What are the side effects of Vincristine (Oncovin)?

Vincristine Side Effects

Vincristine causes significant neurotoxicity as its primary and most troublesome adverse effect, along with gastrointestinal complications, hematologic effects, and less commonly cardiovascular and hepatic toxicity. 1

Neurologic Side Effects (Most Common and Dose-Limiting)

Peripheral Neuropathy

• Peripheral neuropathy is the most common and dose-limiting toxicity, typically presenting in a "glove and stocking" distribution with sensory impairment, paresthesias, and mechanical allodynia 2, 1
• Neurotoxicity follows a predictable sequence: initially sensory impairment and paresthesias, followed by neuritic pain, and finally motor difficulties with continued treatment 1
• Loss of deep-tendon reflexes, foot drop, ataxia, and paralysis occur with continued administration 1
• Neuropathy affects 92% of patients receiving full-dose vincristine, with WHO Grade 3 peripheral neurotoxicity occurring in 15% of patients 3
• Motor symptoms in severe cases can progress to limiting self-care and requiring aids for walking 2

Cranial Nerve Manifestations

• Isolated paresis and/or paralysis of muscles controlled by cranial motor nerves can occur, with extraocular and laryngeal muscles most commonly involved 1
• Potentially life-threatening bilateral vocal cord paralysis may occur even in the absence of motor impairment elsewhere 1
• Vestibular and auditory damage to the eighth cranial nerve can cause partial or total deafness (temporary or permanent), dizziness, nystagmus, and vertigo 1
• Transient cortical blindness and optic atrophy with blindness have been reported 1

Central Nervous System Effects

• Convulsions, frequently with hypertension, have been reported, with several instances of convulsions followed by coma in pediatric patients 1
• Acute encephalopathy and fulminant encephalopathy are extremely rare but documented complications 4

Pain Syndromes

• Jaw pain, pharyngeal pain, parotid gland pain, bone pain, back pain, limb pain, and myalgias can be severe 1

Autonomic Dysfunction

• Constipation, postural hypotension, bladder disturbances, and reduced heart rate variability are common autonomic manifestations 2

Gastrointestinal Side Effects

Constipation and Ileus

• Constipation is extremely common and may take the form of upper-colon impaction with an empty rectum on physical examination 1
• A routine prophylactic regimen against constipation is recommended for all patients receiving vincristine 1
• Paralytic ileus (which mimics the "surgical abdomen") may occur, particularly in young pediatric patients, and reverses with temporary discontinuance and symptomatic care 1
• Constipation occurs in 10% of patients at WHO Grades 3-4 severity 3

Other Gastrointestinal Effects

• Abdominal cramps, weight loss, nausea, vomiting, oral ulceration, diarrhea, intestinal necrosis and/or perforation, and anorexia have occurred 1

Hematologic Side Effects

• Vincristine does not typically cause significant bone marrow depression as a major dose-limiting event, unlike other chemotherapy agents 1
• However, anemia, leukopenia, neutropenia, and thrombocytopenia have been reported 1
• In combination regimens, neutropenia rates range from 38.2% to 65.7% depending on the specific combination used 5

Cardiovascular Side Effects

• Hypertension and hypotension have occurred 1
• Vincristine combinations given to patients previously treated with mediastinal radiation have been associated with coronary artery disease and myocardial infarction, though causality has not been established 1
• Chronic treatment causes functional alterations in vascular function of both conductance and resistance vessels, with significant endothelial dysfunction 6

Hepatic Side Effects

• Hepatic veno-occlusive disease has been reported in patients receiving vincristine, particularly in pediatric patients, as part of standard combination chemotherapy regimens 1
• Some patients had fatal outcomes; some survivors underwent liver transplantation 1

Genitourinary Side Effects

• Polyuria, dysuria, and urinary retention due to bladder atony have occurred 1
• Other drugs causing urinary retention should be discontinued for the first few days following vincristine administration, particularly in elderly patients 1

Endocrine Side Effects

• Rare occurrences of syndrome of inappropriate antidiuretic hormone secretion (SIADH) characterized by high urinary sodium excretion with hyponatremia 1
• Hyponatremia can occur, as documented in case reports 7

Pulmonary Side Effects

• Acute shortness of breath and severe bronchospasm have been reported, most frequently when used in combination with mitomycin-C 1
• These reactions may occur minutes to several hours after injection or up to 2 weeks following the dose of mitomycin 1
• Acute respiratory distress syndrome has been reported 1

Hypersensitivity Reactions

• Rare cases of allergic-type reactions, such as anaphylaxis, rash, and edema, temporally related to vincristine therapy have been reported 1

Dermatologic Side Effects

• Alopecia (hair loss) is the most common adverse reaction, though regrowth may occur while maintenance therapy continues 1
• Rash has been reported 1

Other Side Effects

• Fever, headache, dehydration, and hyperuricemia have occurred 1
• Acute uric acid nephropathy may occur after administration, particularly during induction of remission in acute leukemia 1

Risk Factors for Increased Toxicity

• Pre-existing neuropathy significantly increases both incidence and severity of vincristine-induced neuropathy 2
• Advanced age (>65-75 years) is associated with more severe neuropathy 2
• Medical conditions predisposing to neuropathy include diabetes mellitus, renal insufficiency, hypothyroidism, vitamin deficiencies, HIV infection, autoimmune rheumatological conditions, and alcohol abuse 2
• Co-administration with other neurotoxic agents significantly increases neuropathy risk 2
• Concurrent use of CYP3A inhibitors (itraconazole, fluconazole) causes earlier onset and increased severity of neuromuscular side effects 1, 7

Duration and Reversibility

• Most adverse reactions with single weekly doses (leukopenia, neuritic pain, constipation) are usually of short duration (less than 7 days) 1
• Hair loss, sensory loss, paresthesia, difficulty walking, loss of deep-tendon reflexes, and muscle wasting may persist for at least as long as therapy continues 1
• Most neuromuscular symptoms usually disappear by about the sixth week after discontinuance of treatment, though some difficulties may persist for prolonged periods 1
• Median duration of symptoms from discontinuation is 3 months for paresthesias and motor weakness, and 5 months for muscle cramps 3