Ovarian Cancer

About Ovarian Cancer

1 in 80 women will develop ovarian cancer during their lifetime. This is the fifth-ranked cancer-related death among women.

The ovaries are part of the female reproductive system, where the egg cells are produced for the reproductive process. The ovaries are also the main source of female hormones: Estrogen and Progesterone.

The existing therapies used for stage 4 metastatic ovarian cancer are not curative, and this is a source of the need for innovative and effective treatment strategies in order to fight the disease.

The National Cancer Institute, NCI, highlights the fact that for a certain group of ovarian cancer patients, the best treatment option is to join one of the many clinical trials existing worldwide aiming to increase their chances of therapeutic success.

This is also recommended by the USA national comprehensive cancer network, NCCN,  (USA national comprehensive cancer network)

“Patients with ovarian, fallopian tube, or peritoneal cancer should be encouraged to participate in clinical trials during all aspects of their diagnosis and treatment”

Types of Ovarian Cancer

Ovarian cancer is diagnosed after taking a biopsy or removing cells from the infected tissue during surgery and the diagnosis is done in the laboratory.

There are different types of ovarian cancer and these are classified according to the ovarian cells from which they develop:

1. Epithelial Ovarian Cancer

Its origin is the epithelial cells coating the ovary. It is the most common ovarian cancer, about 90% of cases. Fallopian Tube Cancer and Primary Peritoneal Cancer are also types of epithelial ovarian cancer.

Five major types of epithelial ovarian cancer

• High-Grade Serous Carcinoma which comprises about 70% of all ovarian carcinomas
• Clear-Cell Carcinoma which comprises about 10% of all ovarian carcinomas
• Endometrioid carcinoma which comprises about 10% of all ovarian carcinomas
• Low-Grade serous carcinoma which comprises less than 5% of all ovarian carcinomas
• Mucinous carcinoma which comprises less than 5% of all ovarian carcinomas

2. Germ Cell Ovarian Cancer

Starts from the reproductive cells of the ovaries and is rare.
Four major types of germ-cell ovarian cancer:

• Dysgermnimoma
• Endodermal sinus tumor, EST
• Teratoma
• Mixed germ cell tumor, GCT

Other types in this group are very rare, such as:

• Embryonal carcinoma
• Polyembryoma

• Choriocarcinoma

3. Stromal Cell Ovarian Cancer

Arises from connective tissue cells and is very rare.
The most common types in this group are:

• Granulosa-theca tumors, GCTs
• Sertoli-Leydig cell tumors

4. Small Cell Carcinoma of the Ovary, SCCO

Is an extremely rare ovarian cancer and it is not certain whether the cells in SCCO are formed from.
Two types in this group:

• Hypercalcemic
• Pulmonary

Not every ovarian tumor is necessarily cancerous.

Stage 4 Metastatic Ovarian Cancer

Stage 4 metastatic ovarian cancer is a cancer that started in the ovarian and its cells have spread to other body organs, distant from the ovarian, and created new lesions. These lesions are called “metastases” and are made of ovarian cancer cells.

Ovarian cancer metastases may appear in the bones, liver, lungs and brain. The formation of metastases constitutes a threat on life.

Even though the cancer has spread to other organs, it is still defined as a ovarian cancer and is treated as ovarian cancer. In this manner for example, a lesion in the lung that is a metastasis of ovarian cancer shall be treated with ovarian cancer drugs and not lung cancer drugs.

Risk Factors for Ovarian Cancer

• Age
• Obesity
• First menstrual period at a young age and before the age of 12
• Dense ovarian tissue in mammography
• Family history and first tier relations with a ovarian cancer patient, or a disease in the past
• Presence of the mutations BRCA1 and BRCA2
• Presence of the genes PTEN, , CHEK2 MLH1, MLH3, MSH2, MSH6, TGFBR2, PMS1, and PMS2 , STK11 (Peutz Jegher syndrome), MUTYH (Patients with polyps in the colon)

Symptoms

• A lump in the ovarian that is palpable
• A swelling of the ovarian or the armpit area, a change in the ovarian appearance or a drop of the ovarian
• Reddish, inflamed and rough looking (“orange peel” texture) or irritated ovarian skin
• The nipple is enlarged, bleeding, swollen, inflamed or retreating in

Treatment Goals

The goal of treating local ovarian cancer, not metastatic, is to remove and eradicate the tumor completely.

In metastatic stage 4 disease, the primary objective of the treatment is to slow down and control disease progression and help reduce symptoms as well prolong life and improve patient’s quality of life.

Standard Treatments

A number of therapies are possible, and many patients shall receive more than one type of therapy

Surgery

The surgery’s goal is to remove the tumor in its entirety without harming the ovarian or its function.

At present, multiple innovative surgeries are offered to patients, which allow reduction of the health and cosmetic damages caused to the ovarian. It is considered a success when a tumor is removed in full, however, not all surgeries are necessarily so. At times the tumor is branched and can only be partially removed.

In patients with genetic disposition there are cases where both ovaries are removed in order to prevent a recurrence of the disease, for example patients who are BRCA gene carriers.

Two main types of treatment may be offered to patients before and after surgery

• Treatment prior to surgery is known as ‘Neoadjuvant’ 

Usually this stage of treatment will involve chemotherapy and/or radiotherapy intended to reduce the tumor’s size and improve the success of surgery.

• Post-surgery treatment, also known as ‘Adjuvant’ 

This treatment seeks to cure and prevent the appearance of metastases or recurrence of the tumor.
Ovarian cancer, when metastasized is categorized as stage 4, is considered inoperable.

Radiotherapy

This involves use of radiation at higher levels of energy aims to kill the cancer cells remaining in the post-operative area.

Radiation may also cause decelerated growth of the localized tumor remaining in the area, or local recurrence.

In many cases, Neoadjuvant radiation will be used to shrink and reduce the tumor.

Chemotherapy

Chemotherapy is a medicated therapy which aims to shrink and erase cancerous cells and allow control over the disease.

Chemotherapy carries serious side effects, while its effectiveness is insufficient.

Chemotherapy’s impact has a range of side effects such as hair loss, loss of appetite, changes to bowel movements, fatigue, infection, hemorrhaging, incontinence, pain, and more.

Common chemotherapy treatments for ovarian cancer include:

• Texanes, e.g. Taxol, Taxotere, Docetaxel
• Abraxane® (Paclitaxel)
• Anthracyclines, e.g. Doxorubicin, Doxil, Epirubicin
• Navelbine® (Vinorelbine)
• Xeloda® (Capecitabine)
• Gemzar® (Gemcitabine)
• Hycamtin®, topotecan

Hormonal Therapy

The role of these drugs is to block the estrogen receptor, anti-hormonal, anti-estrogen drugs.

LHRH agonist

Drugs which prevent the ovaries from producing estrogen hormones and are given as an injection every 1-3 months and possible side effects are hot flushes and vaginal dryness.

For example,

• Zoladex® (Goserelin)
• Lucrin® (Leuprolide)
• Tamoxifen

Drugs that reduce estrogen levels

• Arimidex® (Anastrozole)
• Femara® (Letrozole)

Biological Therapies

Anti – Angiogenesis

Cancer tumors survive and thrive in the body by causing the body to produce a system of blood vessels around them that nourishes them and provides them with oxygen.

Anti – angiogenesis agent is a biological antibody which harms the cancerous tumor capability to induce blood vessels growth around it from the environment where it is located, to nourish it so it continues to grow and proliferate. In this way the tumor is “starved” to death.

Examples of angiogenesis inhibitors

• Avastin® (Bevacizumab)

Targeted Therapies (by mutation or a protein)

A mutation is a change in the cell’s DNA sequence, the genetic code of the cell. Mutations may occur when mistakes happen during the cell’s division process, or they may be caused by exposure to DNA harming agents such as free radicals, asbestos and others.

At times healthy cells mutations may cause the generation of cancer in the body.

PARP  inhibitors for BRCA1,2 gene mutation – 

An example of a common mutation in ovarian cancer and a drug that acts to fight it

•  Lynparza® (Olaparib)
• Rubraca® (Rucaparib)
• Zejula® (Niraparib)

Clinical Trials for Ovarian Cancer

Facts

1. The existing therapies used on stage 4 metastatic ovarian cancer are not curative, and this is a source to the need for innovative and effective treatment strategies in order to fight the disease.

2. The National Cancer Institute, NCI, highlights the fact that for a certain group of ovarian cancer patients, the best treatment option is to join one of the many clinical trials existing worldwide aiming to increase their chances of therapeutic success. This is also recommended by the NCCN – (USA national comprehensive cancer network)

“Patients with ovarian, fallopian tube, or peritoneal cancer should be encouraged to participate in clinical trials during all aspects of their diagnosis and treatment”

3. Currently, every patient will be offered the standard protocols described above. Sometimes the oncologist may suggest integrating these therapies with trials carried out in the institute.

The opportunity

1. Advances in cancer therapies may be found in clinical trials prescribing cutting edge, innovative drugs, some of which have already been recognized by the US Food & Drug Administration, the FDA, as “breakthrough drugs” and require further information to be approved.
2. An entire world of clinical trials, Compassionate drugs and advanced new cancer treatments are available worldwide.
3. It is important to know and have access to cutting edge cancer treatments that best match the unique medical condition of the patient and increase chances in winning the fight against compared to the standard care offered.

Note to remember!

Not every patient is eligible to enter a specific clinical trial. The eligibility conditions must be fully met and each case is reviewed separately to ensure that the clinical trial matches to the specific cancer patient and vice versa.

References:
https://www.fda.gov
https://www.ema.europa.eu
https://www.health.gov.il/Pages/HomePage.aspx
https://www.cancer.gov/
https://www.cancer.org
https://www.cancerresearchuk.org
https://www.cancercenter.com/
http://mbcn.org/
ovariancancer.org

Dear Reader,
This information is provided as a source of knowledge and does not constitute a medical consultation. For professional medical advice, see your attending physician. Information regarding drugs and commercial names belongs to the pharmaceutical companies.