Adverse effects of antineoplastic agents

Essentials

  • Antineoplastic agents can be divided roughly into classic cytostatic/cytotoxic agents, hormonal agents, antibodies, drugs affecting signalling and other drugs. All have adverse effects, and in most cases the therapeutic window is narrow.
  • Antineoplastic agents may cause immediate, delayed or late adverse effects. Late effects may only appear several years after the end of treatment.
  • Antineoplastic agents cause adverse effects such as nausea, haematological changes, hair loss, neuropathy, damage to the myocardium, lungs, liver and kidneys, skin reactions, gastrointestinal effects and endocrinopathies.
  • Before beginning antineoplastic treatment, blood tests should be taken, at least. Depending on the drug combination, laboratory tests should be repeated regularly, at least before beginning each new cycle of treatment.
  • The adverse effects of antineoplastic drugs may to some extent be controlled by adjusting the dose and by supportive medication.
  • Most antineoplastic drugs may cause miscarriages or fetal abnormalities, so birth control counselling and contraception must be taken care of. The most aggressive treatments may cause permanent or transient infertility and premature menopause.
  • If antineoplastic medication is suspected of having adverse effects, it is important to check the patient’s medication list and to make sure that the causative drug is not given again until the case has been investigated.
  • Due to the extensive range of pharmaceutical treatments and adverse effects, it is important to investigate the case carefully, consulting experts, as necessary: to interview the patient and his/her relatives (patients often have with them material concerning their medication), to consult appropriate pharmaceutical database, the oncology unit or, during on-call hours, doctors on call at secondary or tertiary care hospitals.

Nausea

  • Different antineoplastic drugs and their combinations cause varying degrees of nausea. Some drugs do not cause more nausea than placebo, while the most problematic drugs cause nausea in almost all patients.
  • Susceptibility to nausea also depends on the patient’s age, gender, earlier susceptibility to nausea and alcohol history.
  • Acute nausea begins during drug administration or within 2–6 hours after it. With mildly emetogenic drugs metoclopramide, and with more emetogenic ones serotonin antagonists, with a substance P antagonist, as necessary, can be given before administration of the antineoplastic drug. Concomitant administration of dexamethasone can be used to increase the efficacy of the antiemetic treatment, as necessary.
  • Metoclopramide, concomitantly with dexamethasone, as necessary, is effective for prolonged or delayed nausea (beginning or continuing 2–6 days after drug administration). A serotonin antagonist, substance P antagonist and/or benzodiazepine, such as lorazepam, can be added to the regimen, as necessary.
  • Anticipatory nausea (the mere fear of nausea, smells or the sight of the hospital may be enough to initiate nausea) can be prevented by benzodiazepines, such as lorazepam. These should be started the night before or a few hours before the treatment.

Evidence Summaries

Blood cytopenias

  • Antineoplastic treatments are often associated with leucopenia, thrombocytopenia and even anaemia. These typically appear within 1–3 weeks, anaemia within a few months.
  • Neutropenia (see also below ) (Leucopenia) is associated with an increased risk of infections, which may be decreased by giving a white cell growth factor. The effect is best if the treatment is initiated within 24–48 hours after administration of the antineoplastic treatment, when the blood count is still normal. In prolonged neutropenia, a white cell growth factor may also be given later on.
  • Thrombocytopenia (Thrombocytopenia) can be treated with thrombocyte transfusion if there is an evident risk of haemorrhaging or if the patient has a simultaneous neuropenic infection. In most cases, it will be sufficient to wait for spontaneous remission.
  • Anaemia is treated with red cell transfusions. If the response is insufficient and the anaemia affects the patient’s condition, intravenous iron infusion and sometimes also erythropoietin products may be used in a patient with iron deficiency.

Evidence Summaries

Neutropenic infection

  • Patients on antineoplastic treatment, whose general condition is deteriorating, with blood values falling, the CRP level increasing and/or fever, can be considered to have a neutropenic infection until otherwise proven.
  • Rapid initiation of treatment may be necessary.
  • The cornerstones of treatment are rapid history taking, clinical findings (such as general condition, fever, confusion vs. orientation, skin, mucosa, portals of entry, urine excretion, blood pressure, peripheral temperature), rapid blood tests with blood cultures, urine testing, administration of copious supportive fluids, and rapid initiation of intravenous broad-spectrum antimicrobial treatment.
  • A patient with a severe neutropenic infection may be confused, understate his/her symptoms and appear in better condition than he/she actually is (no fever, flushed cheeks).

Hair loss

  • Hair loss is a common adverse effect of many cytotoxic drugs. Choosing another cytotoxic drug can sometimes prevent it. Intense cooling of the scalp by using a special cooling cap during the administration of cytotoxic agents and for some time thereafter may decrease or slow down alopecia.
  • Hair is usually lost about 2–5 weeks after the first antineoplastic infusion and it usually grows back after termination of the treatment. Usually the hair will have grown back to such an extent after 3–4 months that the patient no longer needs to wear a wig.

Organ-specific damages

  • Anthracyclines (such as doxorubicin or epirubicin) cause myocardial damage and may lead to cardiac failure. Such damage is rare if the cumulative dose is kept sufficiently low. Sometimes the damage does not become apparent until after several months or years.
  • Fluorouracil and capecitabine may cause angina pectoris symptoms.
  • Drugs such as methotrexate, bleomycin, mitomycin and busulphan may damage gas exchange in the lungs. Differentiating this condition from changes caused by the cancer, such as lymphangitis carcinomatosa, and from infections may be difficult. After courses of bleomycin, care must be taken especially during anaesthesia.
  • Particularly cisplatin or high doses of iphosphamide or methotrexate may damage the kidneys.
  • Many cytostatic and cytotoxic drugs cause tissue damage if they escape from the vein. Severe damage may require surgical revision. Pain during infusion (if not caused by drug extravasation) can be alleviated by slowing the infusion rate or with an irrigating solution. Fluorouracil can cause innocent dark discoloration of the vein and the adjacent skin.
  • Some cytotoxic drugs, such as vincristine, oxaliplatin, cisplatin and taxanes, cause peripheral neuropathy, with paraesthesias, muscle pain and weakness, pain, tenderness to touch or sensitivity to cold as typical symptoms. Usually the symptoms start in the fingers.
  • Cyclophosphamide and iphosphamide in high doses cause irritation in the urinary bladder. This may be prevented with uromitexan (mesna).
  • Many antineoplastic drugs cause mucosal damage, liver dysfunction, electrolyte disturbances, functional cardiac symptoms, and allergic reactions. It is often difficult to differentiate between adverse effects of drugs, progression of the primary disease and comorbidities.
  • Some antineoplastic agents cause palmoplantar erythrodysaesthesia, i.e. erythema, pain and hypersensibility in the palmar and plantar skin of hands and feet. At its most extreme this may lead to painful ulcerations and exfoliation.
  • Gastrointestinal symptoms include stomatitis, diarrhoea and constipation.
  • Some antineoplastic agents may cause hypertension requiring treatment.
  • Immuno-oncological treatments typically cause a wide spectrum of endocrinopathies (such as hypo-/hyperparathyroidism, hypophysitis, adrenalitis or diabetes).
  • Hormonal agents may cause menopausal symptoms or decreased bone density, for example.

Evidence Summaries


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