No

Antineoplastic Agent, Miscellaneous

Palliative treatment of persistent or recurrent ovarian cancer following first-line therapy with a cisplatin- or alkylating agent-based combination

D

Hypersensitivity to altretamine, pre-existing severe bone marrow suppression or severe neurologic toxicity

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Peripheral blood counts and neurologic examinations should be done routinely before and after drug therapy. Use with caution in patients previously treated with other myelosuppressive drugs or with pre-existing neurotoxicity; use with caution in patients with renal or hepatic dysfunction; altretamine may be slightly mutagenic.

>10%:

Central nervous system: Peripheral sensory neuropathy, neurotoxicity

Gastrointestinal: Nausea, vomiting

Hematologic: Anemia, thrombocytopenia, leukopenia

1% to 10%:

Central nervous system: Seizures

Gastrointestinal: Anorexia, diarrhea, stomach cramps

Hepatic: Increased alkaline phosphatase

<1%: Dizziness, depression, rash, alopecia, myelosuppression, hepatotoxicity, tremor

Symptoms of overdose include nausea, vomiting, peripheral neuropathy, severe bone marrow suppression

After decontamination, treatment is supportive

Decreased effect: Phenobarbital may increase metabolism of altretamine

Increased toxicity: May cause severe orthostatic hypotension when administered with MAO inhibitors; cimetidine may decrease metabolism of altretamine

Although altretamine clinical antitumor spectrum resembles that of alkylating agents, the drug has demonstrated activity in alkylator-resistant patients; probably requires hepatic microsomal mixed-function oxidase enzyme activation to become cytotoxic. The drug selectively inhibits the incorporation of radioactive thymidine and uridine into DNA and RNA, inhibiting DNA and RNA synthesis; metabolized to reactive intermediates which covalently bind to microsomal proteins and DNA. These reactive intermediates can spontaneously degrade to demethylated melamines and formaldehyde which are also cytotoxic.

Absorption: Oral: Well absorbed (75% to 89%)

Metabolism: Rapid and extensive demethylation in liver; high concentrations in liver and kidney, but low concentrations in other organs

Half-life: 13 hours

Peak plasma levels: 0.5-3 hours after dose

Elimination: In urine (<1% unchanged)

Adults: Oral (refer to protocol): 4-12 mg/kg/day in 3-4 divided doses for 21-90 days

Alternatively: 260 mg/m²/day for 14-21 days of a 28-day cycle in 4 divided doses

Temporarily discontinue (for greater than or equal to 14 days) & subsequently restart at 200 mg/m²/day if any of the following occurs:

if GI intolerance unresponsive to symptom measures

WBC <2000/mm³

granulocyte count <1000/mm³

platelet count <75,000/mm³

progressive neurotoxicity

Should be administered after meals

Neurotoxicity is common; rarely may produce depression

Bone marrow suppression may be seen; use caution with carbamazepine and clozapine; may produce seizures caution with bupropion and clozapine; may cause severe orthostatic hypotension when administered with MAOIs

No information available to require special precautions

No effects or complications reported

Take as directed, preferably after meals. Avoid alcohol and aspirin or medications containing aspirin. You may experience nausea or vomiting during therapy or several weeks after therapy is discontinued; small frequent meals may help. You will be more susceptible to infection while taking this medication; avoid crowds or persons with infections or contagious conditions. Report any numbness, tingling, or pain in extremities; unrelieved nausea or vomiting; tremors; yellowing of skin or eyes; fever; chills; easy bruising or unusual bleeding; extreme weakness or increased fatigue. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures as recommended by your prescriber. Consult prescriber if breast-feeding.

Advise patient to report any numbness or tingling in extremities to physician; nausea and vomiting may occur and even begin up to weeks after therapy is stopped

Capsule: 50 mg

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Bruckner HW and Schleifer SJ, "Orthostatic Hypotension as a Complication of Hexamethylmelamine Antidepressant Interaction," Cancer Treat Rep, 1983, 67:516.

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Thigpen JT, Vance RB, and Khansur T, "Second-Line Chemotherapy for Recurrent Carcinoma of the Ovary," Cancer, 1993, 71(4 Suppl):1559-64.