Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
lomustine
Lomustine is a highly lipophilic nitrosourea compound, which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA. Other biologic effects include inhibition of DNA and RNA synthesis. Nitrosoureas generally lack cross-resistance with other alkylating agents; however, cross-resistance between lomustine and carmustine has been described.
| Bioavailability |
Rapidly and completely absorbed (in 30-60 minutes) |
Highly lipid soluble, rapid and extensive tissue distribution.
| Cross blood brain barrier? |
Yes (CSF achieves ≥ 50% of plasma levels) |
| PPB |
No information found |
Actively metabolized by hepatic microsomal enzyme oxidation system (P450)
| Active metabolites |
Yes |
| Inactive metabolites | Yes |
Predominantly renal; < 5% in feces.
| Urine |
~50% within 24 hours (metabolites) |
| Half-life |
16-48 hours (metabolites) |
- Brain tumours
- Hodgkin's lymphoma
Refer to the product monograph for a full list and details of approved indications
Emetogenic Potential:
Extravasation Potential: Not applicable
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Dermatological | Alopecia (rare) | E | |||
| Gastrointestinal | Mucositis (rare) | E | |||
| Nausea (or vomiting - 45-100%) | I | ||||
| Vomiting | I | ||||
| General | Fatigue | E | |||
| Hematological | Myelosuppression (65%) | D | |||
| Hepatobiliary | ↑ LFTs (transient, unusual) | E | |||
| Neoplastic | Leukemia (secondary) | L | |||
| MDS | L | ||||
| Nervous System | Ataxia (rare) | E | |||
| Confusion (disorientation - rare) | E | ||||
| Dysarthria (rare) | E | ||||
| Ophthalmic | Blurred vision (blindness - rare) | E | |||
| Optic nerve disorder (optic atrophy - rare) | E | ||||
| Renal | Nephrotoxicity | L | |||
| Reproductive and breast disorders | Infertility | L | |||
| Respiratory | Lung infiltrate (rare, dose-related) | D | |||
| Pulmonary fibrosis (rare, dose-related) | D | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
Myelosuppression is the principal dose limiting toxicity, may be delayed in onset (4-6 weeks) and is cumulative.
Nausea and vomiting is very common. Nausea may be minimized by giving the dose on an empty stomach; antiemetics should be used prophylactically.
Pulmonary toxicity with infiltrates and pulmonary fibrosis have been reported at cumulative doses usually greater than 1,100 mg/m2. The onset of toxicity has varied from 6 months after initiation of therapy, to as late as 15 years after.
Refer to protocol by which the patient is being treated.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Dose should be calculated to the nearest 10 mg to accommodate capsule sizes.
Oral: 130 mg/m² Every 6 weeks
Oral: 100 mg/m² Every 6 weeks
Dosage with myelosuppression:
- Do not retreat until leukocytes > 4 x 109/L and platelets > 100 x 109/L.
- Reduce next dose according to nadir counts as follows:
|
Nadir after prior dose |
|
|
|
Leukocytes (x 109/L) |
Platelets (x 109/L) |
Lomustine (% previous dose) |
|
≥ 4 |
≥ 100 |
100 % |
|
3 – <4 |
75 – <100 |
100 % |
|
2 – <3 |
25 – <75 |
70 % |
|
<2 |
< 25 |
50 % |
The following dose is suggested for renal impairment (Aronoff et al):
|
Creatinine clearance (mL/min) |
Lomustine (% previous dose) |
|
> 50 |
100 % |
|
10 – 50 |
75 % |
|
< 10 |
50 % |
Other references suggested to discontinue lomustine for creatinine clearance < 30mL/min (Krens et al 2019, Kintzel et al 1995).
-
Lomustine capsules should be swallowed whole with a glass of water, and not crushed, dissolved, or opened.
-
Administer lomustine on an empty stomach to prevent nausea and vomiting.
-
If the patient vomits after 30-45 minutes, do not repeat the dose. Studies indicated that the nausea and vomiting occur after drug absorption has taken place.
-
Store at room temperature. Protect from light. Avoid excessive heat (over 40°C).
- Patients who are hypersensitive to this drug or any of its components
- Patients with severe leukopenia and/or thrombocytopenia
- Use extreme caution in patients with FVC or DLCO < 70% of normal due to increased risk for pulmonary toxicity; monitor patients closely.
- Use of live vaccines is not recommended in immunosuppressed patients, including patients treated with lomustine, due to increased risk of fatal systemic vaccine disease.
Other Drug Properties:
-
Carcinogenicity:
Yes
Secondary malignancies, including acute leukemia and bone marrow dysplasias, have been reported following nitrosoureas therapy.
-
Embryotoxicity:
Yes
-
Mutagenicity:
Yes
-
Teratogenicity:
Yes
-
Pregnancy:
Lomustine is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners during treatment, and for at least 6 months after the last dose.
-
Excretion into breast milk:
Likely
Breastfeeding is not recommended during treatment.
-
Fertility effects:
Probable
Documented in animal studies with male animals. Consider sperm preservation prior to treatment.
No drug interaction studies have been performed. Animal studies suggest that CYP2C19, CYP2D6 and CYP3A4 are involved in lomustine metabolism.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Cimetidine | Potentiates marrow toxicity of lomustine | Possibly by ↓ metabolism of lomustine | Do not use cimetidine; choose a different H2 blocker |
| Enzyme-inducing antiepileptic drugs (e.g. carbamazepine, phenytoin) | May affect antiepileptic and lomustine efficacy | Possible ↑ in drug metabolism due to enzyme induction | Avoid concurrent use. If unavoidable, monitor both drugs for reduced efficacy. |
| Enzyme inhibitors drugs (e.g., valproic acid) | May ↑ lomustine toxicity | Possible ↓ in drug metabolism due to enzyme inhibition | Caution. |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
| Monitor Type | Monitor Frequency |
|---|---|
CBC |
Baseline, before each cycle, and as clinically indicated (more frequently after initiation) |
Liver and renal function tests |
Baseline and before each cycle |
Pulmonary function test and pulmonary exam |
Baseline and as clinically indicated |
Clinical toxicity assessment for infection, bleeding, lung and GI effects |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Aronoff, G. R (2007). Drug prescribing in renal failure : dosing guidelines for adults (5th ed.). American College of Physicians
BC Cancer Protocol Summary for Lomustine (CCNU) for Treatment of Recurrent Malignant Brain Tumours. 1 Feb 2022.
eviQ Cancer Treatments Online. Glioblastoma recurrent lomustine. Cancer Institute NSW. 24 February 2023. V1.
Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev 1995;21(1):33-64.
Krens S D, Lassche, Jansman G F G A, et al. Dose recommendations for anticancer drugs in patients with renal or hepatic impairment. Lancet Oncol 2019; 20: e201–08..
Lomustine: Cancer Drug Manual , British Columbia Cancer Agency (BCCA) Drug Manual, Jun 5, 2018.
Lomustine: Chemotherapy Drug Manual, Clin-eguide.
Prescribing Information: Gleostine® (lomustine). NextSource Biotechnology, LLC. September 2018.
Product Information: CeeNU® (lomustine). Bristol-Myers Squibb Australia Pty Ltd. 22 May 2024.
Product Monograph: CeeNU® (lomustine). Bristol-Myers Squibb Canada, February 20, 2009 and February 17, 2016.
Summary of Product Characteristics: Lomustine “medac” 40 mg. medac, 04/2024.
August 2024 Updated Pharmacokinetics, Indications, Dosing, Administration Guidelines, Special Precautions, Interactions and Monitoring sections
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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