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Lomustine (Gleostine) - Uses, Dose, Side effects, MOA, Brands

Lomustine (also known by its brand name, CeeNU among others) is an alkylating antineoplastic agent. This means it works by damaging the DNA of cancer cells, which stops them from growing and dividing. It's used primarily in the treatment of certain types of brain tumors, Hodgkin's lymphoma, and non-Hodgkin's lymphoma.

Lomustine (Gleostine) is an alkylating agent that is used in combination with other chemotherapeutic drugs to treat certain malignant conditions such as brain tumors and Hodgkin's lymphoma.

Lomustine Uses:

Brain tumors:
- It is used in the treatment of primary and metastatic brain tumors after appropriate surgery, radiotherapy, or chemotherapy if indicated.
Hodgkin lymphoma:
- It is used in treatment in combination with other chemotherapeutic agents of Hodgkin lymphoma which has relapsed or progressed following initial chemotherapy.
- But, the use of lomustine in the management of Hodgkin lymphoma is limited due to the efficacy of other chemotherapy agents/regimens.

Lomustine Dose in Adults:

Note:

Only give enough lomustine capsules for one dose at a time.
Don't give another dose until the person has enough white blood cells and platelets in their blood.
The dose amount should be rounded to the closest 10 mg.
Lomustine can make someone feel like throwing up, so it's a good idea to give medicine to prevent this.

Lomustine Dose in the treatment of Brain tumors:

For brain tumors, take 130 mg/m of lomustine once every 6 weeks.
But, if the patient has weaker bone marrow, reduce it to 100 mg/m once every 6 weeks.
If using with other cancer drugs, the dose might be adjusted.

Lomustine Dose in the treatment of Anaplastic oligodendroglioma:

For Anaplastic oligodendroglioma, using the PCV method, take 130 mg/m of lomustine once every 6 weeks, for up to 4 times before starting radiation.
This is combined with two other drugs, procarbazine and vincristine.

Lomustine Dose in the treatment of high-grade Astrocytoma:

For high-grade Astrocytoma in adults aged 21 and under: Using the POC method, take 100 mg/m of lomustine once every 6 weeks, for a total of 8 times.
This is used with two other medicines, vincristine and prednisone.

Lomustine Dose in the treatment of Recurrent Glioblastoma:

For treating returning Glioblastoma:

Using the PCV method: Take 110 mg/m of lomustine once every 6 weeks, for 7 times, along with procarbazine and vincristine.
Using only lomustine: Take between 100 to 130 mg/m once every 6 weeks, and continue until the disease gets worse or the side effects are too strong.

Lomustine Dose in the treatment of Medulloblastoma (off-label dosing):

For treating Medulloblastoma in adults aged 21 and under:

Take 75 mg/m of lomustine once every 6 weeks, for a total of 8 times.
This is combined with two other drugs, cisplatin and vincristine.

Lomustine Dose in the treatment of Hodgkin lymphoma:

For treating Hodgkin lymphoma:

Take 130 mg/m of lomustine once every 6 weeks.
If the patient's bone marrow isn't working well, lower the dose to 100 mg/m once every 6 weeks.
The dose might be adjusted if used with other cancer drugs.

Important: Lomustine isn't used much for Hodgkin lymphoma because other cancer drugs work better.

Lomustine Dose in Childrens:

Important:

Lomustine should only be taken once every 6 weeks. Don't take it daily; that can be dangerous.
Wait to take the next dose until the blood has enough white cells (more than 4,000/mm) and platelets (more than 100,000/mm).
If lomustine is taken with other medicines, the dose and timing might change. Always check the specific plan.

Lomustine Dose in the treatment of Brain tumors:

General Instructions:

For Infants, Children, and Teens: Take 130 mg/m of lomustine once every 6 weeks. If used with other cancer drugs, the amount might change.

If Bone Marrow is Weak:

Start with a lower dose: 100 mg/m once every 6 weeks. Future doses might change depending on blood cell counts.

Medulloblastoma:

For Children 3 and older: Not much data, but some suggest taking 75 mg/m at the start of each treatment cycle. This is combined with cisplatin, vincristine, and radiation.

Gliomas:

Low-grade: For infants, children, and teens: 110 mg/m on the 3rd day of a 6-week cycle, combined with other drugs. This is suggested for up to 8 cycles for certain gliomas.
High-grade:
- Astrocytoma & Glioblastoma (Jakacki 2016): For children 3 and older: 90 mg/m once every 42 days (or when blood counts are okay), combined with temozolomide and after radiation. This is suggested for 6 cycles.
- POC method for Astrocytoma: For children 18 months and older: 100 mg/m once every 6 weeks for 8 cycles. This is used with vincristine and prednisone.

Lomustine Dose in the treatment of Hodgkin lymphoma:

For Infants, Children, and Teens:

Start with 130 mg/m of lomustine taken by mouth once every 6 weeks. If combined with other cancer medicines, the dose might need to change.
Future doses might change depending on blood cell counts.

If Bone Marrow is Weak:

Begin with a lower dose: 100 mg/m once every 6 weeks.

Lomustine Dosage adjustment based on toxicity:

Dosage adjustments in infants, children, and teens based on side effects:

Blood Cell Counts (lowest levels for next treatments):

Good Levels:
- White blood cells: 3,000/mm or more
- Platelets: 75,000/mm or more
- Dose: No change needed.
Medium Levels:
- White blood cells: 2,000 to 2,999/mm
- Platelets: 25,000 to 74,999/mm
- Dose: Take 70% of the last dose.
Low Levels:
- White blood cells: less than 2,000/mm
- Platelets: less than 25,000/mm
- Dose: Take 50% of the last dose.

Other Side Effects:

If there's lung damage (pulmonary fibrosis): Stop taking the medicine forever.

Lomustine Pregnancy Category: D

Lomustine might harm unborn babies, according to how it works and tests on animals. So:

Women who can become pregnant should use strong birth control while on lomustine and for 2 weeks after their last dose.
Men with partners who can become pregnant should use birth control while on lomustine and for 3.5 months after their last dose.

Use of lomustine while breastfeeding

We don't know if lomustine passes into breast milk.
But to be safe, women shouldn't breast-feed while taking it and for 2 weeks after their last dose.

Lomustine Dose in Kidney Disease:

The manufacturer doesn't give special dose instructions. But some experts suggest:

Based on Aronoff 2007:

If kidney function (CrCl) is between 10-50 mL/minute: Take 75% of the usual dose.
If CrCl is below 10 mL/minute: Take between 25% and 50% of the usual dose.
If on CAPD (a type of dialysis): Take between 25% and 50% of the usual dose.

Based on Kintzel 1995:

If CrCl is 46-60 mL/minute: Take 75% of the usual dose.
If CrCl is 31-45 mL/minute: Take 70% of the usual dose.
If CrCl is 30 mL/minute or less: Don't use lomustine.
If on hemodialysis: Lomustine doesn't get removed because it likes fat (lipophilic). So, no extra dose is needed after dialysis.

Dose in Liver disease:

The maker of lomustine doesn't give special dose instructions for liver problems.
But since the liver processes lomustine, be careful when giving it to someone with liver issues.

Common Side Effects of Lomustine:

Gastrointestinal:
- Nausea and vomiting
Hematologic & oncologic:
- Leukopenia
- Bone marrow depression
- Thrombocytopenia

Less common Side effects of Lomustine:

Central Nervous System:
- Ataxia
- Disorientation
- Dysarthria
- Lethargy
Dermatologic:
- Alopecia
Gastrointestinal:
- Stomatitis
Genitourinary:
- Azotemia (Progressive)
- Nephron Atrophy
- Nephrotoxicity
Hematologic & Oncologic:
- Acute Leukemia
- Anemia
- Bone Marrow Dysplasia
Hepatic:
- Hepatotoxicity
- Increased Serum Alkaline Phosphatase
- Increased Serum Bilirubin
- Increased Serum Transaminases
Ophthalmic:
- Blindness
- Optic Atrophy
- Visual Disturbance
Renal:
- Renal Failure
Respiratory:
- Pulmonary Fibrosis
- Pulmonary Infiltrates

Contraindications to Lomustine:

In the US:

The manufacturer doesn't list any reasons not to use lomustine.

In Canada:

Don't use lomustine if you're allergic to it or any part of it, or if you have very low white blood cell or platelet counts.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

Serious Warning in the US:
- Lomustine can harm the bone marrow and lead to severe blood problems, including fatal ones.
- This effect gets worse with higher doses and accumulates over time.
- It usually shows up 4 to 6 weeks after taking the medicine and lasts about 1 to 2 weeks.
- Platelet problems are often worse than white blood cell problems.
- The bone marrow issues from lomustine are more severe and last longer.
- Doctors need to watch blood counts for at least 6 weeks after each dose.
- Don't take lomustine more often than every 6 weeks.
- Changes in dose should depend on how low the blood counts went after the previous dose.

In Canada:
- People with severe low white blood cell or platelet counts shouldn't use lomustine.

Gastrointestinal toxicities:

Lomustine can moderately cause nausea and vomiting.
It's a good idea to take medicines to prevent this.
Some people also get mouth sores from it.

Hepatotoxicity

Lomustine can harm the liver and raise certain liver test results.
Keep an eye on liver health when using it.

Toxicity in the lungs:

Lomustine can harm the lungs, leading to lung issues like fibrosis.
This is more likely when total doses go over 1,100 mg/m.
The damage might not show up until 6 months or longer after starting the medicine.
People with initial lung problems or who are young might be more at risk.
Test lung function before starting and often during treatment.
If someone gets pulmonary fibrosis from it, they should stop taking lomustine forever.

Toxicity in the renal system:

Lomustine can damage the kidneys, even causing them to shrink.
Be extra careful when giving it to people with kidney problems.
They might need a different dose.
Keep an eye on kidney function when using it.

Secondary malignancies

Using nitrosoureas like lomustine for a long time can lead to other cancers, including a type of blood cancer and bone marrow disorders.

Lomustine: Drug Interaction

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live).
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lenograstim	Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Palifermin	May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
Upadacitinib	Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live).