Melphalan


Melphalan or L-PAM (Alkeran™) is a bifunctional alkylating agent. By its two alkyl groups, it covalently binds with nucleophile groups of both DNA strands. It then disturbs the separation and the replication of DNA.

 

Formula of melphalan

Main indications

The indications are very restricted

mainly to multiple myeloma, for which it was previously the major indication, however new treatments are emerging for myeloma,

ovarian carcinoma or breast adenocarcinoma, for which there is no other active treatment available.

Dosage

In myeloma, the usual oral dose is 3 x 2 mg tablets per day. Every week, the dose is adjusted as required according to blood count results. After 3 to 4 weeks, a maintenance dose of 2 mg may be instituted.

There are great absorption variations: for this reason, many authors recommend the absorption of tablets before eating, since simultaneous feeding can vary the area under curve by at least 40%. The drug’s plasmatic half-life is 90 minutes.

Main toxicities

Only specific toxicities (or major toxicities) are described here. Other common chemotherapy toxicities are described in the chapter on chemotherapy toxicity.

Chemo-induced leukaemia

This risk is relatively high for ovarian cancers or myeloma which respond to this chemotherapy. Chemo-induced leukaemia is very resistant to any new therapy. It generally occurs before 5 years.

Bone marrow insufficiency

After prolonged use, noticeably in older people.

Pulmonary fibrosis

Rare and delayed effect.

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