Chemotherapy Side Effects and Syndromes

Original Editors -Alisha Dye & Monica Toole Students from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Lead Editors  

Definition/Description[edit | edit source]

   Chemotherapy is the use of medicines or drugs to treat a disease, such as cancer. This treatment is often referred to as “chemo.” Two other medical terms used to describe cancer chemotherapy are antineoplastic (meaning anti-cancer) therapy and cytotoxic (cell-killing) therapy. Chemotherapy differs from surgery and radiation due to the fact that it’s a systemic treatment. This means the drugs travel throughout the body to reach cancer cells wherever they are.[1] During this process, the nonspecific chemotherapeutic agents not only target the cancer cells but also affect normal cells. Chemo can kill cancer cells that have metastasized or spread to parts of the body far away from the primary tumor. [2] It is used to treat about 60% of metastatic cancers that cannot be cured by localized methods.[3]

   The first drug used for cancer chemotherapy did not start out as a medicine. During a military operation in World War II, a group of people were accidentally exposed to mustard gas and were later found to have very low white blood cell counts. Doctors then reasoned that something in the gas damaged the rapidly growing white blood cells therefore it could have a similar effect on cancer. So, in the 1940s, several patients with advanced lymphomas were given the drug intravenously, rather than by breathing the irritating gas. Their improvement, although temporary, was remarkable. That experience led researchers to look for other substances that might have similar effects against cancer. As a result, many other drugs have been developed.[1]

Chemotherapy Goals:
• Cure the cancer
• Keep the cancer from spreading
• Slow the cancer’s growth
• Kill cancer cells that may have spread to other parts of the body
• Relieve symptoms caused by cancer [2]

Prevalence[edit | edit source]

[4]
Systemic chemotherapy plays a major role in the management of the 60% of malignancies that are not curable by regional modalities. [5] It can significantly delay and interfere with cancer treatment because the presence of chemotherapy-induced side effects can warrant a dose reduction, or a delay or cessation in treatment. [6]

Characteristics/Clinical Presentation[edit | edit source]

Side Effect

Clinical Presentation

 Chemo-induced Peripheral  Neurophathy[6]

Sensory: Paresthesia, hyperesthesia, hypoesthesia, dysesthesia, pain, numbness and tingling, hyporeflexia or areflexia, diminished or absent sensation (all types),
Motor: distal muscle weakness, difficulty with fine motor skills, gait disturbances
Autonomic: constipation, urinary retention, sexual dysfunction, blood pressure alterations

"Chemo brain"

Cognitive impairment, primarily affecting verbal and visual memory, attention, concentration, language, motor skills, multitasking and ability to organize information.[7]

 Anemia

Fatigue, dizziness, paleness, shortness of breath, weakness or racing heart

 Fatigue

Mild tiredness or feeling completely wiped out that doesn’t get better with rest/sleep.  Affects 70-100% of people with cancer

 Pain

Burning, numbness, tingling (most often in the fingers or toes), headaches, muscle pains, or stomach pains

 Hair Loss

Mild or severe hair loss on arms, legs, face or scalp

 Myelosuppression  (Decreased CBC)

Unexpected bruising, red/pink urine, bloody BM, nose/gum bleeding, or dizziness

 Infection

Fever, chills, sweating, loose stools, sore throat, or abdominal pain

 Nausea/Vomiting

Usually lasts several hours after treatment; 1 in 4 cancer patients experience N&V in anticipation of chemotherapy treatment. This is likely a learned response.[12]

 Constipation

No BM in 2 or more days

 Diarrhea

2 or more loose stools in 4 hours

 Mouth/Gum/Throat  Problems

Sores, dryness, bleeding, or irritation  

Nervous System

Loss of balance, clumsiness, hearing loss, vision changes, neuropathies, cognitive impairment
 Musculoskeletal 

Jaw pain, muscle weakness, joint pain, low BMD[3]

 Skin/Nail Changes

Color changes, redness, itching, peeling, dryness, rashes or acne

 Bladder/Kidney Problems

Pain when urinating, frequent urination, bloody urine, fever or chills

 Cardiotoxicity

Reversible or permanent damage to the myocardium[3]

 Pulmonary Toxicity

Bronchospasm, pneumonitis, acute lung injury[3]

Hepatic Toxicity

Steatosis, chemo-induced steatohepatitis, sinusoidal injury[3]

Reproductive

Sterilixation, sexual dysfunction[3]

Weight Changes

Weight gain or loss[3]

[2],[3]


More information about most prevalent chemotherapy side effects in detail:

  1. Chemo-induced Peripheral Neuropathy (CIPN): It is estimated that the prevalence of peripheral neuropathy is 3-7% in patients with single chemotherapy agents and around 38% in patients with multiple chemotherapy agents. However it is difficulty to be certain about the prevalence due to a lack of diagnostic criteria and a standard mechanism of measuring and reporting. Much research about treatment for CIPN is derived from studies for the treatment of diabetic neuropathy and HIV-induced neuropathy. The most common chemotherapy agents that cause peripheral neuropathy are platinum compounds, taxanes, vinca alkaloids, thalidomide, and bortezomib[6]
  2. "Chemo-brain": Affects about 1/3 of patients. It is associated more with higher dosages of chemotherapy agents. Treatment to prevent or reverse "chemo-brain" includes reorganizing home and work environment, memorization exercises, the use of mnemonic devices, notes, avoidance of distractions, and possibly medications[7]


Associated Co-morbidities[edit | edit source]

     The most common pre-existing condition observed in all patients with cancer is hypertension. Diabetes is the second most prevalent pre-existing condition in middle-aged patients, however a previous solid tumor is the second most common pre-existing condition in patients 74 years of age or older.

Other comorbidities that may occur with cancer include:

  • Obesity
  • Digestive system disease
  • Arthritis
  • Dementia
  • Thrombotic conditions
  • Depression
  • Chronic obstructive pulmonary disease (COPD)
  • Osteoporosis [5]

Chemotherapy Agents[edit | edit source]

1. Alkylating agents: These directly damage DNA to prevent the cancer cell from reproducing. These agents work in all phases of the cell cycle. Alkylating agents commonly treat leukemia, lymphoma, Hodgkin disease, multiple myeloma, sarcoma, and cancers of the lung, breast, and ovary. Because these drugs damage DNA, they can cause long-term damage to the bone marrow. There are different classes of alkylating agents, including: Oxaliplatin, Nitrogen mustards, Nitrosoureas, Alkyl Sulfonates, Triazines, and Ethylenimines.

 2. Antimetabolites: This is a class of drugs that interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA. They are commonly used to treat leukemias, breast and ovary cancers. Examples include: Capecitabine, Cladribine, Clofarabine, Cytarabine, Floxuridine, Fludarabine, Gemcitabine, Hydroxyurea, Methotrexate, Pemetrexed, Pentostatin, and Thioguanine.

3. Anthracyclines: These anti-tumor antibiotics interfere with enzymes involved in DNA replication and are used for a variety of cancers. These drugs work in all phases of the cell cycle. A major consideration when giving these drugs is that they can permanently damage the heart if given in high doses. Because of this, lifetime dose limits are often placed on these drugs. Examples include: Daunorubicin, Doxorubicin, Epirubicin and Idarubicin.

4. Mitoxantrone: This anti-tumor antibiotic also interferes with enzymes involved in DNA replication. This drug also has potential for damaging the heart and can lead to treatment-related leukemia. Mitoxantrone is used to treat prostate cancer, breast cancer, lymphoma, and leukemia.

5. Topoisomerase inhibitors: These drugs interfere with enzymes called topoisomerases, which help separate the strands of DNA so they can be copied. They are used to treat certain leukemias, as well as lung, ovarian, gastrointestinal, and other cancers. Examples include: Topotecan, Airinotecan, Etoposide and Teniposide.

6. Mitotic inhibitors: These medications are often plant alkaloids and other compounds derived from natural products. They can stop mitosis or inhibit enzymes from making proteins needed for cell reproduction. They are used for breast and lung cancer, myelomas, lymphomas, and leukemias. These drugs are known for their potential to cause peripheral nerve damage. Examples include: Taxanes, Epothilones, Vinca alkaloids, and Estramustine.

7. Corticosteroids: Steroids are hormone-like drugs that are useful in treating cancer including lymphoma, leukemias, and multiple myeloma. Corticosteroids are also commonly used as anti-emetics to help prevent nausea and vomiting caused by chemotherapy. They are also used before chemotherapy to help prevent severe allergic reactions. When a corticosteroid is used to prevent vomiting or allergic reactions, it’s not considered chemotherapy. Examples include: Prednisone, Methylprednisolone, and Dexamethasone

Diagnostic Tests/Lab Tests/Lab Values[edit | edit source]

Complete Blood Counts

CBCs are routinely performed during chemotherapy to check the number of each type of blood cell circulating in the body.

Red blood cells (RBC)
Men: 4.5 to 6.2 million per drop
Women: 4.2 to 5.4 million per drop

White blood cells (WBC)
Men and Women: 3,700 to 10,000 per drop
Lowest level at which someone is safe from infection: 1,000

Platelets
Men and Women: 150,000 to 450,000 per drop
Lowest level at which someone's blood can still clot normally: 100,000
Level at which there's a risk of spontaneous bleeding: 50,000
Level at which bleeding can become life-threatening: 5,000[1]


OnPART

This diagnostic test was designed to determine an individual’s risk of developing side effects associated with chemotherapy based on their genomic profile. The preliminary results of a clinical study of OnPART were recently reported by the company at the annual meeting of the Multinational Association of Supportive Care in Cancer. In this study, OnPART correctly identified patients at risk for chemotherapy-induced diarrhea (CID) with an accuracy of 96.7%. This diagnostic test is expected to be commercially available in 2014.[2]

Etiology/Causes[edit | edit source]

None.

Systemic Involvement[edit | edit source]

Respiratory System
Patients receiving chemotherapy are at risk for developing infection, metastatic disease, pulmonary embolism, or drug-induced pulmonary toxicity. Chemo drugs commonly cause pulmonary toxicity but many other drugs may also have an association. Initial presentation can be hard to detect because the patient may be asymptomatic and changes on chest X-ray may be minimal. However, patients may complain of a dry cough or increasing breathlessness with exercise. Due to the immunosuppressant effects of chemotherapy drugs, patients may also present with infections such as pneumonia.

Cardiovascular System
Cardiac toxicity due to chemotherapy is common and may be life threatening or cause significant morbidities. Common symptoms include hypotension, hypertension, arrhythmias, myocardial infarction, congestive cardiac failure, cardiomyopathy, myocarditis, and pericarditis, leading to pericardial effusion and cardiac tamponade. Cardiac toxicity can be immediate or delayed after completion of the course of chemotherapy.

Chemotherapy drugs tend to damage myocytes, cardiac valves, vessels and the pericardium. Risk factors for cardiotoxicity include pre-existing cardiac disease, the use of concurrent chemotherapy agents, older than the age of 70, female, and current or previous radiation therapy involving the mediastinum.

Renal System
Several chemotherapy drugs can cause acute or chronic renal failure. Common chemotherapy drugs are often a cause of renal tubular and glomerular damage. Most commonly, these medications cause: proximal tubular abnormality, hemorrhagic cystitis, microangiopathic hemolytic anemia and renal failure.

Nervous System
Chemotherapy can damage any part of the nervous system. Chemotherapy agents can cause neurotoxicity, peripheral neuropathy, muscle pain, cranial neuropathy, seizures or exacerbate pre-existing neurological conditions. There are also effects on the autonomic nervous system, which can cause orthostatic hypotension. In high-doses some drugs may induce acute encephalopathy, causing confusion, seizures, hemiparesis, and coma. It is important that physical therapists conduct a full neurological examination to detect any neurological damage.

Gastrointestinal
Gastrointestinal toxicity is a common side effect of most chemotherapy drugs. Signs and symptoms of gastrointestinal toxicity includes: nausea and vomiting, mucositis, diarrhea and dehydration. It is important that fluid and electrolytes are replenished before and after exercise.[3]

Medical Management (current best evidence)[edit | edit source]

Dosage 

Depending on the drug given, there are different ways to determine chemotherapy doses. The overall dose may be based on a person’s body weight or can be determined based on body surface area, which is calculated using the patient’s height and weight.

Dosage considerations include:

  • Age
  • Nutritional status
  • BMI
  • Previous or current medications
  • Previous or current radiation therapy
  • Blood cell count
  • Liver and kidney function

Cycle

Chemotherapy is generally given at regular intervals called cycles. A chemotherapy cycle may involve a dose of one or more drugs followed by several days or weeks without treatment. This gives normal cells time to recover from the drug’s side effects. Sometimes, doses may be given several days in a row, or every other day for several days, followed by a period of rest. Some drugs work best when given continuously over a set number of days.

Cycle considerations include:

  • Minimizing side effects
  • Number of drugs being used
  • Type of cancer
  • Stage of cancer
  • Health status
  • Goals of treatment

It's important, when possible, to get the full course of chemotherapy and to keep the cycles on schedule. This will give you the best chance to get the maximum benefit from treatment.[4] 

Physical Therapy Management (current best evidence)[edit | edit source]

It is extremely important to take a client history of current chemotherapy dosages and to monitor the hematologic values in clients receiving physical therapy. Current guidelines recommend that individuals undergoing chemotherapy should not exercise within two hours of their treatment because the increase in blood circulation during exercise may change the effects of the chemotherapy treatment. The suggested two hour delay is reasonable given the half- life of most chemotherapeutic agents.

Contraindications to Exercise

Platelet count

<20,000/ml: Consult MD 
<30,000/ml: Bedside, gentle AROM
<50,000/ml: Avoid resisted exercise

Hemoglobin <10 g/dl
WBC <5,000/ml with fever
Hematocrit <25%


Physical Therapy Implications

  • Strength
  • Balance
  • Endurance
  • Range of motion
  • Coordination
  • Quality of life
  • Energy Conservation
  • Integumentary education
  • Infection education

According to a study by Dimeo et al, a six week endurance training program of low to moderate levels of aerobic exercise showed significant improvements in physical performance and temperament while reducing mental stress and fatigue when undergoing chemotherapy. [5]

Other Management Strategies(current best evidence)[edit | edit source]

Acupuncture: Studies show acupuncture may be helpful in relieving nausea and may also help relieve certain types of pain in people receiving chemotherapy. 

Aromatherapy: Aromatherapy uses fragrant oils to provide a calming sensation which may be helpful in relieving nausea, pain and stress. 

Biofeedback: Biofeedback may be helpful in relieving pain in people with cancer.

Exercise: Exercise may help you manage signs and symptoms during and after cancer treatment. Gentle exercise, such as walking or swimming, may help relieve fatigue and stress and help you sleep better.

Hypnosis: Hypnosis may be helpful for people with cancer who are experiencing anxiety, pain and stress. It may also help prevent anticipatory nausea and vomiting that can occur if chemotherapy has made you sick in the past.

Massage therapy: Studies have found massage can be helpful in relieving pain in people with cancer. It may also help relieve anxiety, fatigue and stress.

Meditation: Meditation may help people with cancer by relieving anxiety and stress.

Music therapy: Music therapy may help relieve pain and control nausea and vomiting.

Relaxation techniques: Relaxation techniques may be helpful in relieving anxiety and fatigue and they may also help people with cancer sleep better.

Tai chi: Practicing tai chi may help relieve stress.

Yoga: Yoga may provide some stress relief for people with cancer. Yoga has also been shown to improve sleep and reduce fatigue.

Some alternative treatments have been shown to work well together but more research is needed for conclusive evidence. [6]

Differential Diagnosis[edit | edit source]

None

Case Reports/ Case Studies[edit | edit source]

Hypnosis in the Prevention of Chemotherapy-Related Nausea and Vomiting in Children: A Prospective Study
Jacknow DS, Tschann JM, Link MP, Boyce TW. Hypnosis in the Prevention of Chemotherapy-Related Nausea and Vomiting in Children: A Prospective Study. J of Developmental & Behavioral Pediatrics. 1994;15(4):258-264.

Chinese Medical Herbs for Chemotherapy Side Effects in Colorectal Cancer Patients
Wu T, Munro AJ, Guanjian L, Liu GJ. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. The cochrane library. 2008;4.

Cognitive Distraction and Relaxation Training for the Control of Side Effects Due to Cancer Chemotherapy

Vasterling J, Jenkins RA, Tope DM, Burish TG. Cognitive distraction and relaxation training for the control of side effects due to cancer chemotherapy. Journal of Behavorial Medicine. 1993; 16(1):65-80.

On the Receiving End-Patient Perception of the Side-Effects of Cancer Chemotherapy

Coates A, Abraham S, Kaye SB, et al. On the receiving end-patient perception of the side-effects of cancer chemotherapy. European Journal of Cancer and Clincal Oncology. 1983; 19(2):203-208.

Resources
[edit | edit source]

 American Cancer Society [7] 

Cancer Care [8]

OncoLink [9]

Recent Related Research (from Pubmed)[edit | edit source]

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References[edit | edit source]

see adding references tutorial.

  1. Haiken M. How blood test results can affect chemotherapy [Internet]. 2007 [cited 2013 Mar 26]. Available from: http://www.caring.com/articles/chemotherapy-blood-test-results
  2. Diagnostic test could determine a patient's risk for debilitating chemotherapy-related side-effects [Internet] 2012 Jul 3 [cited 2013 Mar 26]. Available at: http://northend.patch.com/announcements/diagnostic-test-could-determine-a-patients-risk-for-debilitating-chemotherapy-related-side-effects
  3. Medscape [Internet]. Anaesthetic implications of chemotherapy; 2012 [cited 2013 Mar 26]. Available from: http://www.medscape.com/viewarticle/760766_4
  4. Cite error: Invalid <ref> tag; no text was provided for refs named two
  5. Cite error: Invalid <ref> tag; no text was provided for refs named book
  6. Alternative cancer treatments: 11 options to consider [Internet]. Mayo Clinic; 19 Jan 2012 [cited 2 April 2013]. Available from: http://www.mayoclinic.com/health/cancer-treatment/CM00002/METHOD=print
  7. Cite error: Invalid <ref> tag; no text was provided for refs named one
  8. Chemotherapy [Internet]. 2013 [cited 2013 Mar 26]. Available from: www.cancercare.org/tagged/chemotherapy
  9. Chemotherapy [Internet]. 1994 [updated 2013; cited 2013 Mar 26]. Available from: http://www.oncolink.org/treatment/treatment1.cfm?c=2

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