Types of Uterine Cancer Medications

What are uterine cancer medications?

Uterine cancer medications are drugs used to treat cancers of the uterus. Surgery is typically the primary treatment for uterine cancers, followed by radiation. Medications are usually prescribed in more advanced stages of uterine cancer.

Uterine cancer medications include chemotherapy, hormone therapy, targeted therapy, and immunotherapy. 

Chemotherapy is used to treat high-grade cancers that grow and spread fast or recur after treatment. Commonly used chemotherapy medications include paclitaxel, doxorubicin, and docetaxel.

Hormone therapy used in uterine cancer treatment is different from the hormone replacement therapy used to relieve menopause symptoms. Hormones or hormone-blocking agents are used to slow cancer cell growth, often in addition to chemotherapy which kills cancer cells. The most common hormone therapy medications are progestins such as megestrol.

Targeted therapy does not kill cancer cells, but specifically targets certain cellular mechanisms to inhibit cancer cell growth and division. Targeted therapy medications for uterine cancer include medications such as lenvatinib, pazopanib, bevacizumab, and everolimus.

Immunotherapy medications boost the immune system’s ability to identify and kill cancer cells. A commonly used immunotherapy medication in uterine cancer treatment is pembrolizumab.

The FDA-approved medications for endometrial cancers (cancers that begin in the cells that line the uterus) are:

  • Lenvatinib mesylate
  • Megestrol acetate
  • Pembrolizumab

How do uterine cancer medications work?

Chemotherapy

Chemotherapy medications kill cancer cells, but they also kill healthy cells which are in the phase of growth and division. Chemotherapy drugs are more toxic to cancer cells because cancer cells are always growing and dividing. Chemotherapy also shrinks tumors, eases cancer symptoms, and enhances the effects of radiation.

Chemotherapy is often used in more advanced stages in endometrial cancers, but in uterine sarcomas, it seems to have better results in the early stages.

Chemotherapy is usually given as a combination of two or more drugs in three to six-weekly cycles with rest periods in between for recovery from side effects. Antiemetics are commonly prescribed with chemotherapy to prevent side effects such as nausea and vomiting.

Commonly used chemotherapy medications for endometrial carcinomas include:

  • Paclitaxel
  • Cisplatin
  • Carboplatin
  • Doxorubicin hydrochloride (Adriamycin)
  • Liposomal doxorubicin (Doxil)
  • Docetaxel (Taxotere)

Chemotherapy medications used for uterine sarcomas include:

  • Dacarbazine
  • Docetaxel (Taxotere)
  • Doxorubicin hydrochloride (Adriamycin)
  • Liposomal doxorubicin (Doxil)
  • Epirubicin hydrochloride (Ellence)
  • Gemcitabine hydrochloride (Gemzar)
  • Ifosfamide (Ifex)
  • Paclitaxel
  • Temozolomide (Temodar)
  • Trabectedin (Yondelis)
  • Vinorelbine tartrate

Hormone therapy

Most hormone therapies block estrogen production in the body to arrest cancer growth. Hormone therapy is typically used to treat advanced and recurring endometrial cancers, and also endometrial stromal carcinoma, but rarely used for other uterine sarcomas. Hormone therapy is often used along with chemotherapy. The types of hormone therapy include:

  • Progestins: Progestins are synthetic forms of the female hormone, progesterone. The two commonly used progestins to treat uterine cancers are:
  • Megestrol acetate (Megace ES)
  • Medroxyprogesterone acetate (Provera)
  • Tamoxifen citrate: Tamoxifen is an anti-estrogen drug that may be alternated with progestins in advanced endometrial cancers.
  • Gonadotropin-releasing hormone (GNRH) agonists: Also known as luteinizing hormone-releasing hormone (LHRH) agonists, GNRH agonists block the ovaries from making estrogen. GNRH agonists are useful for premenopausal women who have retained their ovaries. GNRH agonists include:
  • Goserelin acetate (Zoladex)
  • Leuprolide acetate (Lupron Depot)
  • Aromatase inhibitors: Aromatase inhibitors block the production of estrogen by fat cells. Aromatase inhibitors include:
  • Letrozole (Femara)
  • Anastrozole (Arimidex)
  • Exemestane (Aromasin)

Targeted therapy

Targeted therapy medications are small molecule medications which are tiny synthetic protein molecules or monoclonal antibodies which are lab-engineered human antibodies. Targeted therapy is still an evolving treatment in uterine cancers, though an established treatment in many other cancers.

Targeted therapy medications include:

  • Kinase inhibitors: Kinase inhibitors are small molecule drugs to treat advanced or recurrent high-grade endometrial carcinomas. Kinase inhibitors block the activity of proteins known as kinases which help cancers grow and also inhibit the growth of new blood vessels (angiogenesis) in tumors. Kinase inhibitors used to treat uterine cancers are:
    • Lenvatinib mesylate (Lenvima) for endometrial carcinoma
    • Pazopanib hydrochloride (Votrient) for uterine leiomyosarcoma
  • Vascular endothelial growth factor (VEGF) inhibitors: VEGF inhibitors are monoclonal antibodies that block the activity of VEGF, a protein that is essential for angiogenesis in tumors. VEGF inhibitor used to treat endometrial carcinomas is:
  • mTOR inhibitors: mTOR inhibitors are drugs that block the activity of proteins known as mechanistic targets of rapamycin (mTOR), which help cells grow and divide. mTOR inhibitors may be given along with chemotherapy or hormone therapy. mTOR inhibitors that are used for advanced and recurrent endometrial cancers include:
    • Everolimus (Afinitor)
    • Temsirolimus (Toricel)

Immunotherapy

Immunotherapy enhances the woman’s own immune system’s ability to kill cancer cells. Immunotherapy is used to treat certain types of endometrial cancers which are linked to errors in DNA copying during cell division. Immunotherapy is not used to treat uterine sarcomas. Immunotherapy may be used along with targeted therapy.

The immunotherapy medication used to treat endometrial cancer is:

  • Pembrolizumab (Keytruda): Pembrolizumab is a monoclonal antibody which blocks a protein known as PD-1 found in T-cells, a type of killer immune cell. PD-1 is a regulatory protein that prevents the T-cells from attacking the body’s cells. Blocking PD-1 boosts T-cell activity against the cancer cells.

Additional information

  • Please visit our medication section of each drug within its class for more detailed information.
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  • Never stop taking your medication and never change your dose or frequency without consulting with your doctor.

SLIDESHOW

Signs of Cancer in Women: Symptoms You Can't Ignore See Slideshow

What is uterine cancer?

Uterine cancers are cancers that originate in the uterus. Cancer is an uncontrolled growth of abnormal cells that defy the normal cell cycle of growth, division, and programmed death at the appropriate time, and instead, continue growing and dividing.

Cancers often form clumps of growth called tumors which grow to the detriment of healthy cells in the region. Uterine cancers that spread to other parts of the body are termed malignant (metastatic).

The uterus is a pear-shaped reproductive organ located in a woman’s pelvis. The uterus has three parts:

  1. Fundus: The dome-like top part
  2. Isthmus: The broad middle section
  3. Cervix: The lower section that connects the uterus to the vaginal canal

The uterus is a hollow muscular organ with three layers:

  1. Endometrium: The inner lining that grows blood vessels every month, which is shed during menstruation if no pregnancy occurs
  2. Myometrium: Myometrium is the muscular layer over the endometrium
  3. Serosa: The thin outer lining that encloses the uterus

Types of uterine cancer

Uterine cancer is the most common gynecological cancer. Only cancers that develop in the body of the uterus are called uterine cancers. Cancer of the cervix is called cervical cancer and is treated differently from other cancers of the uterus.

Benign tumors

Common benign growths in the uterus which do not spread include:

  • Fibroids: Growths in the myometrium
  • Benign polyps: Growths in the endometrium
  • Endometriosis: Growth of endometrial tissue outside the uterus
  • Endometrial hyperplasia: Increased thickness of endometrial lining, which has a potential risk for cancer if atypical cells are present
  • Leiomyoma: Tumor in the uterus muscle layer
  • Adenofibroma: Rare type of tumor in the glandular and fibrous tissue
  • Adenomyoma: Tumor in the glandular and muscle tissue

Malignant cancers

Uterine cancers are classified into three grades, depending on how much the cancer cells look abnormal. Grade 1 and 2 cancers have fewer abnormal-looking cells and are less aggressive. Grade 3 cancers are considered high-grade cancers in which most cells look abnormal and are more likely to grow fast and spread.

Uterine cancers are mainly of two kinds, endometrial carcinomas which start in the endometrium, and uterine sarcomas which start in the myometrium.

Endometrial carcinoma

Endometrial carcinoma is the most common uterine cancer accounting for approximately 90% of uterine cancers. Up to 75% of endometrial cancers occur in postmenopausal women.

The most common type of endometrial cancer is:

  • Adenocarcinoma: Adenocarcinoma is cancer that starts in the glandular cells of the endometrium. Most endometrial cancers are adenocarcinomas, and the other types form only a small percentage of endometrial cancers. The types of endometrial adenocarcinoma include:
    • Endometrioid cancer: Endometrioid cancer is the most common adenocarcinoma and has many subtypes.

Less common endometrial adenocarcinomas include:

  • Clear-cell carcinoma
  • Mucinous adenocarcinoma
  • Undifferentiated carcinoma
  • Dedifferentiated carcinoma
  • Serous adenocarcinoma

Rare types of endometrial cancers include the following:

  • Uterine carcinosarcoma: Also known as malignant mixed mesodermal tumors (MMMTs), uterine carcinosarcoma has features of both carcinoma and sarcoma. Carcinomas start in the cells that make up skin and organ lining, and sarcoma starts in muscle tissue.
  • Squamous cell carcinoma: Starts in the squamous cells, a flat type of cells in the endometrium.
  • Small cell carcinoma: Starts in neuroendocrine cells, which are a type of nerve cells that also produce hormones.
  • Transitional carcinoma: An extremely rare variant of endometrial cancer in transitional cells which are typically found in the urinary tract.
  • Papillary serous carcinoma: A rare type of cancer that develops in the endometrium due to atrophy of the uterus.

Endometrial cancers are of two primary types:

  • Type I: More than 80% of endometrial cancers are type I, which are believed to be caused by too much estrogen. Endometrioid grade 1 and 2 cancers are Type I endometrial cancers.
  • Type II: Type II cancers are high-grade cancers that are thought to be estrogen-independent, and occur in older women. The rarer types of endometrial carcinomas and grade 3 endometrioid cancers are type II.

Uterine sarcoma

Uterine sarcomas account for less than 9% of uterine cancers. Uterine sarcomas start in the muscle wall of the uterus and can spread rapidly. Types of uterine sarcomas include the following:

  • Uterine leiomyosarcoma (LMS): The most common type of uterine sarcoma.
  • Undifferentiated sarcoma: These cancers may start in the endometrium or myometrium and can grow fast.
  • Endometrial stromal sarcoma (ESS): Rare and less aggressive cancer that starts in the connective tissue (stroma) that supports the endometrium. Low-grade ESS tend to grow slowly.

Stages of uterine cancer

Uterine cancers are staged as follows:

  • Stage I: Cancer is contained within the uterus.
  • Stage II: Cancer has spread from the body of the uterus into the connective tissue that supports the cervix (cervical stroma).
  • Stage III: Cancer has spread into the tissue outside the uterus and/or into the fallopian tubes, ovaries, vagina, or nearby lymph nodes.
  • Stage IVA: Cancer has spread into the inner lining of the bladder and rectum and/or nearby lymph nodes.
  • Stage IVB: Cancer has spread to nearby lymph nodes and/or distant organs such as the upper abdomen, lungs, liver, or bones.

What are the symptoms of uterine cancer?

The symptoms of uterine cancer include the following:

  • Abnormal vaginal bleeding or spots such as:
    • Bleeding between periods
    • Uncommonly heavy or prolonged menstrual bleeding
    • Bleeding after menopause
  • Abnormal discharge without blood
  • Pelvic pain
  • Palpable pelvic mass
  • Unexplained weight loss
  • Change in bladder and bowel habits

What are the risk factors of uterine cancer?

The exact cause of uterine cancer is not clear and scientists are studying what gene mutations may cause uterine cancer. There are several risk factors that appear to have a strong link to both endometrial carcinomas and uterine sarcomas:

  • Advanced age: The average age at which uterine cancer is diagnosed is 60. Uterine cancer is uncommon in women younger than 45.
  • Race: White women appear to have a higher risk for developing uterine cancer, but black women have a higher risk for late diagnosis and consequently, a higher risk for advanced cancer and higher mortality.
  • Estrogen: Excess estrogen levels in the body because of:
  • Diet: Diet high in animal fat.
  • Radiation: Radiation therapy for other cancers in the pelvic region.
  • History of cancer: Personal history of other cancers such as breast, colon, or ovarian cancer, or a family history of hereditary cancers such as Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC).
  • Endometrial hyperplasia: Presence of atypical cells with endometrial hyperplasia.
  • Diabetes: Diabetes is a risk factor because it is often associated with obesity.

There are no known ways to prevent uterine cancers. Maintaining a healthy weight, eating healthy, and staying active can help reduce the risks of developing cancer. It might be a good idea to consider the pros and cons before opting for hormone therapy and seek prompt treatment for any abnormal vaginal discharge or bleeding.

What is the survival rate for cancer of the uterus?

The overall five-year survival rate for endometrial cancer is 81% in white women and 62% in black women. The prognosis is good for endometrial cancers if they are detected early, but uterine sarcomas on the whole have poorer outcomes.

The five-year survival rates for different stages of endometrial cancer are as follows:

  • Localized: 95%
  • Regional spread: 69%
  • Distant spread: 17%

The overall five-year survival rate for leiomyosarcoma and undifferentiated sarcoma is 41% and 43% respectively, but greatly better at 95% for endometrial stromal sarcoma.

What is the common treatment for cancer of the uterus?

Treatment for uterine cancer depends on the grade and stage of cancer. surgery is the primary treatment for almost all uterine cancers. Surgery is most often followed by radiation and/or chemotherapy to prevent cancer from recurring. Advanced cancers will require additional therapies. It is also possible to enroll in clinical trials for new treatments.

Standard treatment for uterine cancers include the following:

  • Surgery: Surgery may involve one or more of the following procedures:
    • Total hysterectomy: Removal of the uterus, to treat early-stage low-grade tumors.
    • Radical hysterectomy: Removal of the uterus, ovaries, fallopian tubes, top part of the vaginal canal, and connective tissue supporting the uterus, to treat high-grade or stage II cancers.
    • Lymphadenectomy: Removal of all the nearby lymph nodes in the pelvis, or sentinel lymph nodes which are lymph nodes where the cancer is likely to spread first.
    • Pelvic washing: The pelvic area is often washed with saline after the surgery, and the fluid is suctioned out and tested for the presence of cancer cells.
    • Omentectomy: Removal of the fatty tissue known as omentum which lies over the abdomen, for biopsy purposes or if cancer has spread to the omentum.
    • Tumor debulking: If the tumor has spread in the abdominal region, the surgeon may remove as much of the tumor as possible before treatment with chemotherapy and/or radiation.
  • Radiation therapy: Radiation therapy uses high-energy X-rays to destroy cancer cells. Radiation is most often performed after surgery, but may sometimes be done to shrink the tumor before surgery. Radiation therapy may be of two types:
    • External beam radiation therapy: X-rays are directed at the uterus from a device that is placed outside the body.
    • Brachytherapy: Brachytherapy is internal radiation, in which the X-ray device is placed inside the vagina.
  • Medications: Different types of medications are prescribed in most stages of uterine cancer. The type of medications varies with the stage of cancer. Medications may be administered orally, by injections, or intravenous infusions. Some of the medications are approved by FDA specifically for uterine cancers, but many are prescribed because of proven clinical efficacy.

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References
https://emedicine.medscape.com/article/258148-treatment#d18

https://www.cancer.org/cancer/endometrial-cancer/causes-risks-prevention/prevention.html

https://www.cancer.org/cancer/uterine-sarcoma/treating/by-stage.html

https://www.cancer.net/cancer-types/uterine-cancer/introduction

https://www.cancercenter.com/cancer-types/uterine-cancer/about

https://www.cdc.gov/cancer/uterine/basic_info/index.htm

https://www.cancer.gov/about-cancer/treatment/drugs/endometrial