Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
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 | Oral : Rapidly and completely absorbed (in 30-60 minutes) |
Highly lipid soluble, rapid and extensive tissue distribution.
| Cross blood brain barrier? | CSF achieves ≥ 50% of plasma levels |
| PPB |
No information found |
Actively metabolized by hepatic microsomal enzyme oxidation system (P450)
| Active metabolites | Several |
| Inactive metabolites | Yes |
Predominantly renal; < 5% in feces.
| Urine | 75% within 4 days, primarily as metabolites. |
| Half-life |
16-48 hours |
- Brain tumours
- Hodgkin's disease
Other Uses:
- Advanced breast cancer
- Lung cancer (squamous cell, anaplastic large cell, adenocarcinoma)
- Malignant melanoma
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. Patients with FVC or DLCO < 70% of normal are particularly at risk and should be monitored closely.
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of white blood cell count. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxics/radiation therapy. If the patient vomits after 30-45 minutes, do not repeat the dose. 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 % |
Dose reduction required. The following is suggested:
|
Creatinine clearance (mL/min) |
Lomustine (% previous dose) |
|
> 50 |
100 % |
|
10 – 50 |
75 % |
|
< 10 |
50 % |
- Oral self-administration; drug available by outpatient prescription.
- Protect from light.
Lomustine is contraindicated in patients with known hypersensitivity to the drug, and in patients with severe leukopenia and/or thrombocytopenia.
Secondary malignancies, including acute leukemia and bone marrow dysplasias, have been reported following nitrosoureas therapy. Lomustine is carcinogenic, embryotoxic, teratogenic and causes infertility. Lomustine should not be used in pregnancy. Adequate contraception must be used during lomustine treatment and for at least 6 months after treatment cessation. Lomustine metabolites are present in breast milk; therefore, breast feeding is not recommended.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| Cimetidine | Potentiates marrow toxicity of lomustine | Possibly by ↓ metabolism of lomustine | Do not use cimetidine; choose a different H2 blocker |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
| Monitor Type | Monitor Frequency |
|---|---|
| Pulmonary function tests, in at risk patients: extreme caution in patients with FVC or DLCO < 70% |
Baseline |
| CBC | Baseline and regular |
| Liver and renal function tests | Baseline |
| Clinical pulmonary exam, including auscultation, pulmonary toxicity ratings | Periodic |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
| Monitor Type | Monitor Frequency |
|---|---|
| Pulmonary function tests, especially with with prolonged (> 6 months) therapy or cumulative doses > than 1,100 mg/m2 | Baseline and regular |
Cancer Drug Manual (the Manual), 1994, British Columbia Cancer Agency (BCCA)
Product Monograph: CeeNU® (lomustine). Bristol-Myers Squibb Canada, February 20, 2009.
Lomustine: Chemotherapy Drug Manual, Clin-eguide.
June 2019 Updated emetic risk category.
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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