lomustine: clinical use

Prescribing considerations

• Treatment should be supervised by clinicians experienced in cancer chemotherapy.
• Delayed, cumulative myelosuppression is the principal dose-limiting toxicity; previous nadir counts must inform subsequent prescribing decisions.
• Review concomitant marrow-suppressive treatment, organ function, vaccination status and reproductive plans.
• Consider fertility preservation before treatment, particularly as male infertility may be irreversible.
• Long-term nitrosourea exposure has been associated with secondary malignancy risk.

Contraindications and cautions

• Hypersensitivity to lomustine, another nitrosourea or a formulation excipient
• Previous tumour failure to respond to another nitrosourea
• Severe bone-marrow depression
• Severe renal impairment
• Pregnancy or breastfeeding
• Wheat allergy
• Yellow-fever vaccine or another live vaccine in an immunosuppressed patient

Monitoring

• Full blood count before treatment and frequently afterwards because cytopenias are delayed and prolonged
• Baseline and periodic pulmonary-function assessment
• Periodic liver-function and renal-function tests
• Clinical assessment for infection, bleeding, pulmonary toxicity, hepatic injury and renal injury
• Track cumulative exposure because marrow, pulmonary and renal toxicity may be cumulative

Clinical pharmacology

Lomustine is an orally absorbed, lipophilic nitrosourea alkylating agent. Reactive metabolites damage DNA and interfere with nucleic-acid synthesis and repair; metabolites cross the blood–brain barrier and are eliminated mainly through the kidneys.

Formulation and product differences

• The selected product is a blue hard capsule containing lactose and wheat starch.
• Its very low gluten content is considered unlikely to affect people with coeliac disease, but it is contraindicated in wheat allergy.
• Capsules must remain intact and be swallowed whole; damaged capsules create a cytotoxic-exposure risk.