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How Novartis’ Afinitor And Herceptin (Trastuzumab) Can Help With Cancer Treatment?

How Novartis’ Afinitor And Herceptin (Trastuzumab) Can Help With Cancer Treatment?

Cancer is a collection of diseases in which the body’s normal cells start to grow abnormally and uncontrollably. Such abnormal cells can also penetrate normal body tissues and destroy them. When the control mechanism of the body does not work normally, it results in the development of cancer. Cancer can develop anywhere in the body (1).

How Does Cancer Develop?

When there is a requirement in the body, the cells divide and grow to develop new cells. These new cells take the place of old or damaged cells. But in cancer, these old and damaged cells are not replaced by new cells. Instead, these old and damaged cells start to grow uncontrollably and form new abnormal cells (2).

What Are the Types of Tumors?

A mass of tissues is formed by these new abnormal cells known as a tumor. Whereas in blood cancer, such as leukemia, a tumor is not formed. Tumors can be malignant. This means that such types of cancer cells can invade the surrounding tissues and spread to the body’s nearby tissues. Additionally, they can cause metastasis. It means these abnormal cells can break off from the original tumor and travel through the blood or lymphatic system to other organs located far from the original place of the tumor (3).

Another type of tumor is called benign tumors. In contrast to malignant tumors, benign tumors do not penetrate the surrounding tissues. However, their size may become quite large sometimes. After surgical removal, malignant tumors have chances to grow sometimes, but benign tumors do not grow back. Although most benign tumors in the body do not pose any threat, life-threatening situations can result from benign tumors in the brain (3).

Treatment of Cancer

Many types of treatments are available for cancer. The type of cancer and how much it has advanced decide which kind of treatment will be used. In some cases, only one type of therapy is used. But in most cases, a combination of treatments is utilized. Surgery is combined usually with chemotherapy or/and radiation therapy. Hormone therapy, targeted therapy, or immunotherapy can also be used (4).

Here we will discuss two medicinal products, Afinitor and Herceptin, and their role in cancer treatment. 

What Is Afinitor?

Everolimus is the medicine substance present in Afinitor. It is an antineoplastic agent (which inhibits tumor growth) and is used to treat certain types of tumors, cancers, and seizures. Everolimus is a kinase inhibitor that blocks enzyme kinase. This enzyme is helpful in many functions, such as metabolism, survival, division, and signaling in cells (5).

In some cancer cell types, the action of specific kinases is very prominent, and when these kinases are blocked, it helps in the prevention of cancer cell growth. Additionally, the development of new blood vessels around the cancer cells is also inhibited by the kinase inhibitors (6).

Which Type of Cancers Are Treated by Afinitor?

Afinitor has been approved by the Food and Drug Administration (FDA) to treat the following cancers and tumors:

1. Breast cancer: Women with menopause having Advanced hormone receptor-positive, HER2-negative breast cancer in which letrozole or anastrozole therapies have failed. Afinitor is recommended to be used with anticancer drug exemestane.

2. Renal Cell Carcinoma: Adults who have advanced renal cell carcinoma (Cancer of kidneys) in which anticancer drugs sunitinib or sorafenib have failed previously to produce results.

3. Neuroendocrine Tumors: Adults who have tumors of the lungs, pancreas, or stomach cannot be removed surgically.

4. Renal angiomyolipoma: It is a type of benign tumor in the kidney in adults that is not cancerous Such patients also have the genetic disorder tuberous sclerosis (5). 

How Does Afinitor Act?

Afinitor inhibits mammalian target of rapamycin (mTOR) which is a serine-threonine kinase. mTORs work as targeted therapies in which there is direct targeting and then attacking cancer cells.

Unlike chemotherapy, Afinitor affects the specific cancer cells, which produces its effects on all cells of the body.

Additionally, Afinitor also inhibit the growth of new blood vessels to the tumor by reducing the levels of specific growth factors, such as vascular endothelial growth factor (VEGF) (5).

Benefits Of Afinitor

A clinical study was carried out in postmenopausal women with HER2-Negative Breast Cancer. 12.6% was the response rate in women who took a combination of Afinitor and exemestane. However, 1.7% was the response rate in women who took only exemestane. The response rate is defined as the percentage of decrease in Cancer cells or the disappearance of Cancer cells after treatment (5).

Similarly, in another clinical study, patients with kidney cancer treated with Afinitor showed a response rate of 2% compared to patients who only received supportive care and no medication for cancer treatment (response rate 0%). Additionally, the time people lived was also more than doubled with the use of Afinitor without the condition of their cancer becoming worse (7).

Side Effects of Afinitor

Common side effects of Afinitor include nausea, diarrhea, vomiting, constipation, weight loss, decreased appetite...

Common side effects of Afinitor include nausea, diarrhea, vomiting, constipation, weight loss, decreased appetite, changes in taste or unusual taste in the mouth, pain or sores in the mouth and throat, acne, dry skin, skin rash, nosebleeds, headaches, temporary hair loss, cold symptoms (stuffy nose, sneezing, sore throat), or pain in your arms and legs (5).

What Is Herceptin?

Trastuzumab is the medicine substance present in Herceptin used to treat HER2-positive breast cancer. Trastuzumab is a monoclonal antibody, and it is a part of a chemotherapy regimen (8). Monoclonal antibodies are man-made proteins that act similarly to antibodies already present in the immune system of the human body (9).

Which Cancers Are Treated by Herceptin?

FDA has approved Herceptin to treat the following:

  1. Metastasis of HER2-positive breast cancer: Herceptin helps prevent the further growth of cancer cells from the breast to other body parts like the uterus.
  2. Earlier stages of HER2-positive breast cancer: Herceptin is used in the treatment of HER2-positive breast cancer either alone or in combination with the chemotherapy regimen that may include anthracycline. Anthracycline is used to stop cancer from coming back.
  3. It is also used in combination with pertuzumab and docetaxel to treat inflammation of early stage, before surgery for treating HER2-positive breast cancer, or breast cancer, which is locally advanced and has high chances of metastasizing to other parts.
  4. HER2-positive gastric (stomach) cancer: Herceptin is also used in the treatment of gastroesophageal junction adenocarcinoma (stomach cancer) and also helps in the prevention of its metastasis (10).

How Does Herceptin Act?

There are many receptors present on the surface of the cancer cell. Changes in the cancer cells occur when chemicals bind with these receptors. A lot of HER2 receptors are present in both HER2-positive breast and stomach cancer cells. These HER2 receptors help send signals to the cancer cells, telling them to grow and rapidly divide, which causes the development of tumors.

HER2 receptors are specifically “targeted” by the Herceptin to stop the cell growth of tumors. Herceptin becomes attached to the HER2 receptors and tells the tumor cells to stop dividing and growing. Additionally, the body’s immune system is also signaled by Herceptin to start destroying cancer cells (10).

Benefits of Herceptin

The FDA has recommended the use of Herceptin with pertuzumab and docetaxel to inhibit metastasis of breast cancer. In a clinical study, 39% of the patients who took the combination therapy of Herceptin, pertuzumab, and docetaxel for 12 weeks and had surgery for breast cancer removal did not show any presence of cancer cells or growth in their breast (11). 

Side Effects of Herceptin

The common side effects observed when using Herceptin to treat breast cancer are nausea, diarrhea, headache, insomnia, skin, upper respiratory tract, or urinary tract infection, rash, cough, hot flashes, swelling, chills, fever, depression, or joints, back or belly pain

HER2 receptors are also present in normal human cells. Herceptin may get attached to these normal cells, which may result in possible side effects. The common side effects observed when using Herceptin to treat breast cancer are nausea, diarrhea, headache, insomnia, skin, upper respiratory tract, or urinary tract infection, rash, cough, hot flashes, swelling, chills, fever, depression, or joints, back or belly pain (10).

The common side effects observed when using Herceptin to treat stomach cancer are lack of energy, runny nose, cough, sore throat, no or decreased taste, weight loss, swelling of mouth, lips, throat, and inside cheeks, or fever (10).

Herceptin may cause heart-related side effects as well. Therefore, it is recommended to take precautions while taking Herceptin. In a clinical study, patients who were taking standard chemotherapy treatment with Herceptin experienced more heart-related side effects in comparison to patients who only took standard treatment. If a patient experiences weakness, dizziness, racing heart, chest pain, swelling, fainting, rapid weight gain, or palpitations, a doctor must be consulted immediately. Similarly, a clinical study reported that 6 to 20% of the patients receiving Herceptin experienced depression (11).

Conclusion

Both Afinitor and Herceptin have been widely used by doctors in the treatment of cancers for many years. Positive outcomes have been observed in cancer patients with the use of these two drugs. However, it is recommended that in case of persistent side effects or any unusual outcome, the patient should immediately consult their doctor. 

References:

  1. Weinberg RA. How Cancer Arises. Scientific American. 1996;275(3):62–70.
  2. Mayo Clinic. Cancer – Symptoms and causes [Internet]. Mayo Clinic. [cited 2021 Mar 4]. Available from: https://www.mayoclinic.org/diseases-conditions/cancer/symptoms-causes/syc-20370588
  3. National Cancer Institute. What Is Cancer? [Internet]. 2015 [cited 2021 Mar 4]. Available from: https://www.cancer.gov/about-cancer/understanding/what-is-cancer
  4. National Cancer Institute. Treatment for Cancer [Internet]. 2015 [cited 2021 Mar 4]. Available from: https://www.cancer.gov/about-cancer/treatment
  5. Novartis Pharmaceuticals. AFINITOR® (everolimus) – Prescribing Information [Internet]. 2020 [cited 2021 Mar 4]. Available from: https://www.us.afinitor.com/
  6. National Cancer Institute. Definition of kinase inhibitor [Internet]. 2011 [cited 2021 Mar 4]. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/kinase-inhibitor
  7. Nguyen V. Afinitor: Side effects, cost, uses, and more (everolimus) [Internet]. MedicalNewsToday. 2019 [cited 2021 Mar 4]. Available from: https://www.medicalnewstoday.com/articles/326055
  8. Ogbru O. Herceptin (trastuzumab) for Breast Cancer (HER2) Side Effects & Dosage [Internet]. MedicineNet. [cited 2021 Mar 4]. Available from: https://www.medicinenet.com/trastuzumab/article.htm
  9. American Cancer Society. Monoclonal Antibodies and Their Side Effects [Internet]. 2019 [cited 2021 Mar 4]. Available from: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/monoclonal-antibodies.html
  10. Genentech, Inc. What is Herceptin® (trastuzumab) for HER2+ Cancer? [Internet]. [cited 2021 Mar 4]. Available from: https://www.herceptin.com/patient/about-herceptin.html
  11. Miller K. Herceptin: Side effects, dosage, uses, and more [Internet]. 2020 [cited 2021 Mar 4]. Available from: https://www.medicalnewstoday.com/articles/herceptin
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