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CHAPTER 2-17: ANTINEOPLASTIC AGENTS

Susan Kim-Katz

INTRODUCTION

Other than iatrogenic errors, relatively few acute overdoses of antineoplastic drugs have been reported. However, because of the inherently cytotoxic nature of most of these agents, an overdose is more likely to be extremely serious. In this chapter, antineoplastic drugs are classified into 12 broad categories and are listed alphabetically in Table II–10. Radiologic agents are not included in this chapter, and arsenic is discussed on Arsenic.

TABLE II–10.ANTINEOPLASTIC DRUGS
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TABLE II–10. ANTINEOPLASTIC DRUGS
Drug Mechanism of Actiona Major Site(s) of Toxicityb Comments
Abiraterone acetate F (antiandrogen) En+, H+ Risk of excess mineralocorticoid activity, adrenocortical insufficiency, hypophosphatemia. Potent inhibitor of cytochrome P450. Peak level 2 hours after oral dose.
Ado-trastuzumab emtansine L C+, G+, H+, M+, N+, P+ Thrombocytopenia common. Reduction in left ventricular ejection fraction seen. Watch for hypokalemia.
Afatinib G C+, D++, G++, H+, P+, R+ Diarrhea may be severe. Two adolescents developed nausea, vomiting, asthenia, dizziness, headache, abdominal pain, and elevated amylase after ingesting 360 mg. They recovered with supportive care. Peak level at 2–5 hours after oral dose.
Aldesleukin (interleukin 2) L An++, C++, D+, En+, G+, M+, N+, P++, R++ Commonly causes capillary leak syndrome resulting in severe hypotension. Respiratory distress may be life threatening.
Altretamine A G+, M+, N+ Reversible peripheral sensory neuropathy. Pyridoxine used to prevent neuropathy during therapy. Unknown if helpful with acute overdose. Peak plasma levels at 0.5–3 hours after oral dose.
Anastrozole F (aromatase inhibitor) En+, G± High risk of osteoporosis. Acute toxic effects unlikely. Peak level within 2 hours.
Arsenic trioxide     See "Arsenic"
Asparaginase L An++, En+, G+, H++, N++, R+ A 3yo boy who received a 10-fold overdose developed hyperammonemia, increased levels of glutamic and aspartic acid, and decreased levels of glutamine and asparagine. The laboratory values returned to normal after 1 week. Repeated plasmapheresis was performed on a 48yo with fulminant hepatic failure attributed to asparaginase and recovered fully.
Axitinib G C++, D+, En+, G+, H+, M+, N+, P+ Severe hypertension, hemorrhage, thromboembolic events. Doses up to 20 mg twice daily have resulted in dizziness, hypertension, seizures, and fatal hemoptysis. Peak plasma concentration 2.5–4.1 hours after oral dose.
Azacitidine D En+, G++, H+, M++, N+, R+ One patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose.
BCG (intravesical) L G+ Attenuated Mycobacterium bovis. Bladder irritation, flulike symptoms common. Risk for sepsis in immunocompromised patients.
Bendamustine A An+, D++, G+, M++ Potentially fatal dermatologic reactions. Watch for tumor lysis syndrome. Of 4 patients treated at maximum single dose of 280 mg/m2, 3 showed ECG changes, including QT prolongation, ST-segment and T-wave deviations, and left anterior fascicular block.
Bevacizumab I C++, G+, M+, N+,P+, R+ Severe and fatal hemorrhages, including Gl perforation, wound dehiscence, hemoptysis, up to 5 times more frequent ...

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