-width:2px;
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-border-style:solid;">Phase III</span>
+|-
+|[https://doi.org/10.1006/gyno.2000.6001 Sutton et al. 2000 (GOG 108)]
-*[[Cisplatin (Platinol)]] 20 mg/m2 IV at an infusion rate of approximately 1 mg/min once per day on days 1 to 4, given first
+|1989-1996
-*[[Ifosfamide (Ifex)]] 1500 mg/m2 IV over 1 hour once per day on days 1 to 4, given second together with mesna
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-*[[Mesna (Mesnex)]] 120 mg/m2 IV bolus over 15 minutes once on day 1;, then [[Mesna (Mesnex)]] 1500 mg/m2/day IV continuous infusion over 96 hours on days 1 to 4, given second together with ifosfamide
+|[[#Ifosfamide_monotherapy|Ifosfamide]]
+| style="background-color:#91cf60" |Seems to have superior PFS (co-primary endpoint)
-'''21-day cycles x 3 cycles'''
+|-
+|}
-Supportive medications:
+<div class="toccolours" style="background-color:#b3e2cd">
-*Suggested hydration: 1 liter of NS or 1/2 NS given over several hours prior to chemotherapy
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*[[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===
-# 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752331 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17822748 PubMed]
+# '''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}}==
-==Cisplatin & Paclitaxel==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen===
+===Regimen {{#subobject:b3c8fd|Variant=1}}===
-Level of Evidence:
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-<span
+!style="width: 33%"|Study
-style="background:#EEEE00;
+!style="width: 33%"|Dates of enrollment
-padding:3px 6px 3px 6px;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-color:black;
+|-
-border-width:2px;
+|[https://doi.org/10.1006/gyno.2000.5827 Dimopoulos et al. 2000]
-border-style:solid;">Phase II</span>
+|1995-06 to 1997-05
+|style="background-color:#91cf61"|Phase 2
-*[[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
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
-'''21-day cycles x up to 6 cycles'''
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
-Supportive medications:
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-*[[Dexamethasone (Decadron)]] 20 mg PO/IV given twice, 12 and 6 hours prior to paclitaxel
+====Supportive therapy====
-*Diphenhydramine (Benadryl) 25 mg IV once 30 minutes prior to paclitaxel
+*[[Dexamethasone (Decadron)]] 20 mg IV or PO for two doses on day 1; 12 and 6 hours prior to paclitaxel
-*Ranitidine (Zantac) 50 mg IV once 30 minutes 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 [[antiemesis|antiemetics]]"
+*"Appropriate antiemetics"
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 5 and continuing until WBC >10,000
+*[[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. [http://www.sciencedirect.com/science/article/pii/S009082580095827X link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10873410 PubMed]
+# 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 (Cosmegen)==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-*[[Dactinomycin (Cosmegen)]] 2 mg/m2 IV over 15 minutes once on day 1
+==Dactinomycin monotherapy {{#subobject:97a01a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:2019ab|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.1999.5652 Moore et al. 1999]
+|1996
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Dactinomycin (Cosmegen)]] 2 mg/m<sup>2</sup> IV over 15 minutes once on day 1
 '''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">
+====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'''
+</div></div>
 ===References===
-# Moore DH, Blessing JA, Dunton C, Buller RE, Reid GC. 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. [http://www.sciencedirect.com/science/article/pii/S0090825899956524 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10600310 PubMed]
+#'''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]
+##'''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]
-==Ifosfamide==
+##'''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]
-===Regimen===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''Note: Homesley et al. 2007 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.''
-*[[Ifosfamide (Ifex)]] 1600 mg/m2 IV once per day on days 1 to 3
-**Dosage for patients with previous radiation is [[Ifosfamide (Ifex)]] 1200 mg/m2 IV once per day on days 1 to 3
-*[[Mesna (Mesnex)]] 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes before ifosfamide
-**Alternate PO dosing: [[Mesna (Mesnex)]] 1330 mg PO taken three times per day, 1 hour before, 4 hours after, and 8 hours after ifosfamide (4000 mg total dose per day), on days 1 to 3
-'''21-day cycles x 8 cycles'''
-Supportive medications:
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day starting on day 4, to continue until ANC is greater than or equal to 2000
+==Doxorubicin monotherapy {{#subobject:e5b103|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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/mdg112 Aapro et al. 2003 (EORTC 55872)]
+|1988-1994
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Doxorubicin_2|Cisplatin & Doxorubicin]]
+| style="background-color:#fee08b" |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.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1
+'''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====
+*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+'''21-day cycle for up to 8 cycles'''
+</div></div>
+===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. [https://pubmed.ncbi.nlm.nih.gov/369691/ 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]
+# '''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]
+# '''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]
+# '''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, 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%"|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. This dosage is intended for patients with previous radiation.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]] 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><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===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%"|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/10.1006/gyno.2000.6001 Sutton et al. 2000 (GOG 108)]
+|1989-1996
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Cisplatin_.26_Ifosfamide_2|CIM]]
+|style="background-color:#fc8d59"|Seems to have inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
+====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, 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%"|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 (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)
+|[[#Carboplatin_.26_Paclitaxel_.28CP.29_2|Carboplatin & Paclitaxel]]
+| style="background-color:#eeee01" |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.''
+<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
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> 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/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===
-# 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. [http://jco.ascopubs.org/content/25/5/526.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17290061 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]
+# '''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]
-==Ifosfamide & Paclitaxel==
+==Lenvatinib & Pembrolizumab {{#subobject:cffdf6|Regimen=1}}==
-===Regimen===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen {{#subobject:a27gua|Variant=1}}===
-<span
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-style="background:#00CD00;
+!style="width: 20%"|Study
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Dates of enrollment
-border-color:black;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-width:2px;
+!style="width: 20%"|Comparator
-border-style:solid;">Phase III</span>
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
-''Note: Homesley et al. 2007 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.''
+|[https://doi.org/10.1016/S1470-2045(19)30020-8 Makker et al. 2019 (KEYNOTE-146)]
-*[[Ifosfamide (Ifex)]] 1600 mg/m2 IV once per day on days 1 to 3
+|2015-2017
-**Dosage for patients with previous radiation is [[Ifosfamide (Ifex)]] 1200 mg/m2 IV once per day on days 1 to 3
+|style="background-color:#91cf61"|Phase 2 (RT)
-*[[Mesna (Mesnex)]] 2000 mg IV over 12 hours once per day on days 1 to 3, starting 15 minutes before ifosfamide
+| style="background-color:#d3d3d3" |
-**Alternate PO dosing: [[Mesna (Mesnex)]] 1330 mg PO taken three times per day, 1 hour before, 4 hours after, and 8 hours after ifosfamide (4000 mg total dose per day), on days 1 to 3
+| style="background-color:#d3d3d3" |
-*[[Paclitaxel (Taxol)]] 135 mg/m2 IV over 3 hours once on day 1
+|-
+|[https://doi.org/10.1056/nejmoa2108330 Makker et al. 2022 (KEYNOTE-775)]
-'''21-day cycles x 8 cycles'''
+<!-- {| 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>]'''
-Supportive medications:
+|-
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day starting on day 4, to continue until ANC is greater than or equal to 2000
+|} -->
-*[[Dexamethasone (Decadron)]] 20 mg PO/IV given twice, 12 and 6 hours prior to paclitaxel
+|2018-2020
-*Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to paclitaxel
+|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
-*Cimetidine (Tagamet) 300 mg IV or Ranitidine (Zantac) 50 mg IV once 30 minutes prior to paclitaxel
+|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)
+|-
+|}
+''<sup>1</sup>Reported efficacy is for the overall population.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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'''
+</div></div>
 ===References===
-# 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. [http://jco.ascopubs.org/content/25/5/526.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17290061 PubMed]
+# '''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]
+##'''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]
-==Paclitaxel (Taxol)==
+# '''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]
-===Regimen #1, Lincoln et al. 2003===
+##'''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]
-Level of Evidence:
+==Paclitaxel monotherapy {{#subobject:ceedf6|Regimen=1}}==
-<span
+<div class="toccolours" style="background-color:#eeeeee">
-style="background:#EEEE00;
+===Regimen variant #1, 80 mg/m<sup>2</sup> {{#subobject:f1676a|Variant=1}}===
-padding:3px 6px 3px 6px;
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-border-color:black;
+!style="width: 20%"|Study
-border-width:2px;
+!style="width: 20%"|Dates of enrollment
-border-style:solid;">Phase II</span>
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
-*[[Paclitaxel (Taxol)]] 200 mg/m2 IV over 3 hours once on day 1
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-**Dosage for patients with previous pelvic radiation is [[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+|-
-**Dose of [[Paclitaxel (Taxol)]] can be changed to 135 or 110 mg/m2 depending on toxicity
+|[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%"|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/oxfordjournals.annonc.a010768 Lissoni et al. 1996]
+|1993-1995
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1016/s0090-8258(02)00068-9 Lincoln et al. 2003]
+|1994-1996
+|style="background-color:#91cf61"|Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1016/j.ygyno.2015.04.026 McMeekin et al. 2015 (IXAMPLE2)]
+|2009-2012
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Ixabepilone_monotherapy_999|Ixabepilone]]
+| style="background-color:#91cf60" |Seems to have superior OS
+|-
+|}
+''Note: in Lincoln et al. 2003, this was the dosage for patients with previous pelvic radiation.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[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/s0090-8258(02)00068-9 Lincoln et al. 2003]
+|1994-1996
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> 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'''
+</div>
-Supportive medications:
+<div class="toccolours" style="background-color:#fff2ae">
-*[[Dexamethasone (Decadron)]] 20 mg PO/IV given twice, 12 and 6 hours prior to paclitaxel
+====Dose and schedule modifications====
-*Diphenhydramine (Benadryl) 50 mg PO/IV once 30 minutes prior to paclitaxel
+*Paclitaxel dose can be changed to 135 or 110 mg/m<sup>2</sup> depending on toxicity
-*Cimetidine (Tagamet) 300 mg IV once 30 minutes prior to paclitaxel
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen #2, Lissoni et al. 1996===
+===Regimen variant #4, continuous infusion {{#subobject:68d2e|Variant=1}}===
-Level of Evidence:
+{| class="wikitable" style="width: 40%; text-align:center;"
-<span
+!style="width: 25%"|Study
-style="background:#EEEE00;
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-padding:3px 6px 3px 6px;
+|-
-border-color:black;
+|[https://doi.org/10.1006/gyno.1996.0227 Ball et al. 1996]
-border-width:2px;
+|style="background-color:#91cf61"|Phase 2
-border-style:solid;">Phase II</span>
+|-
+|}
-*[[Paclitaxel (Taxol)]] 175 mg/m2 IV over 3 hours once on day 1
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] by the following exposure-based criteria:
+**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====
+*[[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'''
+</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===
+# 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]
+# 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]
+# 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]
+# '''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]
+# '''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]
+==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, bi-weekly {{#subobject:87f9c7|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/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: KEYNOTE-016 was an expansion to a CRC-specific trial.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
+'''14-day cycle for up to 52 cycles (2 years)'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, q3wk {{#subobject:87fj18|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/PMC8887941/ O'Malley et al. 2022 (KEYNOTE-158<sub>endometrial</sub>)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-320-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|2016-2020
+|style="background-color:#91cf61"|Phase 2 (RT)
+|-
+|}
+''Note: KEYNOTE-158 was a basket study with multiple arms of different enrollment periods.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+*Cohort K: MSI-H/dMMR endometrial cancer
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
-Supportive medications:
+===References===
-*Hydrocortisone (Cortef) 250 mg IV once 1 hour prior to paclitaxel
+# '''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]
-*Chlorphenamine/chlorpheniramine (H1 blocker) 10 mg IM once 1 hour prior to paclitaxel
+# '''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]
-*Cimetidine (Tagamet) 300 mg IV once 1 hour prior to paclitaxel
+## '''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. [http://science.sciencemag.org/content/357/6349/409.long 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]
+# '''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]
-===Regimen #3, Ball et al. 1996===
+==Temsirolimus monotherapy {{#subobject:c19c6|Regimen=1}}==
-Level of Evidence:
+<div class="toccolours" style="background-color:#eeeeee">
-<span
+===Regimen {{#subobject:53c722|Variant=1}}===
-style="background:#EEEE00;
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-padding:3px 6px 3px 6px;
+!style="width: 33%"|Study
-border-color:black;
+!style="width: 33%"|Dates of enrollment
-border-width:2px;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-style:solid;">Phase II</span>
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3158598/ Oza et al. 2011 (NCIC IND.160)]
-*[[Paclitaxel (Taxol)]] 250 mg/m2 IV continuous infusion over 24 hours once on day 1
+|2004-2007
-**Dosage for patients with previous pelvic radiation is [[Paclitaxel (Taxol)]] 200 mg/m2 IV continuous infusion over 24 hours once on day 1
+|style="background-color:#91cf61"|Phase 2
-**Dose of [[Paclitaxel (Taxol)]] can be changed to 200, 170, 135, 110 mg/m2 depending on toxicity
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once on day 1
+'''7-day cycles'''
+</div></div>
+===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. [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]
+==Topotecan monotherapy {{#subobject:9a02a0|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:1c2f98|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.2003.12.093 Wadler et al. 2003 (ECOG E3E93)]
+|1995-NR
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Topotecan (Hycamtin)]] by the following exposure-based criteria:
+**No prior pelvic radiation: 1.5 mg/m<sup>2</sup> IV once per day on days 1 to 5
+**Previous pelvic radiation: 1.2 mg/m<sup>2</sup> IV once per day on days 1 to 5
 '''21-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*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
+</div></div>
+===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]
-Supportive medications:
+=Endocrine therapy for advanced, recurrent, or metastatic disease=
-*[[Dexamethasone (Decadron)]] 20 mg PO/IV given twice, 12 and 6 hours prior to paclitaxel
+==Anastrozole monotherapy {{#subobject:534a|Regimen=1}}==
-*Diphenhydramine (Benadryl) 50 mg PO/IV once 30 minutes prior to paclitaxel
+<div class="toccolours" style="background-color:#eeeeee">
-*Cimetidine (Tagamet) 300 mg IV once 30 minutes prior to paclitaxel
+===Regimen {{#subobject:8c4e67|Variant=1}}===
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day starting on day 3, 24 hours after chemotherapy, continued for at least 12 days or until two successive total leukocyte counts are 10,000 or greater, whichever comes last
+{| 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.2000.5865 Rose et al. 2000]
+|1997-05 to 1998-03
+|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
+|-
+|}
+''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:#b3e2cd">
+====Endocrine therapy====
+*[[Medroxyprogesterone acetate (MPA)]] 200 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
 ===References===
-# Ball HG, Blessing JA, Lentz SS, Mutch DG. 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. [http://www.sciencedirect.com/science/article/pii/S0090825896902279 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8751561 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]
-# 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. [http://annonc.oxfordjournals.org/content/7/8/861.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8922203 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. [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]
-# Lincoln S, Blessing JA, Lee RB, Rocereto TF. Activity of paclitaxel as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2003 Mar;88(3):277-81. [http://www.sciencedirect.com/science/article/pii/S0090825802000689 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12648575 PubMed]
+==Medroxyprogesterone acetate & Tamoxifen {{#subobject:60584d|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Temsirolimus (Torisel)==
+===Regimen {{#subobject:334b8c|Variant=1}}===
-===Regimen, Oza et al. 2011===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-Level of Evidence:
+!style="width: 33%"|Study
-<span
+!style="width: 33%"|Dates of enrollment
-style="background:#EEEE00;
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-padding:3px 6px 3px 6px;
+|-
-border-color:black;
+|[https://doi.org/10.1016/j.ygyno.2003.09.018 Whitney et al. 2004]
-border-width:2px;
+|1991-06 to 1996-02
-border-style:solid;">Phase II</span>
+|style="background-color:#91cf61"|Phase 2
+|-
-*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
-'''28-day cycles, given until progression of disease, unacceptable toxicity, or patient decision'''
+====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%"|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" |
+|-
+|[http://journals.lww.com/amjclinicaloncology/Fulltext/2001/02000/Megestrol_and_Tamoxifen_in_Patients_With_Advanced.7.aspx 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: 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:#b3e2cd">
+====Endocrine therapy====
+*[[Megestrol (Megace)]] 80 mg PO twice per day
+'''Continued indefinitely'''
+</div></div>
 ===References===
-# 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. 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. doi: 10.1200/JCO.2010.34.1578. Epub 2011 Jul 25. [http://jco.ascopubs.org/content/29/24/3278.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21788564 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]
+# '''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. [http://journals.lww.com/amjclinicaloncology/Fulltext/2001/02000/Megestrol_and_Tamoxifen_in_Patients_With_Advanced.7.aspx link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11232948/ PubMed]
-==Topotecan (Hycamtin)==
+==Megestrol & Tamoxifen {{#subobject:f03c30|Regimen=1}}==
-===Regimen===
+<div class="toccolours" style="background-color:#eeeeee">
-Level of Evidence:
+===Regimen {{#subobject:4e79f7|Variant=1}}===
-<span
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-style="background:#EEEE00;
+!style="width: 20%"|Study
-padding:3px 6px 3px 6px;
+!style="width: 20%"|Dates of enrollment
-border-color:black;
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-border-width:2px;
+!style="width: 20%"|Comparator
-border-style:solid;">Phase II</span>
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
-*[[Topotecan (Hycamtin)]] 1.5 mg/m2 IV once per day on days 1 to 5
+|[http://journals.lww.com/amjclinicaloncology/Fulltext/2001/02000/Megestrol_and_Tamoxifen_in_Patients_With_Advanced.7.aspx Pandya et al. 2001 (ECOG E4882)]
-**Dosage for patients with previous pelvic radiation is [[Topotecan (Hycamtin)]] 1.2 mg/m2, which can be increase to the 1.5 mg/m2 dose in later cycles if there are no toxicities higher than grade 1
+|1982-1984
+|style="background-color:#1a9851"|Randomized Phase 2 (E-switch-ic)
+|[[#Megestrol_monotherapy|Megestrol]]
+|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===
-# 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. [http://jco.ascopubs.org/content/21/11/2110.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12775736 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. [http://journals.lww.com/amjclinicaloncology/Fulltext/2001/02000/Megestrol_and_Tamoxifen_in_Patients_With_Advanced.7.aspx 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]
-==Whole abdominal radiation (WAI)==
-===Regimen===
-Level of Evidence:
-<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-''Not commonly used but was a comparator arm; here for reference purposes only.''
+==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/10.1016/0090-8258(89)90839-1 Quinn et al. 1989]
+|NR
+|style="background-color:#91cf61"|Phase 2
+|-
+|[https://doi.org/10.1200/jco.2001.19.2.364 Thigpen et al. 2001 (GOG-81F)]
+|1987-1991
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Tamoxifen (Nolvadex)]] 20 mg PO twice per day
+'''Continued indefinitely'''
+</div></div>
 ===References===
-# Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group Study. 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. [http://jco.ascopubs.org/content/24/1/36.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16330675 PubMed]
+# 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]
-# 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752331 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17822748 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. [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]
+[[Category:Endometrial cancer regimens]]
+[[Category:Disease-specific pages]]
+[[Category:Gynecologic cancers]]

Difference between revisions of "Endometrial cancer"

Revision as of 19:30, 23 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