Paralytic Ileus as a Complication of Chemotherapeutic Agents
Vinca alkaloids (b) are the chemotherapeutic agents most commonly associated with paralytic ileus.
Mechanism and Evidence for Vinca Alkaloids
- Vinca alkaloids (vincristine, vinblastine, vinorelbine) bind to tubulin, prevent microtubule formation, and inhibit mitosis, leading to apoptosis, but also affect the autonomic nervous system causing neurotoxicity 1
- Vincristine specifically causes neuropathy in approximately 27.8% of patients, with constipation (3.5%) and paralytic ileus being recognized adverse effects 1, 2
- Multiple case reports document paralytic ileus as a direct complication of vinca alkaloid administration, particularly vincristine 3, 4, 5
- Vincristine-induced paralytic ileus can occur even at low doses (0.16 mg/m²) in susceptible patients 3
Risk Factors and Mechanisms
- Concomitant use of azole antifungal agents significantly increases the risk of vinca alkaloid-induced neurotoxicity including paralytic ileus by inhibiting CYP3A4, which delays metabolism and excretion of vinca alkaloids 2
- Pre-existing autonomic neuropathy (such as in Parkinson's disease) may predispose patients to vinca alkaloid-induced paralytic ileus 3
- The paralytic ileus results from autonomic neuropathy affecting the myenteric plexus of the intestine 3, 5
Management Considerations
- Prophylactic laxatives, particularly magnesium oxide at doses >2000 mg/day, may help prevent constipation in patients receiving chemotherapy regimens containing vinca alkaloids 6
- Treatment options for established vincristine-induced paralytic ileus include fiberoptic colonoscopy with enema administration and intravenous prostaglandin F2 alpha 4
- Temporary discontinuation of azole antifungal agents during vinca alkaloid treatment may reduce the frequency of severe constipation (p=0.0308) and paralytic ileus (p=0.0967) 2
Other Chemotherapeutic Agents and Gastrointestinal Effects
- Anthracyclines (like doxorubicin) are associated with cardiac arrhythmias but have a lower incidence of gastrointestinal toxicity (15% all-grade diarrhea) 1
- Cyclophosphamide is primarily associated with hemorrhagic cystitis and gonadal toxicity rather than paralytic ileus 1, 7
- Methotrexate is primarily associated with mucositis and hepatotoxicity rather than paralytic ileus 1
- Cisplatin is associated with nausea/vomiting and peripheral neuropathy but has a lower incidence of paralytic ileus compared to vinca alkaloids 1
Clinical Implications
- Patients receiving vinca alkaloids should be monitored for early signs of autonomic neuropathy including constipation 2, 6
- Prophylactic measures should be considered in patients receiving CHOP or CHOP-like regimens (which contain vincristine) to prevent progression to paralytic ileus 6
- Special caution is warranted when administering vinca alkaloids to patients with pre-existing autonomic neuropathy or those concurrently receiving medications that inhibit CYP3A4 2, 3