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Metastatic Breast Cancer: Limited Clinical Benefit of Irinotecan and Etoposide in Patient Treatment

Dec 27, 2019

Estimated reading time: 5 minutes
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Metastatic breast cancer, also known as stage IV breast cancer, is an advanced form of the disease in which cancer has spread to other parts of the body, such as the bones, lungs, liver, or brain. Only a small percentage (6%) of women are initially diagnosed with metastatic breast cancer, with most cases occurring as a result of relapse after prior treatment and a period of remission.

There is a great difference between breast cancers and metastatic breast cancers; breast cancer is an umbrella term for all types and stages of carcinoma that originate in the breast tissue. On the other hand, The National Cancer Institute (NCI) also provides information about metastatic breast cancers and different breast cancer stages, including the definition of metastatic breast cancer as stage IV of the disease, where cancer cells have spread to other parts of the body.

Irinotecan & Etoposide for Breast Cancer

While metastatic breast cancer is most commonly found in women, it also affects a small number of men. According to the American Cancer Society’s Cancer Facts and Figures report from 2019, the 5-year survival rate for metastatic breast cancers is less than 30%.
Segar, Jennifer M et al. “A Phase II Study of Irinotecan and Etoposide as Treatment for Refractory Metastatic Breast Cancer.” The oncologist vol. 24,12 (2019): 1512-e1267. doi:10.1634/theoncologist.2019-0516

Clinical Trial (NCT00693719): Irinotecan and Etoposide in Metastatic Breast Cancer

  • There were 31 women enrolled in this single arm, phase II clinical trial, between ages of 36-84 years.
  • 64% of these women had the hormone positive and HER2 negative type of breast cancer.
  • The women had been treated with a median of at least 5 prior therapies and were already resistant to prior anthracycline, taxane and capecitabine therapy.

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Scientific Rationale for the Study

  • The reasoning behind the trial was to try a new set of chemotherapy drugs that had both shown documented activity in breast cancer patients and the combination was validated preclinically.
  • Both Irinotecan and Etoposide are natural, plant-derived compounds that are modulators of topoisomerase (TOP) enzyme isoforms. TOP enzymes are required for DNA replication and transcription, both critical processes for a rapidly growing cancer cell. Interfering with TOP action causes DNA strand breaks, DNA damage and induces cell death.
  • Irinotecan is a TOP1 and Etoposide a TOP2 modulator. Reason for combining both TOP1 and TOP2 inhibitors is to address the compensatory activation of the other isoform when one of the isoforms is suppressed.

Clinical Trial Results

  • There were 24 patients that could be evaluated for efficacy of this combination regimen of Irinotecan and Etoposide. 17% had a partial response and 38% had stable disease.
  • All 31 patients were evaluated for toxicity and 22 of the 31 (71%) experienced treatment related grade 3 and 4 adverse events. Most common toxicity was neutropenia, which is the presence of abnormally low levels of neutrophils in blood that could increase susceptibility to infections.
  • Study was terminated early since toxicity burden was severe and outweighed the efficacy of the combination.

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Metastatic Breast Cancer Symptoms

  • Bone pain or tenderness: It can spread to the bones, causing pain or tenderness in the affected areas.
  • Fatigue: Cancer and cancer treatments can cause fatigue, which can be severe and persistent.
  • Shortness of breath: Cancer spreading to the lung can cause shortness of breath.
  • Neurological symptoms: Cancer that has spread to the brain can cause neurological symptoms such as headaches, seizures, or changes in mental function.
  • Loss of appetite and weight loss: Cancer and cancer treatments can cause loss of appetite and weight loss.
  • Jaundice or swelling in the belly when cancer has spread to the liver.

The life expectancy of someone with metastatic breast cancer can vary depending on several factors such as the location and spread of the tumor.

According to a study, the 5-year survival rate for is a measure of how many people with this type of cancer are still alive in the last 5 years after the cancer is found. It is expressed as a percentage, meaning the number of people out of 100 alive after 5 years. According to the American Cancer Society, the 5-year survival rate for women with metastatic breast cancer is 29%, while the 5-year survival rate for men with is 22%. It’s important to note that these are general statistics and individual cases may vary.

Treatment of Metastatic Breast Cancer

The treatment is complex but a combination of chemotherapy with specific chemo drugs has some benefits in controlling cancer. It cannot be used extensively and long term due to its severe toxicity profile and quality of life impact on the patient. Immunotherapy treatment is another option that can be considered for patients with metastatic breast cancers; this treatment approach can help the body’s immune system recognize and attack cancer cells.

Evaluating the mutation profile of the metastatic tumor could also help identify combinations of more targeted therapy approaches with lower side effects. The risk of using the specific combination of topoisomerase inhibitors Irinotecan and Etoposide outweighed the benefits and may not be used in treating metastatic breast cancers.  

Since every metastatic breast cancer is unique with its own set of genomic variations, the treatment options are personalized accordingly by the oncologists.  There is still work to be done in finding improved and safe treatment options for it.  Every year, on the 13th of October, metastatic breast cancer awareness day is celebrated to provide support for those affected by the disease and to raise funds for research to develop improved treatment options.

What food you eat and which supplements you take is a decision you make. Your decision should include consideration of the cancer gene mutations, which cancer, ongoing treatments and supplements, any allergies, lifestyle information, weight, height and habits.

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Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.


Personalized Nutrition for Cancer!

Cancer changes with time. Customize and modify your nutrition based on cancer indication, treatments, lifestyle, food preferences, allergies and other factors.

Scientifically Reviewed by: Dr. Cogle

Christopher R. Cogle, M.D. is a tenured professor at the University of Florida, Chief Medical Officer of Florida Medicaid, and Director of the Florida Health Policy Leadership Academy at the Bob Graham Center for Public Service.

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