Uterine Sarcoma Treatment Regimens

Uterine Sarcoma Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.


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These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The National Comprehensive Cancer Network Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Systemic Therapy for Uterine Sarcoma1

REGIMEN

DOSING

Adjuvant Chemotherapy for High-Risk Disease or Primary Therapy for Initially Unresectable Diseasea

Preferred Regimens

Docetaxel + Gemcitabine2,3

Days 1,8: Gemcitabine 900mg/m2 IV at a rate of 10mg/m2/minute, followed by:

Day 8: Docetaxel 75-100mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1,8: Gemcitabine 675mg/m2 (if prior pelvic radiation) IV at a rate of 10mg/m2/minute, followed by:

Day 8: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Doxorubicin4

Day 1: Doxorubicin 60-75mg/m2 IV push.

Repeat cycle every 3 weeks for 4-6 cycles.

Other Recommended Regimens

Dacarbazine5,6

Days 1-5: Dacarbazine 250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1-5: Dacarbazine 187mg/m2 (if prior pelvic radiation) IV over 30 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Day 1: Dacarbazine 1,000mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks for 4-6 cycles.

Doxorubicin + Decarbazine7,8

Days 1-4: Doxorubicin 15mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Dacarbazine 187.5-250mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 3 weeks for 4-6 cycles.

Doxorubicin + Ifosfamide9,10,b

Days 1-3: Doxorubicin 25mg/m2 IV push

Days 1-3: Ifosfamide 3,000mg/m2 IV continuous infusion over 24 hours daily

Days 1-3: Mesna 3,000mg/m2 IV continuous infusion over 24 hours concurrently with Ifosfamide (additional Mesna may be administered following the completion of Ifosfamide per institutional standard).

Repeat cycle every 3 weeks for 4-6 cycles.

Epirubicin11

Day 1: Epirubicin 75mg/m2 IV push.

Repeat cycle every 3 weeks for 4-6 cycles.

Gemcitabine12

Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks for 4-6 cycles.

Gemcitabine + Dacarbazine13

Day 1: Gemcitabine 1,800mg/m2 IV at a rate of 10mg/m2/minute

Day 1: Dacarbazine 500mg/m2 IV over 60 minutes.

Repeat cycle every 2 weeks for 4-6 cycles.

Gemcitabine + Vinorelbine14

Days 1,8: Vinorelbine 25mg/m2 IV over 5-10 minutes

Days 1,8: Gemcitabine 800mg/m2 IV at a rate of 10mg/m2/minute.

Repeat cycle every 3 weeks for 4-6 cycles.

Ifosfamide15,16,b

Days 1-5: Ifosfamide 1,500mg/m2 IV over 3 hours

Days 1-5: Mesna 300mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose.

Repeat cycle every 3 weeks for 4-6 cycles.

OR

Days 1-3: Ifosfamide 3,000mg/m2 IV continuous infusion over 24 hours daily

Days 1-3: Mesna 3,000mg/m2 IV continuous infusion over 24 hours concurrently with Ifosfamide (addition Mesna may be administered following the completion of Ifosfamide per institutional standard).

Repeat cycle every 3 weeks for 4-6 cycles.

Liposomal Doxorubicin17,18

Day 1: Liposomal Doxorubicin 50mg/m2 IV.

Repeat cycle every 4 weeks for 4-6 cycles.

Systemic Therapy for Recurrent or Metastatic Diseasea

Preferred Regimens

Chemotherapy

Docetaxel + Gemcitabine2,3

Days 1,8: Gemcitabine 900mg/m2 IV at a rate of 10mg/m2/minute, followed by:

Day 8: Docetaxel 75-100mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

OR

Days 1,8: Gemcitabine 675mg/m2 (if prior pelvic radiation) IV at a rate of 10mg/m2/minute, followed by:

Day 8: Docetaxel 75mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Doxorubicin4

Day 1: Doxorubicin 60-75mg/m2 IV push.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Other Recommended Regimens

Chemotherapy

Dacarbazine5,6

Days 1-5: Dacarbazine 250mg/m2 IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Days 1-5: Dacarbazine 187mg/m2 (if prior pelvic radiation) IV over 30 minutes.

Repeat cycle every 3 weeks.

OR

Day 1: Dacarbazine 1,000mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks.

Doxorubicin + Decarbazine7,8

Days 1-4: Doxorubicin 15mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Dacarbazine 187.5-250mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Doxorubicin + Ifosfamide9,10,b

Days 1-3: Doxorubicin 25mg/m2 IV push

Days 1-3: Ifosfamide 3,000mg/m2 IV continuous infusion over 24 hours daily

Days 1-3: Mesna 3,000mg/m2 IV continuous infusion over 24 hours concurrently with Ifosfamide (additional Mesna may be administered following the completion of Ifosfamide per institutional standard).

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Epirubicin11

Day 1: Epirubicin 75mg/m2 IV push.

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Gemcitabine12

Days 1,8,15: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks.

Gemcitabine + Dacarbazine13

Day 1: Gemcitabine 1,800mg/m2 IV at a rate of 10mg/m2/minute

Day 1: Dacarbazine 500mg/m2 IV over 60 minutes.

Repeat cycle every 2 weeks.

Gemcitabine + Vinorelbine14

Days 1,8: Vinorelbine 25mg/m2 IV over 5-10 minutes

Days 1,8: Gemcitabine 800mg/m2 IV at a rate of 10mg/m2/minute.

Repeat cycle every 3 weeks.

Ifosfamide15,16,b

Days 1-5: Ifosfamide 1,500mg/m2 IV over 3 hours

Days 1-5: Mesna 300mg/m2 IV over 15 minutes before Ifosfamide, then at 4 and 8 hours from the start of each Ifosfamide dose.

Repeat cycle every 3 weeks.

OR

Days 1-3: Ifosfamide 3,000mg/m2 IV continuous infusion over 24 hours daily

Days 1-3: Mesna 3,000mg/m2 IV continuous infusion over 24 hours concurrently with Ifosfamide (addition Mesna may be administered following the completion of Ifosfamide per institutional standard).

Repeat cycle every 3 weeks.

Liposomal Doxorubicin17,18

Day 1: Liposomal Doxorubicin 50mg/m2 IV.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Trabectedin (for patients with uterine leiomyosarcoma treated with a prior anthracycline- containing regimen)6

Day 1: Trabectedin 1.5mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 3 weeks.

Subsequent Systemic Therapy for Recurrent or Metastatic Diseasea,c

Chemotherapy

Eribulin (Category 2B)19,20

Days 1,8: Eribulin 1.4mg/m2 IV push.

Repeat cycle every 3 weeks.

Temozolomide21,22

Days 1-5: Temozolomide 150-300mg/m2 orally.

Repeat cycle every 4 weeks.

OR

Days 1-42: Temozolomide 75-100mg/m2 orally.

Repeat cycle every 56 days.

Targeted Therapy

Pazopanib23,24

Days 1-28: Pazopanib 800mg orally.

Repeat cycle every 4 weeks.

Hormone Therapy for Low-Grade Endometrial Stromal Sarcoma or Hormone Receptor-Positive (ER and/or PR) Uterine Leiomyosarcoma

Preferred Regimens for Low-Grade Endometrial Stromal Sarcomad

Anastrozole25

See NCCN Uterine Neoplasms Guidelines1

Exemestane26

Letrozle27

Other Recommended Regimens for Low-Grade Endometrial Stromal Sarcomad

Fulvestrant28

See NCCN Uterine Neoplasms Guidelines1

GnRH Analogs (Category 2B)

Megestrol Acetate

Medroxyprogesterone Acetate

Other Recommended Regimens for ER and/or PR-Positive Uterine Leiomyosarcomae

Anastrozole25

See NCCN Uterine Neoplasms Guidelinese

Exemestane26

Fulvestrant28

GnRH Analogs (Category 2B)

Letrozle27

Megestrol Acetate (Category 2B)

Medroxyprogesterone Acetate (Category 2B)

 a.  See section on hormone therapy for patients with low-grade endometrial stromal sarcoma or hormone receptor-positive uterine leiomyosarcoma.

 b. Hydration is required pre- and postadministration of Ifosfamide.

 c. Pazopanib, temzolomide, and eribulin may be considered for use in patients with recurrent or metastatic disease who have progressed on prior cytotoxic chemotherapy.

 d. For low-grade endometrial stromal sarcoma, the first choice of systemic therapy is estrogen blockade.

 e. These hormonal therapies may be considered for patients with uterine leiomyosarcoma that is ER/PR-positive, preferably with small tumor volume or an indolent growth pace.

References

   1.  Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™, Uterine Neoplasms. V5.2019. https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. Accessed February 7, 2020.

   2.  Hensley ML, Miller A, O’Malley DM, et al. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study. J Clin Oncol. 2015;33:1180-1185.

   3.  Pautier P, Floquet A, Penel N, et al, Randomized multicenter and stratified phase II study of gemcitabine alone versus gemcitabine and docetaxel in patients with metastatic or relapsed leiomyosarcomas: A Federation Nationale Des Centres De Lutte Contre Le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM Study). Oncologist. 2012;1213-1220.

   4.  Santoro A, Tursz T, Mouridsen H, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: A randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995;13:1537-1545.

   5.  Omura GA, Major FJ, Blessing JA, et al. Randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Cancer. 1983;52:626-632.

   6.  Demetri GD, von Mehren M, Jones RL, et al. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: Results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016;34:786-793.

   7.  Antman K, Crowley J, Balcerzak SP, et al. An Intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993;11:1276-1285.

   8.  Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: A Southwest Oncology Group Study. J Natl Cancer Inst. 1991;83:926-932.

   9.  Edmonson JH, Ryan LM, Blum RH, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993;11:1269-1275.

 10.  Grobmyer SR, Maki RG, Demetri GD, et al. Neo-adjuvant chemotherapy for primary high-grade extremity soft tissue sarcoma. Ann Oncol. 2004;15:1667-1672.

 11.  Nielsen OS, Dombernowsky P, Mouriden H, et al. Epirubicin is not superior to doxorubicin in the treatment of advanced soft tissue sarcomas.The experience of the EORTC Soft Tissue and Bone Sarcoma Group. Sarcoma. 2000;4:31-35.

 12.  Look KY, Sandler A, Blessing JA, et al. Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: A Gynecologic Oncology Group (GOG) Study. Gynecol Oncol. 2004;92:644-647.

 13.  Garcia-Del-Muro X, Lopez-Pousa A, Maurel J, et al. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: A Spanish Group for Research on Sarcomas Study. J Clin Oncol. 2011;29:2528-2533.

 14.  Dileo P, Morgan JA, Zahrieh D, et al. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: Results of a phase II trial. Cancer. 2007;109:1863-1869.

 15.  Sutton G, Brunetto VL, Kilgore L, et al. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol. 2000;79:147-153.

 16.  Van Oosterom AT, Mouridsen HT, Nielsen OS, et al. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002;38:2397-2406.

 17.  Judson I, Radford JA, Harris M, et al. Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: A study by the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. 2001;37:870-877.

 18.  Sutton G, Blessing J, Hanjani P, et al. Phase II evaluation of liposomal doxorubicin (Doxil) in recurrent or advanced leiomyosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol. 2005;96:749-752.

 19.  Schoffski P, Ray-Coquard I, Cioffi A, et al. Activity of eribulin mesylate in patients with soft-tissue sarcoma: A phase 2 study in four independent histological subtypes. Lancet Oncol. 2011;12:1045-1052.

 20.  Schoffski P, Maki RG, Italiano A, et al. Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI). J Clin Oncol. 2017;33(18_suppl): Abstract 10502.

 21.  Anderson S, Aghajanian C. Temozolomide in uterine leiomyosarcomas. Gynecol Oncol. 2005;98:99-103.

 22.  Garcia del Muro X, Lopez-Pousa A, Martin J, et al. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: A Study by the Spanish Group for Research on Sarcomas. Cancer. 2005;104:1706-1712.

 23.  Van der Graaf WTA, Blay J-Y, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012;379:1879-1886.

 24.  Pazopanib (Votrient) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals, Corp.;2017. .

 25.  Anastrozole (Arimidex_ [package insert]. Baudette, MN: ANI Pharmaceuticals, Inc.; 2018.

26.  Exemestane (Aromasin) [package insert]. New York, NY: Pfizer, Inc.; 2019.

 27.  Letrozole (Femara) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; 2018.

 28.  Fulvestrant (Faslodex) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2019.

(Revised 2/2020; NCCN Uterine Neoplasms Guidelines. V5.2019) © 2020 by Haymarket Media, Inc.