Chapter 74

• Drug toxicity is most often a diagnosis of exclusion.
• Dose, schedule, and drug combinations are key parameters used to determine the likelihood of drug toxicity.
• Not all toxicities are known, and drug regimens are modified constantly.
• Therapy is supportive for most chemotherapy-related toxicities.
• Pelvic and spinal irradiation potentiates the myelosuppressive effects of chemotherapeutic agents.
• Bleomycin and gemcitabine are among the causes of drug-related interstitial lung disease.
• Most cardiac events in cancer patients are related to pre-existing heart disease or direct invasion of the heart by cancer; nonetheless, drug toxicity must be considered, particularly when high-dose cyclophosphamide and anthracyclines have been administered.
• In high-dose regimens, cytosine arabinoside, ifosfamide, and methotrexate may produce dramatic central nervous system syndromes.
• Renal injury is often dose limiting for cisplatin.
• Cytokines such as interleukin-2 have a wide range of toxicities involving virtually all organ systems.
• Many commonly used chemotherapeutic agents and several recently introduced targeted anticancer agents are associated with hypersensitivity reactions.
• Thrombotic microangiopathy is associated with various chemotherapeutic agents, particularly gemcitabine and mitomycin-C.

As more intensive anticancer regimens are being used to achieve cure, an increasing number of oncology patients are admitted to ICUs for complications of treatment. Several principles about drug-induced toxicity should be kept in mind.

Drug toxicity is often a diagnosis of exclusion. The toxic reaction to an antineoplastic drug or drugs is frequently nonspecific clinically and even pathologically. Other causes always should be considered. Infection, a tumor effect, and toxicity from other drugs such as antiemetics or antibiotics frequently are elements of the differential diagnosis.

Dose, schedule, and combination make a difference. Most antineoplastic drugs are given in combination, and drugs and radiation are often combined. The toxicities of a given combination may be more severe than the effects of the individual agents would suggest. Moreover, different drug schedules, such as a continuous infusion versus a single bolus dose, may have very different spectrums of side effects for the same agent. Formerly, the dose-limiting toxicity of most agents was myelosuppression, but the introduction of colony-stimulating factors and the rapidly increasing use of autologous stem cell or marrow reinfusion for rescue after very-high-dose drug regimens have exposed a plethora of new toxicities.

Not all toxicities are known. New drugs and new combinations of drugs are being tried constantly and may be used widely before all toxicities are well characterized. Moreover, the diagnosis of drug reactions that are sporadic rather than dose-related is often difficult, particularly in cancer patients who have many symptoms regardless of treatment. The tables in this chapter list the most common or notorious toxicities and are not intended to be comprehensive.

Treatment is supportive. The importance of a diagnosis of treatment-related toxicity is generally that the offending agent can be stopped, and useless remedies or diagnostic procedures can be withheld. Only rarely is specific therapy indicated.

(See ref. 1.) A great many commonly used antineoplastic agents can ...

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