Chemotherapy is the mainstay of cancer treatment and the first line therapy of choice for most cancers as supported by clinical guidelines and evidence. However, despite the medical advancements and improvement in the number of cancer survivors over the last few decades, the short term and long term side-effects of chemotherapy remain as a major concern for both patients and clinicians. Choosing the right nutrition and nutritional supplements can help alleviate some of these side-effects.
What is Chemotherapy?
Chemotherapy is a type of cancer treatment which uses drugs to destroy the rapidly dividing cancer cells. It is also the first line therapy choice for most cancers as supported by clinical guidelines and evidence.
Chemotherapy was not originally meant for its current usage in cancer treatment. In fact, it was discovered during the second World War when the researchers realized that nitrogen mustard gas killed off a large number of white blood cells. This prompted further research on whether it could stop the growth of other rapidly dividing and mutating cancer cells. Through more research, experimentation, and clinical testing, chemotherapy has evolved into what it is today.
Different chemotherapy drugs have distinct mechanisms of action used for targeting specific cancer types. These chemotherapy drugs are prescribed :
- either before surgery to shrink the size of a large tumor;
- to just generally slow the growth of the cancer cells;
- to treat cancer that has metastasized and spread through different parts of the body; or
- to eliminate and clean out all the mutated and rapidly growing cancer cells to prevent further relapse in the future.
Today, there are more than 100 chemotherapy drugs approved and available in the market for different types of cancers. The different categories of chemotherapy drugs include alkylating agents, antimetabolites, plant alkaloids, antitumor antibiotics and topoisomerase inhibitors. The oncologist takes a decision on which chemotherapy drug to be used for the treatment of a cancer patient based on various factors. These include:
- type and stage of the cancer
- location of the cancer
- existing medical conditions of the patient
- patient’s age and general health
Despite the medical advancements and improvement in the number of cancer survivors over the last few decades, the side-effects of anti-cancer chemotherapy remain a major source of concern for both patients and clinicians. Depending on the type and extent of the treatment, chemotherapy can cause mild to severe adverse side-effects. These side-effects can greatly impact the quality of life of the cancer patient.
Short Term Side-Effects
Chemotherapy mostly damages the cells that are fastly dividing. Different parts of our body where the normal healthy cells divide frequently are likely to be most affected by chemotherapy. Hair, mouth, skin, intestines and bone marrow are commonly affected by chemotherapy drugs.
The short term side-effects of chemotherapy seen in cancer patients include :
- hair loss
- nausea and vomiting
- loss of appetite
- constipation or diarrhea
- breathing trouble
- skin changes
- flu-like symptoms
- esophagitis (swelling of the esophagus leading to swallowing difficulties)
- mouth sores
- kidney and bladder problems
- anemia (reduced number of red blood cells)
- blood clotting problems
- increased bleeding and bruising
- neutropenia (condition due to low level of neutrophils, a type of white blood cells)
These side-effects can vary from person to person and from chemo to chemo. For the same patient, the side-effects may also vary throughout the course of their chemotherapy. Most of these side-effects affect the physical as well as the emotional well-being of the cancer patients.
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Long Term Side-Effects
With the extensive use of chemotherapy treatments in different groups of cancer patients, the toxicities associated with these well-established chemotherapies such as platinum-based chemotherapies continue to increase. Hence, despite all the medical advances, most of the cancer survivors end up dealing with long term side-effects of these chemotherapy treatments, even several years after the therapy. As per the National Pediatric Cancer Foundation, it is estimated that more than 95% of childhood cancer survivors will have a significant health-related issue by the time they are 45 years old, which could be a consequence of their earlier cancer treatment (https://nationalpcf.org/facts-about-childhood-cancer/).
Different clinical studies have been carried out on cancer patients and survivors of different cancer types such as breast cancer, prostate cancer and lymphoma to evaluate the risk of long term side-effects of their cancer treatments. Clinical studies evaluating these chemotherapy side-effects in cancer survivors are summarized below.
Studies on Long term Side-Effects of Chemotherapy
Risk of Second Cancers
With the modern treatment of cancer using chemotherapy or radiotherapy, though the survival rates of solid tumors have improved, the risk of treatment-induced secondary cancers (one of the long term chemotherapy side-effects) has also increased. Different studies show that excessive chemotherapy treatments increase the risk of getting a second cancer after being cancer-free for sometime.
A study done by the National Cancer Institute closely analyzed data on over 700,000 patients with solid cancer tumors. These patients initially underwent chemotherapy from 2000-2013 and survived for at least 1 year after diagnosis. They were aged between 20 and 84. The researchers found that the risk of therapy related myelodysplastic syndrome (tMDS) and acute myeloid leukemia (AML) “increased from 1.5-fold to over 10-fold for 22 of the 23 solid cancer types investigated”. (Morton L et al, JAMA Oncology. Dec. 20, 2018)
Another study was recently done by researchers from the University of Minnesota Medical School in over 20,000 childhood cancer survivors. These survivors were first diagnosed with cancer when they were less than 21 years old, between 1970-1999 and were treated with chemotherapy/radiotherapy or chemotherapy along with radiation therapy. The study revealed that survivors who were treated with chemotherapy alone, especially those who were treated with higher cumulative doses of platinum and alkylating agents, had a 2.8-folds increased risk of subsequent malignant cancer compared with the general population. (Turcotte LM et al, J Clin Oncol., 2019)
Another research study was also carried out and published in 2016 which evaluated data from 3,768 female childhood leukemia or sarcoma cancer survivors without a history of chest radiotherapy. The cancer survivors were previously treated with increasing doses of cyclophosphamide or anthracyclines. The study found that these survivors were significantly associated with a risk of developing breast cancer. (Henderson TO et al., J Clin Oncol., 2016)
In a different study, it was found that people with Hodgkin’s Lymphoma are at a much greater risk of developing a second cancer after radiotherapy. Hodgkin’s Lymphoma is a cancer of the lymphatic system which is a part of the body’s immune system. (Petrakova K et al, Int J Clin Pract. 2018)
Also, while there is a much higher initial success rate for females with breast cancer, the risk of developing second primary malignant tumors post therapy has also increased greatly (Wei JL et al, Int J Clin Oncol. 2019).
These studies establish that childhood cancers which are treated with higher cumulative doses of chemotherapy such as cyclophosphamide or anthracyclines face an increased risk of long term side-effect of developing subsequent cancers.
Risk of Heart Diseases
Another side-effect of chemotherapy is cardiovascular or heart disease. Different studies indicate that there is an increased risk of heart failures in breast cancer survivors, years after the initial diagnosis and treatment of their cancer. Congestive heart failure is a chronic condition that occurs when the heart is unable to pump blood around the body properly.
In a recent study, Korean researchers examined the frequency of occurrence and risk factors associated with congestive heart failure (CHF) in breast cancer patients who survived more than 2 years after the cancer diagnosis. The study was conducted with the National Health Information Database of South Korea and included data from a total of 91,227 breast cancer survivor cases between 2007 and 2013. The researchers found that :
- risks of congestive heart failure were higher in breast cancer survivors, especially in younger survivors aged less than 50 years, than controls.
- cancer survivors who were previously treated with chemotherapy drugs like anthracyclines (epirubicin or doxorubicin) and taxanes (docetaxel or paclitaxel) showed a significantly higher risk of heart diseases (Lee J et al, Cancer, 2020).
In a different study done by Paulista State University (UNESP), Brazil, the researchers evaluated the risk factors associated with heart problems in postmenopausal breast cancer survivors. They compared data from 96 postmenopausal breast cancer survivors who were aged more than 45 years with 192 postmenopausal women who did not have breast cancer. The study concluded that postmenopausal women who are survivors of breast cancer had a stronger association with risk factors for heart disease and increased abdominal obesity compared to postmenopausal women without a history of breast cancer (Buttros DAB et al, Menopause, 2019).
In a study published by Dr Carolyn Larsel and team from Mayo Clinic, United States, they analyzed data from 900+ breast cancer or lymphoma patients from Olmsted County, United States. The researchers found that breast cancer and lymphoma patients were at significantly increased risk of heart failures after the first year of diagnosis which persisted up to 20 years. The study also found that patients treated with Doxorubicin had double the risk of heart failure compared to other treatments. (Carolyn Larsen et al, Journal of the American College of Cardiology, March 2018)
These findings establish the fact that some cancer therapies can increase the risk of side-effects of developing heart problems in different cancer survivors even several years after the diagnosis and treatment.
Risk of Lung Diseases
Lung diseases or pulmonary complications are also established as an adverse long term side-effect of chemotherapy. Different studies indicate that childhood cancer survivors have a higher incidence of lung diseases/complications like chronic cough, asthma and even recurrent pneumonia as adults and the risk was greater when treated with radiation at a younger age.
In a study published by the American Cancer Society, the researchers analyzed data from a Childhood Cancer Survivor Study which surveyed individuals who had survived at least five years after a childhood diagnosis of cancers such as leukemia, central nervous system malignancies and neuroblastomas. Based on data from over 14,000 patients, the researchers found that by the age of 45 years, the cumulative incidence of any pulmonary condition was 29.6% for cancer survivors and 26.5% for their siblings. They concluded that the pulmonary/lung complications are substantial among adult survivors of childhood cancer and can affect daily activities. (Dietz AC et al, Cancer, 2016).
In another study done by the researchers from Columbia University in New York, they carried out a similar assessment based on data from 61 children who underwent lung radiation and had undergone a pulmonary function test. They found a direct correlation showing that pulmonary/lung dysfunction is prevalent among pediatric cancer survivors who receive radiation to the lung as part of their treatment regimen. The researchers also observed that there was a greater risk of developing pulmonary/lung dysfunction when the treatment was done at a younger age due to the developmental immaturity (Fatima Khan et al, Advances in Radiation Oncology, 2019).
Knowing the risks of aggressive treatments like chemotherapy, the medical community can further optimize the cancer treatments in children to avoid these adverse side-effects in future. The signs of pulmonary complications should be monitored closely and steps should be taken to prevent them.
Risk of Subsequent Stroke
Examination of data from a number of independent clinical studies indicate that cancer survivors who have undergone radiation therapy or chemotherapy treatments may have an increased risk of side-effects of subsequent stroke.
In a study done by the researchers in South Korea, they examined data of 20,707 cancer patients from the Korean National Health Insurance Service National Sample Cohort database between 2002-2015. They found a positive association of a higher risk of stroke in cancer patients when compared to non-cancer patients. Chemotherapy treatment was independently associated with an increased risk of stroke. The risk was higher in patients with cancers of the digestive organs, respiratory cancers and others such as breast cancer and cancers of male and female reproductive organs. The study concluded that the risk of stroke in cancer patients increased at 3 years after the diagnosis and this risk continued until 7 years of follow-up. (Jang HS et al, Front. Neurol, 2019)
A study by Xiangya School of Public Health, Central South University, China, did a meta-analysis of 12 shortlisted independent retrospective published studies between 1990 to 2017, with 57,881 total patients, who were treated with radiation therapy. The analysis revealed a higher overall risk of subsequent stroke in cancer survivors who were given radiation therapy compared to those who were not treated with radiation therapy. They found that the risk was higher in radiotherapy treated patients with Hodgkin’s lymphoma and head, neck, brain or nasopharyngeal cancers. This association of radiation therapy and stroke was found to be higher in patients younger than 40 years when compared to the older patients. (Huang R, et al, Front Neurol., 2019).
Findings from these clinical studies have revealed a higher risk of subsequent stroke in cancer survivors who were once treated with radiation therapy or chemotherapy.
Risk of Osteoporosis
Osteoporosis is yet another long term side-effect seen in cancer patients and survivors who have received treatments like chemotherapy and hormone therapy. Osteoporosis is a medical condition in which the bone density is reduced, making the bone weak and brittle. Many studies show that patients and survivors of cancer types like breast cancer, prostate cancer and lymphoma are at an increased risk of osteoporosis.
A study led by the researchers from Johns Hopkins Bloomberg School of Public Health, Baltimore, United States, evaluated the rate of incidence of bone-loss conditions such as osteoporosis and osteopenia in 211 breast cancer survivors. These breast cancer survivors were diagnosed with cancer at a mean age of 47 years. The researchers compared the data from breast cancer survivors with 567 cancer-free women. The analysis found that there was 68% higher risk of osteoporosis in breast cancer survivors as compared to cancer-free women.The results were prominent in those treated with aromatase inhibitors alone, or a combination of chemotherapy and aromatase inhibitors or Tamoxifen. (Cody Ramin et al, Breast Cancer Research, 2018)
In another clinical study, data from 2589 Danish patients who were diagnosed with diffuse large B-cell lymphoma or follicular lymphoma were analyzed. The lymphoma patients were mostly treated with steroids like prednisolone between 2000 and 2012. The data from cancer patients were compared with 12,945 control subjects to evaluate the incidences of bone-loss conditions such as osteoporotic events. The analysis found that lymphoma patients had an increased risk of bone-loss conditions compared to control, with the 5-year and 10-year cumulative risks reported as 10.0% and 16.3% for lymphoma patients compared to 6.8% and 13.5% for control. (Baech J et al, Leuk Lymphoma., 2020)
These findings suggest that cancer patients and survivors who have received treatments such as aromatase inhibitors, chemotherapy, hormone therapy like Tamoxifen or a combination of these, are at an increased risk of bone-loss conditions.
Management of Side-Effects by selecting the Right Nutrition/Nutritional Supplements
Some of the side-effects of chemotherapy can be effectively reduced or managed by taking the right nutrition/nutritional supplements along with the treatment. Supplements and foods, if scientifically chosen, may improve the chemotherapy responses and reduce their side-effects in cancer patients. However, random selection of nutrition and nutritional supplements can worsen the side-effects.
Different clinical studies/evidences which supported the benefits of a specific food/supplement in reducing a specific chemo side-effect in a particular cancer type are summarized below.
- A phase II clinical study conducted by the researchers at Shandong Cancer Hospital and Institute in China concluded that EGCG supplementation may reduce swallowing difficulties/esophagitis without negatively impacting the efficacy of chemoradiation or radiation therapy in esophageal cancer.(Xiaoling Li et al, Journal of Medicinal Food, 2019)
- A randomized single blind study done on head and neck cancer patients showed that compared to the control group, approximately 30% of the patients did not experience grade 3 oral mucositis (mouth sores) when supplemented with royal jelly. (Miyata Y et al, Int J Mol Sci., 2018).
- A study conducted by researchers from the Shahrekord University of Medical Sciences in Iran highlighted that lycopene can be effective in decreasing the complications due to cisplatin-induced nephrotoxicity (kidney problems) by affecting some markers of renal function. (Mahmoodnia L et al, J Nephropathol., 2017)
- A clinical study from the Tanta University in Egypt demonstrated that use of Milk Thistle active Silymarin along with Doxorubicin benefits children with acute lymphoblastic leukemia (ALL) by reducing the Doxorubicin-induced cardiotoxicity. (Hagag AA et al, Infect Disord Drug Targets., 2019)
- A single center study done by Rigshospitalet and Herlev hospital, Denmark on 78 patients found that Mannitol use in head and neck cancer patients receiving cisplatin therapy can reduce Cisplatin-induced kidney injury (Hagerstrom E, et al, Clin Med Insights Oncol., 2019).
- A study done at the Alexandria University in Egypt found that taking black seeds rich in Thymoquinone along with chemotherapy may decrease the incidence of febrile neutropenia (low white blood cells) in children with brain tumors. (Mousa HFM et al, Child’s Nervous Syst., 2017)
In summary, aggressive treatment with chemotherapy can increase the risk of developing short term and long term side-effects including heart problems, lung diseases, bone-loss conditions, second cancers and strokes even several years after the treatment. Hence, before initiating the therapy, it is important to educate cancer patients on the possible adverse effects these treatments can have on their future health and quality of life. The risk-benefit analysis of cancer treatment for children and young adults should favor treating by limiting cumulative doses of chemotherapy and consideration of alternative or more targeted therapy options to reduce the risk of severe side-effects in future. Choosing the right nutrition and nutritional supplements can also help alleviate some of these side-effects.
“What should I eat?” is the most frequently asked question to cancer dieticians and physicians. The right answer depends upon cancer type, underlying genomics, current treatments, any allergies, lifestyle information, and factors like BMI.
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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.