Lomustine

A to Z Drug Facts

Actions Its mechanism of action involves the inhibition of both DNA and RNA synthesis through DNA alkylation. Lomustine has been shown to affect a number of cellular processes including RNA, protein synthesis, and the processing of ribosomal and nucleoplasmic messenger RNA; DNA base component structure; the rate of DNA synthesis and DNA polymerase activity. It is cell cycle non-specific. The lipid soluble nitrosoureas are rapidly and completely absorbed when given orally; appearance in plasma occurs » 10 min postadministration and peak levels of metabolites appear in » 3 hr. The lipid solubility of lomustine results in extensive tissue distribution. Blood-brain penetration is good; cerebrospinal fluid levels of 15% to 50% of those in plasma have been noted. Lomustine is rapidly degraded, apparently in the liver, to several cytotoxic metabolites. Ther serum half-life of the metabolites ranges from 16 hr to 2 days. About 50% of the dose is excreted in the form of degradation products within 24 hr. Small amounts are excreted via the feces and lungs.

 Indications

Adult

Brain tumors, Hodgkin disease.

Pediatric

Brain tumors, Hodgkin disease.

 Contraindications Standard considerations.

 Route/Dosage

Brain Tumors, Hodgkin Disease

ADULTS: PO 100 to 130 mg/m² administered as a single dose q 6 wk. Do not administer repeat doses of lomustine until leukocyte and platelet counts have recovered to acceptable levels (usually 4000/mm³ and 100,000/mm³, respectively). Reduce lomustine dose if administered with other myelosuppressive drugs. Give 100 mg/m² to patients with compromised bone marrow function. Some clinicians advocate dosage reductions of 25% when platelet nadirs are 50,000 to 74,999/mm³, 50% when platelet nadirs are 25,000 to 49,999/mm³, and 75% when platelet nadirs are < 25,000/mm³.

PEDIATRIC: PO 75 to 150 mg/m² administered as a single dose q 6 wk. Do not administer repeat doses of lomustine until leukocyte and platelet counts have recovered to acceptable levels (usually 4000/mm³ and 100,000/mm³, respectively). Follow dosage adjustment guildelines recommended for adults.

Suggested Lomustine Dose Following Initial Dose

ADULTS: PO Give 100% of the prior dose if the leukocytes > 3000 cells/mm³ and the platelets > 75,000 cells/mm³. Give 70% of the prior dose if the leukocytes are 2000 to 2999 cells/mm³ and the platelets are 25,000 to 74,999 cells/mm³. Give 50% of the prior dose if the leukocytes are < 2000 cells/mm³ and the platelets < 25,000 cells/mm.

Interactions

Alcohol

Lomustine is soluble in alcohol. Some sources recommend avoidance of alcohol on days that lomustine is administered to avoid possible effects on the absorption of lomustine, although there is no documentation of an interaction.

Lab Test Interferences None well documented.

 Adverse Reactions

CNS: Disorientation; lethargy; ataxia; slurred speech. GI: Very high potential for nausea and vomiting with doses ³ 60 mg/m², moderate to high potential for nausea and vomiting with doses < 60 mg/m²; anorexia; transient elevation of LFTs. HEMATOLOGIC: Bone marrow suppression, nadir at 4 to 6 wk. RENAL: Renal failure associated with large cumulative dose. OTHER: Acute leukemia and myelodysplastic disorders have occurred after long-term nitrosourea therapy.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: See Administration and Dosage. Hematologic: The most frequent and most serious toxicity is delayed myelosuppression. It usually occurs 4 to 6 wk after drug administration and is dose-related. Thrombocytopenia occurs » 4 wk after a dose. Leukopenia occurs » 5 to 6 wk after a dose and persists for 1 to 2 wk. About 65% of patients develop WBC counts < 5000/mm³, and 36% of patients develop WBC counts < 3000/mm³. Thrombocytopenia is generally more severe than leukopenia. Anemia also occurs, but is less frequent. Hepatic toxicity: A reversible type of hepatic toxicity, manifested by increased transaminase, alkaline phosphatase, and bilirubin levels, has occurred in a small percentage of patients. Renal toxicity: Decrease in kidney size, progressive azotemia, and renal failure have occurred in patients who received large cumulative doses after prolonged therapy. Pulmonary toxicity: Pulmonary toxicity characterized by pulmonary infiltrates or fibrosis occurs rarely and appears to be dose-related. Onset of toxicity has occurred after an interval of ³ 6 mo from start of therapy with cumulative doses usually > 1100 mg/m². Fertility impairment: There have been reports of persistent testicular damage causing infertility. Secondary malignancies: Long-term use of nitrosoureas may be associated with development of secondary malignancies.

 Administration/Storage

• Store in well-closed containers at room temperature. Lomustine capsules are stable for ³ 2 yr when stored properly. Avoid excessive heat (> 40°C).
• Adminster orally. Take lomustine on an empty stomach; avoid alcohol on that day.
• Follow procedures for proper handling and disposal of anticancer drugs. Wear gloves and avoid skin exposure and inhalation of fumes.

 Assessment/Interventions

• Major toxicity is delayed bone marrow suppression; monitor blood counts weekly for 6 wk after a dose. Monitor liver and renal function periodically.
• Conduct baseline pulmonary function studies during treatment. Patients with a baseline < 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DL_CO) are particularly at risk.
• Nausea and vomiting may occur 3 to 6 hr after an oral dose and usually lasts < 24 hr. Antiemetics prior to dosing may diminish and sometimes prevent these effects. May also be reduced by administration to fasting patients.

 Patient/Family Education

• Notify physician if fever, chills, sore throat, unusual bleeding or bruising, shortness of breath, dry cough, swelling of feet or lower legs, yellowing of eyes and skin, confusion, sores on the mouth or lips, or unusual tiredness occurs.
• Medication may cause loss of appetite; nausea; vomiting; hair loss; skin rash or itching (infrequent); notify health care provider if these reactions become pronounced.
• Take on an empty stomach to reduce nausea.
• Avoid alcohol for short periods after taking a dose of lomustine.
• Contraceptive measures are recommended during therapy.

Books@Ovid
Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts