A 56-year-old Caucasian male with non-Hodgkin lymphoma is undergoing systemic chemotherapy. Vincristine is a part of the regimen, and you suspect accidental overdose of that agent. Which of the following would you most expect in this patient?

Question

A 56-year-old Caucasian male with non-Hodgkin lymphoma is undergoing systemic chemotherapy.  Vincristine is a part of the regimen, and you suspect accidental overdose of that agent.  Which of the following would you most expect in this patient?

Quizplus · Accepted Answer

Vincristine causes neurotoxicity by interfering with microtubule formation in nerve axons. Patients with vincristine toxicity most commonly complain of peripheral neuropathy, and neurotoxicity is the dose-limiting side effect (Choice A). All vinca alkaloids (vincristine, vinblastine) inhibit microtubule polymerization after binding to β-tubulin. Inhibition of microtubule formation prevents synthesis of the mitotic spindle in dividing cells. Without the mitotic spindle, replicated chromosomes are unable to align and segregate into their respective daughter cells during mitosis. This leads to failure of division and cell death. Vinca alkaloid agents are thus M-phase specific agents. (Choice B) Burning on urination and urgency may be seen with cyclophosphamide- or ifosfamide-induced hemorrhagic cystitis. (Choice C) Leg swelling and orthopnea are symptoms of congestive heart failure. Of the chemotherapeutic agents, doxorubicin, an anthracycline antibiotic and a chemotherapeutic intercalating agent, is most commonly associated CHF. (Choice D) Dry cough and exertional dyspnea may be seen with bleomycin, which is classically associated with pulmonary toxicity. Bleomycin specifically causes a progressive pulmonary fibrosis that can lead to death in a minority of patients. (Choice E) Tarry stool and fatigue may be seen with any chemotherapeutic agent that affects rapidly-dividing cells, but are most classically associated with alkylating agents. These agents cause death in both the rapidly-dividing tumor cells, and in other groups of cells that have a high turn-over rate, like hair, skin, and the mucosa of the GI system. Tarry stool, also called melena, is most commonly due to an upper GI bleed. (Choice F) Abdominal pain and jaundice may be seen with mercaptopurine use. Mercaptopurine is an S-phase specific purine analogue that is associated with cholestasis and hepatitis in a fair proportion of patients. Chronic methotrexate ingestion, used in rheumatoid arthritis for anti-inflammatory purposes, is also associated with cirrhosis. Educational Objective: Neurotoxicity is the dose-limiting side effect of vincristine therapy. This toxicity results from failure of microtubule polymerization in neuronal axons. Other notable adverse effects classically associated with chemotherapeutic agents include pulmonary fibrosis and flagellate skin discoloration with bleomycin use; congestive heart failure with doxorubicin; and hemorrhagic cystitis with cyclophosphamide.

A 56-Year-Old Caucasian Male with Non-Hodgkin Lymphoma Is Undergoing Systemic