Leiomyosarcoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:  Nima Nasiri, M.D.[2]

## Overview

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Uterine leiomyosarcoma (LMS) is the most common sarcoma arising from the uterus and comprises approximately 2% of uterine cancers. Patients diagnosed with LMS have a 5-year overall survival ranging from 25-75% . The primary management of LMS is hysterectomy. Adjuvant pelvic radiotherapy has been shown to improve local control and survival of patients with leiomyosarcoma.

## Chemotherapy

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* Chemotherapy is recommended for individuals who have locally advanced, metastatic, or recurrent disease. Usually in combination with surgical procedures and/or radiation. The treatment is to use drugs to stop the growth of cancer cells either by killing the cells or by stopping them from dividing.[1][2][3]
* Anthracyclines stops the tumor growth by different mechanism such as intercalating into deoxyribonucleic acid (DNA), blocking DNA and ribonucleic acid (RNA) synthesis, also causing DNA breakage by interfering with topoisomerase II activity.
* Most common drugs used as first line treatment of soft tissue sarcoma include combination of ifosfamide and doxorubicin (Adriamycin).
* Surgical resection of localized disease is a mainstay therapeutic strategy.
* In the event tumors have metastasized or spread beyond uterus and not resectable by surgery, cytotoxic chemotherapeutic agents can be used in combination with radiation therapy.
* Some of these chemotherapeutic agents are gemcitabine, docetaxel, ifosfamide, temozolomide, trabectedin, eribulin.

* Regimen includes the following:[4][5][6][7]
* Doxorubicin 60 mg/m2 every 3 wk; doses as high as 75 mg/m2 can be given; however, this can be administered as a split dose over 3 d (25 mg/m2/day for 3 d); maximum lifetime dose is 475-600 mg/m2 or

* Liposomal pegylated doxorubicin: doses as high as 50 mg/m2 every 4 wk have been used in clinical trials; however, this is associated with significant toxicity; commonly used doses include 30-35 mg/m2 every 4 wk; no maximum lifetime doses or

* Ifosfamide 2000-3000 mg/m2/day IV over 3 h for 3-4 d plus mesna; repeat every 21 d or

* Ifosfamide 5000 mg/m2 over 24 h plus mesna 5000 mg/m2 over 24 h and an additional 400-600 mg/m2 for 2 h after completion of ifosfamide; repeat every 21 d (European schedule) or

* Gemcitabine 1200 mg/m2 IV over 90-120min on days 1 and 8; repeat cycle every 21d or

* Trabectedin 1.5 mg/m2 IV q3wk until disease progression or unacceptable toxicity; premedication require and infuse via central line over 24h
* Epirubicin 160 mg/m2 IV bolus every 3 wk with growth factor support or

* Dacarbazine 250 mg/m2 IV for 5 d or 800-1000 mg/m2 IV every 3 wk or

* Pazopanib 800 mg PO qd (not indicated for liposarcoma outside of a clinical trial; FDA approved as second-line chemotherapy; recommend starting at a low dose of 200 mg for 2 weeks and slowly increasing the dose)

## Radiation Therapy

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* Radiation therapy may be a useful adjunct to improve local control or where a cancer is inoperable due to the specific location or possible progression of the malignancy.[8]
* It can be used postoperative to help treat known or possible residual disease. Radiation therapy can also be used as a palliative care in cases where extensive metastasis has already occurred.[9]

* Adjuvant pelvic radiotherapy has been shown by some to improve disease-free survival. [10]

* Studies had shown that there is a 38% disease-free survival rate in women receiving adjuvant radiotherapy compared with 18% in women receiving surgery alone.[11]

## Novel therapies

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Studies have shown that some of the sarcomas express angiogenic factors, such as vascular endothelial growth factor, therefore the use of anti‐angiogenic agents is reasonable as part of the treatment on case basis.[12]

* Thalidomide, an angiogenesis inhibitor, is currently being investigated to be used for the treatment of leiomyosarcoma.

## References

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1. ↑ In, Gino K.; Hu, James S.; Tseng, William W. (2017). "Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations". Therapeutic Advances in Medical Oncology. 9 (8): 533–550. doi:10.1177/1758834017712963. ISSN 1758-8340.
2. ↑ Blay JY (2018) Getting up-to-date in the management of soft tissue sarcoma. Future Oncol 14 (10s):3-13. DOI:10.2217/fon-2018-0074 PMID: 29768050
3. ↑ (1969) New antiviral drug. Nature 222 (5190):218. PMID: 5778386
4. ↑ Laverdiere C, Kolb EA, Supko JG, Gorlick R, Meyers PA, Maki RG, Wexler L, Demetri GD, Healey JH, Huvos AG, Goorin AM, Bagatell R, Ruiz-Casado A, Guzman C, Jimeno J, Harmon D (August 2003). "Phase II study of ecteinascidin 743 in heavily pretreated patients with recurrent osteosarcoma". Cancer. 98 (4): 832–40. doi:10.1002/cncr.11563. PMID 12910529.
5. ↑ Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD (April 2004). "Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy". J. Clin. Oncol. 22 (8): 1480–90. doi:10.1200/JCO.2004.02.098. PMID 15084621.
6. ↑ Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, Puchalski TA, Goss G, Seiden MV, Waxman A, Quigley MT, Lopez T, Sancho MA, Jimeno J, Guzman C, Demetri GD (August 2005). "Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study". J. Clin. Oncol. 23 (24): 5484–92. doi:10.1200/JCO.2005.05.028. PMID 16110008.
7. ↑ Lopez M, Vici P, Di Lauro L, Carpano S (March 2002). "Increasing single epirubicin doses in advanced soft tissue sarcomas". J. Clin. Oncol. 20 (5): 1329–34. doi:10.1200/JCO.2002.20.5.1329. PMID 11870176.
8. ↑ Sampath, Sagus; Gaffney, David K. (2011). "Role of radiotherapy treatment of uterine sarcoma". Best Practice & Research Clinical Obstetrics & Gynaecology. 25 (6): 761–772. doi:10.1016/j.bpobgyn.2011.06.004. ISSN 1521-6934.
9. ↑ Reed NS, Mangioni C, Malmström H, Scarfone G, Poveda A, Pecorelli S et al. (2008) Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer 44 (6):808-18. DOI:10.1016/j.ejca.2008.01.019 PMID: 18378136
10. ↑ Harry, Vanessa N; Narayansingh, Gordon V; Parkin, David E (2007). "Uterine leiomyosarcomas: a review of the diagnostic and therapeutic pitfalls". The Obstetrician & Gynaecologist. 9 (2): 88–94. doi:10.1576/toag.9.2.088.27309. ISSN 1467-2561.
11. ↑ Harry, Vanessa N; Narayansingh, Gordon V; Parkin, David E (2007). "Uterine leiomyosarcomas: a review of the diagnostic and therapeutic pitfalls". The Obstetrician & Gynaecologist. 9 (2): 88–94. doi:10.1576/toag.9.2.088.27309. ISSN 1467-2561.
12. ↑ Boyar, Michelle S.; Hesdorffer, Mary; Keohan, Mary Louise; Jin, Zhezhen; Taub, Robert N. (2008). "Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma". Sarcoma. 2008: 1–7. doi:10.1155/2008/412503. ISSN 1357-714X.

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