Gleostine

Uses

Gleostine is an alkylating drug used for the treatment of patients with:

• Brain tumors, primary and metastatic, following appropriate surgical and/or radiotherapeutic procedures.
• Hodgkin’s lymphoma in combination with other chemotherapies, following disease progression with initial chemotherapy.

Gleostine is also used to associated treatment for these conditions: Primary Brain Tumors, Refractory Hodgkin Lymphoma, Tumors Metastatic to Brain

How Gleostine works

Gleostine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA (at the O6 position of guanine-containing bases) and RNA, thus inducing cytotoxicity. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. As lomustine is a nitrosurea, it may also inhibit several key processes such as carbamoylation and modification of cellular proteins.

Dosage

Gleostine dosage

Adult: 100-130 mg/m2 as a single dose every 6 wk. Adjust dose according to platelet and leukocyte counts. Compromised marrow function: 100 mg/m2 as a single dose every 6 wk.

Child: 75-150 mg/m2 as a single dose every 6 wk. Readjust dose according to platelet and leukocyte counts.

Should be taken on an empty stomach. May be taken at bedtime to reduce occurrence of nausea.

Side Effects

Pulmonary infiltrates, pulmonary fibrosis, nausea, vomiting, hepatotoxicity, nephrotoxicity, stomatitis, alopecia, disorientation, lethargy, dysarthria, ataxia, visual disturbances.

Toxicity

Oral, rat: LD₅₀ = 70 mg/kg. Pulmonary toxicity has been reported at cumulative doses usually greater than 1,100 mg/m2. There is one report of pulmonary toxicity at a cumulative dose of only 600 mg. The onset of toxicity has varied from 6 months after initiation of therapy, to as late as 15 years after.

Precaution

Monitor CBC with differential platelet count wkly for at least 6 wk after a dose. Periodically perform pulmonary function studies and LFTs.

Interaction

Increased levels/ effects with CYP2D6 inhibitors.

Food Interaction

Gleostine Drug Interaction

Unknown: testosterone, bevacizumab, nebivolol, calcium / vitamin d, loratadine, docusate, rosuvastatin, doxycycline, omega-3 polyunsaturated fatty acids, fluticasone, levetiracetam, furosemide, escitalopram, atorvastatin, methadone, multivitamin, omega-3 polyunsaturated fatty acids, cyanocobalamin, ascorbic acid, cholecalciferol

Gleostine Disease Interaction

Major: pulmonary infiltrates/fibrosis, infections, myelosuppressionModerate: renal dysfunctionMinor: hepatic dysfunction

Elimination Route

Well and rapidly absorbed from the gastrointestinal tract.

Half Life

Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours.

Elimination Route

Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours.

Pregnancy & Breastfeeding use

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Pregnancy and lactation.

Special Warning

Renal Impairment:

CrCl <10: Admin 25-50% of normal dose.

CrCl 10-50: Admin 75% of normal dose.

Acute Overdose

Symptoms: Pancytopenia, hepatic dysfunction, abdominal pain, pulmonary toxicity with tachypnoea and hypoxaemia, confusion and disorientation. Severe myelosuppression.

Management: Symptomatic and supportive.

Storage Condition

Store at 15-30° C

Innovators Monograph

You find simplified version here Gleostine