Definition
Altretamine, also known by its chemical name hexamethylmelamine, is an antineoplastic alkylating agent used primarily in the treatment of ovarian cancer. It is administered orally and functions as a cytotoxic chemotherapy drug.
Overview
Altretamine was first approved for medical use in the United States in 1990 and has been employed as a component of salvage therapy for patients with persistent or recurrent epithelial ovarian carcinoma, particularly when disease is refractory to platinum‑based regimens. The drug is taken in capsule form, typically in a dose‑escalation schedule that begins with a low daily dose and is increased to a maintenance dose if tolerated.
Pharmacologically, altretamine is believed to exert its anticancer effects through metabolic activation to reactive intermediates that alkylate DNA, leading to cross‑linking and inhibition of DNA synthesis. The exact mechanism of action is not fully elucidated and remains a subject of research.
Common adverse effects include gastrointestinal disturbances (nausea, vomiting, abdominal pain), hematologic toxicity (leukopenia, thrombocytopenia, anemia), fatigue, and alopecia. Rare but serious toxicities such as hepatic dysfunction and secondary malignancies have been reported. Patients are routinely monitored with complete blood counts and liver‑function tests throughout therapy.
Altretamine is contraindicated in patients with severe hepatic impairment and in those who are pregnant or breastfeeding, due to potential fetal harm and excretion in breast milk.
Etymology / Origin
The non‑proprietary name “altretamine” is derived from its chemical structure as a substituted melamine derivative. The prefix “hexamethyl‑” indicates the presence of six methyl groups attached to the melamine core, while the suffix “‑amine” reflects its classification among nitrogen‑containing heterocyclic compounds. The International Nonproprietary Name (INN) was assigned by the World Health Organization to provide a standardized label for the drug across different markets.
Characteristics
| Property | Detail |
|---|---|
| Chemical formula | C₉H₁₂N₆ |
| Molecular weight | 216.24 g·mol⁻¹ |
| Structure | Hexamethylated derivative of melamine; a heterocyclic triazine ring bearing six methyl substituents on its three exocyclic nitrogen atoms. |
| Physical appearance | White to off‑white crystalline powder; sparingly soluble in water, more soluble in organic solvents such as dimethyl sulfoxide. |
| Absorption | Well absorbed after oral administration; peak plasma concentrations occur within 2–4 hours. |
| Distribution | Widely distributed in body tissues; limited plasma protein binding. |
| Metabolism | Hepatically metabolized primarily by oxidative dealkylation; several metabolites have been identified, some of which retain cytotoxic activity. |
| Excretion | Primarily renal; unchanged drug and metabolites are eliminated in urine. |
| Half‑life | Approximately 1.5–2 hours for the parent compound; metabolites may have longer elimination phases. |
| Regulatory status | Approved in the United States, European Union, and several other jurisdictions for ovarian cancer; not available in all countries. |
Related Topics
- Alkylating agents – a broader class of chemotherapy drugs that introduce alkyl groups into DNA, causing cross‑linking and strand breakage.
- Ovarian cancer – malignant neoplasm of the ovary; altretamine is used in recurrent or platinum‑resistant disease.
- Chemotherapy regimens – combination protocols that may include altretamine alongside agents such as paclitaxel, carboplatin, or topotecan.
- Melamine derivatives – chemical family to which altretamine belongs; includes compounds like melamine, which is used industrially, and other pharmacologically active triazines.
- Pharmacovigilance – monitoring for adverse drug reactions, especially important for agents with potential for secondary malignancies.
This entry reflects current, peer‑reviewed pharmacological and clinical information available up to 2024.