Toxicity associated with chemotherapy can be acute or chronic.
Cells with rapid growth rates (eg, epithelium, bone marrow, hair follicles,
sperm) are very susceptible to damage, and various body systems may be affected as well.
Gastrointestinal
System.
Nausea and vomiting are the most common
side effects of chemotherapy and may persist
for as long as 24 to
48 hours after its administration. Delayed nausea and vomiting may persist for
as long as 1 week after chemotherapy.
The epithelium that lines the oral cavity
is susceptible to the effects of chemotherapy; as a result, stomatitis is
common. The entire gastrointestinal tract is susceptible to mucositis (inflammation
of the mucosal lining), and diarrhea is a common result. Antimetabolites and
antitumor antibiotics
are the major culprits
in mucositis and other gastrointestinal symptoms, including diarrhea, which can
be severe in some patients.
Hematopoietic
System
Most chemotherapeutic agents cause
myelosuppression (depression of bone marrow function),
resulting in decreased
production of WBCs (leukopenia), granulocytes (neutropenia), red blood cells
(RBCs) (anemia), and platelets (thrombocytopenia) and increased risk of
infection and bleeding.
Renal System
Chemotherapeutic agents can damage the kidneys
because of their direct effects during excretion and the accumulation of end
products after cell lysis. Cisplatin, methotrexate (Trexall, Rheumatrex), and
mitomycin are particularly toxic to the kidneys. Rapid tumor cell lysis after chemotherapy
results in increased urinary excretion of uric acid, which can cause renal
damage. In addition, intracellular contents are released into the circulation,
resulting in hyperkalemia, hyperphosphatemia, and hypocalcemia.
Hemorrhagic cystitis is a bladder toxicity
resulting from cyclophosphamide and ifosfamide therapy. Hematuria can range
from microscopic to frank bleeding with symptoms ranging from transient
irritative urination, dysuria, suprapubic pain, to life-threatening hemorrhage.
Protection of the
bladder focuses on
aggressive IV hydration, frequent voiding, and diuresis. Mesna (Mesnex) is a
cytoprotectant agent that binds with the toxic metabolites of cyclophosphamide or
ifosfamide in the kidneys to prevent hemorrhagic cystitis.
Cardiopulmonary
System
Anthracyclines
(daunorubicin and doxorubicin) are known to cause irreversible cumulative cardiac
toxicities, especially when total dosage reaches 600 mg/m2 and 550 mg/m2,
respectively. If these agents are administered in the presence of thoracic
radiation therapy or other agents with cardiotoxicity potential, their
cumulative dose limit is reduced to 450 mg/m2. Dexrazoxane (Zinecard) has been
utilized as a cardioprotectant when doxorubicin is needed in individuals who
have already received a cumulative dose of 300 mg/m2 and continuation of therapy
is deemed beneficial (Wilkes & Barton-Burke, 2007; Hogle, 2007). Cardiac
ejection fraction (volume of blood ejected from the heart with each beat) and
signs of heart failure must be monitored closely.
Bleomycin (Blenoxane), carmustine (BCNU),
and busulfan (Busulfex, Myleran) have cumulative toxic effects on lung
function, resulting in pulmonary fibrosis. Therefore, patients are monitored
closely for changes in pulmonary function, including pulmonary function test
results. Total cumulative doses of bleomycin should not exceed 400 U, and
carmustine should not exceed 1400 mg.
Capillary leak
syndrome with resultant pulmonary edema is a toxic effect of cytarabine
(DepoCyt, Tarabine) (AraC), mitomycin C, cyclophosphamide, and BCNU. Subtle
onset of dyspnea and cough may progress rapidly to acute respiratory distress
and subsequent respiratory failure
(Wilkes &
Barton-Burke, 2007).
Reproductive
System
Testicular and ovarian function can be
affected by chemotherapeutic agents, resulting in possible
sterility. Normal
ovulation, early menopause, or permanent sterility may occur. In men, temporary
or permanent azoospermia (absence of spermatozoa) may develop. Because treatment
may damage reproductive cells, banking of sperm is often recommended for men
before treatment is initiated. Patients and their partners need to be informed about
potential changes in reproductive function resulting from chemotherapy. They
are advised to use reliable methods of birth control while receiving
chemotherapy and not to assume that sterility has resulted.
Neurologic
System
Chemotherapy-induced neurotoxicity can
affect the CNS, peripheral nervous system (PNS), the
cranial nerves or a
combination; it is a dose-limiting toxicity. The blood–brain barrier can
protect the CNS and PNS from the toxic effects of most water soluble chemotherapy
agents, but neurotoxicity characterized by metabolic encephalopathy can occur
with ifosfamide, high-dose methotrexate, and cytarabine. With repeated doses,
the taxanes and plant alkaloids, especially vincristine, can cause peripheral
neurologic damage with sensory alterations in the feet and hands. These sensations
can be described as tingling, pricking, or numbness of the extremities, burning
or freezing pain, sharp, stabbing, or electric shock–like pain and extreme
sensitivity to touch. If unreported by patients or undetected, progressive
motor axon damage can lead to loss of deep tendon reflexes, with muscle
weakness, loss of balance and coordination, and paralytic ileus. Although
usually reversible, these side effects may take many months to resolve. Along
with the usual paresthesias of the hands and feet, oxaliplatin has a unique and
frightening neurotoxicity presentation that is often precipitated by exposure
to cold and is characterized by pharyngolaryngeal dysesthesia consisting of lip
paresthesia, discomfort or tightness in the back of the throat, inability to
breathe, and jaw pain. Patients receiving oxaliplatin must be instructed to avoid
drinking cold fluids or going outside with hands and feet exposed to cold
temperatures to avoid exacerbation of these symptoms. Cisplatin may cause
peripheral neuropathies and hearing loss due to damage to the acoustic nerve
(Wilkes & Barton-Burke, 2007). The ability of cytoprotectant agents to
prevent these significant neurotoxicities, including amifostine, is being
studied (Hogle, 2006; Wilkes & Barton-Burke, 2007).
Fatigue
Fatigue, a
distressing side effect for most patients that greatly affects quality of life,
can last for months after treatment. Assessment and nursing management of
fatigue are discussed in the Nursing Care of Patients With Cancer section of
this chapter. In 2006, the Oncology Nursing Society conducted an exhaustive
review of evidence-based interventions for fatigue management to provide
guidelines for nurses to effectively intervene and assist their patients (Mitchell,
Beck, Hood, et al., 2007).
