Common Side Effects Seen in Cancer Treatment
The presence of side effects from chemotherapy, targeted and immunotherapies should be expected to occur, at some point, during cancer treatment. Being able to reduce their impact and hopefully maintain initially, and ultimately restore functionality offers a focus and goal toward recovery and a continued quality of life. This article will present common ill effects from therapy and offer solutions from multiple paradigms for their reduction. Having options implies that there is no one magic approach to reducing these symptoms and being open to try whatever is needed to feel better is an important attitude to cultivate.
Alopecia (Cancer induced alopecia, or CIA)
This is a distressing symptom from a cosmetic physical appearance change as well as an individual’s inner and outer self image. Loss of hair can include the scalp, the eyelashes, eyebrows and beard. In fact, fifty percent consider it the worst symptom of their treatment! The hair follicles are extremely sensitive to therapies designed to stop cancer growth. And because at any given time ninety percent are in an active growth phase, cancer therapies hone in on rapidly growing cells including hair follicles.
Hair loss can occur from any of the multiple cancer treatments, chemotherapy, immunotherapy and targeted therapies, or from radiation to the head. Statistics suggest hair loss in patients occurs in 80% with paclitaxel, 60-100% treated with doxorubicin, 60% with cyclophosphamide and 10-50%with 5 FU and Lecovorone.
Often a significant amount is lost in the early period of chemotherapy initiation. During treatment sixty -five percent of patients experience thinning or loss and the following hair guidelines are useful to protect follicles from greater damage. Use mild organic shampoos, less frequently than usual, with gentle drying and soft brushing. Avoid trimming and the heat of a hair dryer. Some people choose to buzz the scalp but if shaving is preferred, always use an electric razor. A wig or scarf may also be the desirable option, but with hair loss, always wear sunscreen or a hat outside.
The variables that determine regrowth depend upon the treatment, doses given, frequency of treatments, and the length of time, all of which affect the regrowth process. Expect a few months post-therapy for growth to begin, and hair will often change, often being thin or fine with changes in your normal texture, color, and amount of growth. Permanent loss is considered to have occurred if there is no growth after 6 months.
Treatments
Scalp Cooling
It has been shown to be useful to reduce chemotherapy-induced alopecia. There are options available, including gel packs or FDA approved electronic cooled caps that can be rented. The caps offer a pump that circulates a cooling gel at a controlled temperature. The mechanism reduces blood flow to the scalp, preventing less chemotherapy circulating to the head and slows the rate of metabolic activity in the follicles. The pump is started prior to an infusion, continues throughout and a short while after completion. The success rate is 50-70%.
Vitamin D
The epidermal cells of the skin, hair and nails produce Vitamin D in the fibrous protein keratin found there. Topical application of this active hormone form of Vitamin D produced by the kidney is being used with success. It can cause irritation to the scalp but a study of 23 breast and gynecologic cancer patients on taxane, with hair loss, showed a 50% reduction in alopecia.
Bimatoprost
This is a drug, in drop form, that is used in glaucoma to reduce intraocular pressure. Another noted effect with use was that it increased the length of the eyelashes. Studies were done on both Japanese and Caucasian women on chemotherapy, with eyelash reduction, and proved effective in lengthening, thickening and darkening eyelashes after 4 months of treatment. It can cause eye irritation which reverses when the drug is stopped,
Platelet Rich Plasma, PRP
This procedure involves separating whole blood and using the enriched plasma, containing growth factors, that is injected in the scalp. It is an out of pocket expense with inconclusive research to support this use but it has had success with hair regrowth.
Multi Vitamins and minerals
Supplement replacement in safe recommended dosages, along with adequate protein are important to support repair and healing. There are no clinical studies of chemotherapy induced alopecia, but these are essential nutrients in often depleted people that seem logical to take.
DHA
Studies suggest that the omega 3 fatty acid, docosahexaenoic acid, can protect against CIA by reducing oxidative stress on regenerating hair follicles as demonstrated in animal models.
N-Acetyl Cysteine
In animal studies, NAC protected against CIA during treatment with a combination of cyclophosphamide and doxorubicin. There there has been no clinical double-blind studies.
Low Level Laser Therapy
Has been shown to stimulate hair growth in mice subjected to CIA, and in controlled human studies. LLLT was studied as a means to stimulate hair growth as it affected epidermal stem cells activation. Within recommended guidelines it is considered safe, but the optimum determination of wavelength, coherence and dosimetrics needs refinement for hair loss treatment after cancer therapies.
Chinese Medicine
CIA is considered Yin deficiency and/ or blood deficiency from the Chinese Medicine perspective
Yin is considered the structural components within the body while blood is derived from Yin.
Blood provides nourishment to the body by its flow, inside the blood vessels and acupuncture channels and outside the vessels in the form of body fluids that moisten tissues and joints.
There are modified versions of classic, 2000 year herbal formulas, that are used for CIA.
For blood, Si Wu Tang Jia Jian, and for Yin Deficient CIA to support the Yin of the Liver and Kidneys, Liu Wei Di Huang Wan Jia Jian. While these are fixed recipes Jia Jian means the base formulas with additions and subtractions and the formulas are modified with herbs needed to specifically help hair loss.
Cancer Associated Anemia (CRA)
In patients receiving chemotherapies or radiation the presence of anemia or low red blood cell count is seen in approximately 50% of people. A lowered number of red blood cells reduces the body’s ability to extract oxygen from the lungs and transport it throughout the body to organs, tissues and cells.
Symptoms that can occur are tiredness and fatigue, palpitations, ple or sallow skin coloration, dizziness, poor appetite, cognitive slowing and irritability and anemia also reduces the sensitivity to chemotherapy and radiation.
The development and severity of symptoms are affected by how low the hemoglobin level is, and how rapidly it occurred.
Cancer associated Anemias are multifactorial in nature and categorized by either a reduced number of red blood cells being made or by excessive amounts being lost.
The multiple causes include:
Suppression of bone marrow production directly from the therapy
Invasion by the cancer into the marrow reducing red cell production
Blood loss from surgery
Invasion into tissues by the cancer cells causing damage and blood loss
Nutritional deficiencies such as iron, folate or B12, and iron, often associated with nutritional depletion or consumption from the body’s treatment of inflammation.
Autoimmune breakdown of red blood cells called hemolytic anemia, which can be caused by chronic lymphocytic leukemia
Frequent blood draws for lab testing
Radiation
Chronic kidney failure
Treatments
Iron/B12/Folate
These supplements have a place in treating anemia only if measurements in the blood indicate they are deficient. Otherwise there are potential ill effects that can occur. These levels are easily measured. Treatment for B12 and folate can be oral supplementation but iron orally is poorly absorbed and if indicated in CRA it is commonly given by IV infusion
Erythropoietin Stimulating Agent
Natural erythropoietin is a hormone made in the kidney. Low levels of oxygen in the body are sensed and this hormone is released and messages the bone marrow to produce more red blood cells. In CIA, a synthetically produced form can be given to correct cancer induced anemia. There is concern that erythropoietin has other effects that may produce anti apoptotic responses to cancer cells or stimulate tumor growth in some cancers making it important for patients to discuss its use with their oncologist.
Chinese Medicine Treatment of Anemias
The source of Blood in Chinese medicine is based on the combination of the production of the Qi energy, from digestion interacting with essence or your stored vital substance needed for growth and development. These are supported with traditional acupuncture, primarily the organ points located lateral to the spine used in conjunction with herbal formulas.
There are multiple supportive herbal chinese formulas which are prescribed based on symptom patterns, pulse diagnosis and body palpation. Those for digestion most commonly are a complex combination with ginseng being the principle herb, while the essence formulas are represented by kidney tonics. There are also herbal formulas to restore the white blood cells and platelets.
While there are no double blind studies of these treatments, this approach to anemia in Chinese medicine has been used in Chinese medicine herbal cancer clinics for many decades with success.
Anorexia or Loss of Appetite
Cachexia
In people undergoing cancer treatment, almost half experience loss of appetite called anorexia; along with cachexia, which is the breakdown and loss of skeletal muscle mass, with muscle wasting and associated weight loss. It is often also accompanied by loss of fat mass too. It is a serious problem, and considered responsible for 30% of cancer deaths. It is resistant to treatment, using nutritional resources and appropriate dietary intake.
The problem is complex and made more difficult in that both the cancer itself and its treatment both create different effects. Aspects of cachexia and muscle wasting involve cancer’s ability to maintain its replication and continued growth by regulating and controlling cellular signaling, vascular enhancement and immune regulation, within the host, to enhance its own survival.
Effects:
Cachexia is insidious and can slowly develop early in treatment, but often occurs later with progression of disease. Treatment factors influencing it include:
The underlying inherent strength and overall level of heath of a person offers a level of protection
Chemotherapy treatment causes nausea,vomiting and diarrhea, reducing food and fluid intake and calorie absorption; examples being 5-FU, cisplatin and Irinotecan.
Chemotherapy suppresses appetite, examples being platins and cyclophosphamide
Inflammation from chemotherapy alters mitochondrial action, via cytokine activation of oxidative stress, and shifts it away from energy production. As a result muscle energy and strength is reduced, exemplified by the potential effect of diminished cardiac muscle function and potential heart failure associated with the drugs herceptin and doxorubicin.
Loss of muscle mass and strength, reduces physical activity,a known way to improve muscle mass.
Specific cancers, the colon and stomach, pancreas and lung cause greater loss of muscle mass and muscle wasting.
There are neuroendocrine interactions that decrease appetite and desire for food. This can be associated with treatment impairment of taste and smell and importantly can also be a stress response with anxiety to the disease itself.
Manipulation of neuroendocrine functions occurs that also create metabolic imbalances in the hypothalamic-pituitary-adrenal axis prompting the release of glucocorticoids that drive tissue breakdown, and intestinal Vagus nerve dysfunction can affect bowel motility and digestion.
Metabolic alterations shift the body from promotion of building and repair to breaking down tissues, resulting in shifts of pathways that promote protein breakdown. In skeletal muscle this action affords the cancer materials such as glucose, glutamine and ketones that can be utilized for energy production and results in atrophy, or loss of muscle mass and decreased strength.
Activation by the immune system of signaling via small proteins, cytokines, that promote inflammation and tissue damage from oxidative stress both of which can be generated by both the body and cancer cells. This process can promote signalling for programmed death of skeletal muscle cells.
Cancer cell growth and spread involves signalling pathways that promote cachexia.
The microbiome can contribute to cachexia via gut inflammation and immune reactions from barrier disruption.
Also, there is the intestinal production of ghrelin which activates appetite through the hypothalamus,which in cancer patients has diminished effect.
These changes in appetite leading to weight loss, diminished appetite and muscle wasting alters the person’s appearance often affecting the family dynamic. Meal time has meaning in many cultures as a time to cook, eat and interact together and is the expression of love in the family. Also, when someone becomes cachectic, thin and muscle wasted a caregiver can feel that they are not providing the necessary care their loved one deserves.
Fatigue
Fatigue is a significant complaint in cancer and is reported in the majority of patients during radiation or chemotherapy, up to 99%, and can be a persistent symptom, extending from months to years, in one quarter to one-third following treatment.
People relate to fatigue in normal day-to-day life as a transient or short-lived experience, just feeling out of sink or tired. This is distinct from the fatigue of cancer, or serious illness, as rather than a temporary inconvenience, it is persistent, unremitting and unresolved.
It also is recognized that with any level of activity there tends to be greater aggravation of the fatigue than would be expected, and rest and sleep generally do not alleviate it.
As a result there is a significant impact on the ability to enjoy life, perform everyday normal activities with family and friends, and maintain a necessary level of occupational performance, allowing fulfillment of financial responsibilities. Another effect is the common development of a change in self image and mood alterations with depression and anxiety concerning fears of future health and survival.
And yet this scenario often goes unnoticed or unrecognized as many patients don't complain of their fatigue and its consequences in their lives, often believing they have to live with it because they do not believe there are effective treatments available.
Interestingly, fatigue is a subjective description of feelings, based on both cultural background and language and as a result no testing or imaging can diagnose it. There are questionnaires that help to focus on its symptoms which in western cultures, people describe as feeling weary, tired, low energy, or exhausted and which might reference how the body feels, the emotional state or mental brightness or clarity. In other cultures asking these symptoms may not uncover the problem as often their terminology is different than the western description
Effects of Inflammation in Cancer-Related Fatigue
The result of downstream effects from therapies creates multiple imbalances and often injured systems that can contribute to fatigue. Evaluations to assess which symptoms are amenable to therapeutic interventions provide opportunities for recovery and symptom reduction.
One common foundational component of fatigue is related to the presence of chronic inflammation and associated oxidative stress.
The effects of radiation and pharmaceutical drug therapies in cancer treatment affects both cancer cells and healthy tissues. The result of the damage activates an immune response releasing proinflammatory cytokines, via white blood cells to remove this cellular associated damage. These damaged molecules, both healthy and malignant, are recognized by the immune system as what are called damage associated molecular patterns (DAMPs).
This recognition generates inflammation both in local areas and extends systemically including inflammatory cells crossing the blood brain barrier, activating the brain's immune cells, the microglia, and creating imbalance in the hypothalamic-pituitary axis initiating
Hormonal balances which control ACTH, which downregulates inflammation through cortisol.
Alterations Sleep rhythms
Lessens thyroid activity, and metabolic activity
A reduction in cognitive functions
Decreased Oxytocin which regulates social interaction and emotions affecting bonding and attraction, the love hormone
Fatigue can also increase associated with post-treatment medical problems including:
Infections can result from immune weakness secondary to therapy or from reactivation of lurking dormant pathogens especially the herpes family of viruses
Nutrient deficiencies from diminished appetite and food intake, reducing essentials needed for cellular repair and rejuvenation
Chronic low white blood counts resulting in diminished immune protection,
Sleep disturbance interfering with rest and time for repair
Hormonal imbalances
Decreased organ functions from treatment toxicity
Neuro cognitive inflammatory impairment
Psychological impacts of disease
Fatigue from medications often opioids or antidepressants
Focal neurologic problems from nerve damage
Mitochondrial damage impacting cellular energy production secondary to inflammatory generated oxidative stress
The new onset of medical problems or exacerbation of existing diseases.
There are often a combination of these issues and treatment can be limited to change fatigue. The recommendations by the American Society of Clinical Oncologists are few!
Treatments for Cancer Related Fatigue (CRF)
Integrative Studies
The American Society of Clinical Oncology (ASCO) and the American Society for Integrative Oncology (ASIO) in a paper in 5/2024 recommended evidence-based randomized controlled studies substantiate the beneficial effect and improvement in cancer related fatigue.
However, the recommendations listed below 36% of the studies were based on breast cancer exclusively,13% of patients were at the end of life, the percent women in the studies varied from 12 to 100%, with the exception of a few prostate studies. In studies that reported sex, women were 0-62% and in one third of the studies reporting populations included less than 30% ethnic or racial minority populations.
Those associated with improvement are:
Cognitive Behavioral Therapy recognizes the connections between thought, feeling and action, and identifies patterns that appear detrimental to overall well being. A person’s goals for change can be discussed and updated and methods of learning more beneficial strategies can be integrated into a person’s life.
Mindfulness Based Programs include meditation and relaxation and mindful awareness techniques that allow people to observe their feelings, thoughts and actions and remain more neutral and less reactionary when they occur.
Qigong and Tai Chi utilize a series of concise movements that incorporate mental concentration, balance and coordination, energy movement, and relaxation to induce homeostasis and integrate a mind-body connection that improves health and well being.
Yoga
Acupressure
Moxibustion
American Ginseng
They did not recommend, due to lack of controlled trials, acupuncture, massage, progressive muscle relaxation, music therapy, CoQ10, Omega 3 fatty acids or mistletoe.
However, there are studies showing the effectiveness of other integrative therapies but the sample size and number of total studies are limited, but suggest opportunities for safe non toxic modalities that might offer improvement.
CRF in Breast Cancer
Forty eight patients receiving hormonal therapies for breast cancer were randomized, to a treated group that received Ganoderma, Reishi, mushroom powder and a control group. TNF-alpha, IL6 ( inflammatory cytokines) and liver and kidney function were tested before and after treatment. Reshi is known to regulate cellular( T cell ) and humoral ( antibodies) immunity, and In this study, treatment was associated with statistical and clinical improvements of physical well being and fatigue, less anxiety and depression and improved quality of life. Also, the inflammatory markers decreased and no adverse effects occurred.
Ginseng Nutritive Herbal Formula ( Ren Shen Yang Rong Tang )
This formula is from a Chinese herbal book written in the mid twelfth century. In a 2019 study, eighty three patients, 42 controls, 41 treated. When given this formula and evaluated with the MD Anderson questionnaire on fatigue the treated group had a significant reduction in CRF from clinical and statistical perspective.
Acupuncture
There is a study that reviewed 10 randomly controlled trials which included 733 acupuncture patients and 594 controls that showed acupuncture had an effect on function in cancer patients regardless of ongoing cancer treatments, especially in breast cancer patients. Treatment indicated acupuncture can reduce CRF compared to sham acupuncture and usual care. Adverse effects were spot bleeding from a needle and bruising.
Interestingly, the points or protocols used were not mentioned.
It is important to understand that acupuncture, whether for wellness or illness, including CRF or other adverse effects of therapies, needs to account for both a person’s unique inherent strengths and weaknesses, their constitution, as well as their symptoms. This is an essential principle of practice in Chinese medicine, both the foundation, the root, and the symptoms, the branches are interconnected and must be addressed to achieve resolution. Each acupuncture visit therefore treats this combination of elements and will require modifications at each visit based on the examination and changes in signs or symptoms.
Therefore, the concept of controlled studies, with each person receiving the same treatment, as seen in western medicine, contradicts the principle of individualized unique therapies for each person.
Auricular(Ear) Acupuncture
Multiple databases were reviewed that were randomized controlled studies and their effects on CRF. Six studies which included 394 patients compared standard care with auricular acupuncture and standard care. The results indicated CRF and quality of life showed positive effects when auricular acupuncture was added to standard care. The authors however felt the results were inconclusive as there were too few studies and less rigor in the study protocols require, but recommended further studies as it was a safe treatment but needed better study design.
Other Modalities to Improve CRF
Exercise:
Exercise is one of the cornerstone therapies recommended as beneficial essential intervention to reduce cancer related fatigue. Research documents chemotherapy as well as hormonal, targeted and immunotherapies as causes of CRF, and when used in combination can increase it.
Aerobic exercise such as walking, cycling and swimming are recommended as well as the addition of resistance and flexibility training as a complement, since all can contribute to CRF reduction. Advice is generically provided for the frequency of an activity and the amount of overall time per day that is needed.
During active therapies and at their conclusion, most people are debilitated and have lost muscle mass and strength and depending on other medical conditions they may be unable to exercise at recommended levels. Attempting to do so might also result in increased fatigue, possible injury or sets up a situation that creates a sense of failure at being unable to follow the recommendations. Certainly some form of activity is better than none, but initiation must be slow with a very gradual increase in increments over time. The intention is setting the objective, and adding exercise to reduce CRF, with the potential added benefit that exercise reduces the risk of recurrence. Therefore, because of Individual variability, a one size fits all exercise plan is not possible and seeking the advice from a physical therapist or a physical trainer experienced in rehabilitation will provide the needed guidance to succeed.