Leiomyosarcoma medical therapy

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

Overview[edit | edit source]

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[edit | edit source]

• 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[edit | edit source]

• 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[edit | edit source]

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[edit | edit source]

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