Overview
Melphalan is a cytotoxic drug belonging to the class of alkylating agents. It is used to treat a range of cancers, most notably multiple myeloma, certain ovarian and breast cancers, and in regional treatments for limb malignancies such as melanoma. Melphalan interferes with DNA integrity and thereby inhibits tumour cell replication. It is administered in several ways depending on the indication, including oral and intravenous routes and specialized regional perfusion techniques.
Mechanism and pharmacology
As an alkylator, melphalan forms covalent bonds with DNA, creating cross-links that block transcription and replication. It is considered cell-cycle nonspecific because it can damage cells at various phases of division. The drug is absorbed when given orally, though bioavailability can vary, and is eliminated primarily via the kidneys. Dose adjustments are often required in impaired renal function and when combined with other myelosuppressive therapies.
Clinical uses
Melphalan has several established roles in oncology. It is a backbone drug in regimens for plasma cell disorders and commonly used as high-dose conditioning before autologous hematopoietic stem cell transplantation for multiple myeloma. For regional control of extremity tumours, isolated limb perfusion with melphalan allows delivery of high local concentrations while limiting systemic exposure. It has been employed in selected ovarian and breast cancer protocols and, in specialised settings, as part of ocular or intra-arterial chemotherapy for certain eye tumours.
Administration and practical considerations
Formulations include oral tablets and parenteral preparations. Treatment plans vary from single high-dose conditioning regimens to repeated lower-dose courses. Because melphalan causes profound bone marrow suppression, scheduling often incorporates growth factor support or stem cell rescue when high doses are used. Clinicians monitor blood counts and renal function closely and counsel patients about fertility risks and preparatory measures when relevant.
Adverse effects and monitoring
Major toxicities stem from its effects on rapidly dividing normal tissues. Common and important adverse reactions include:
- Myelosuppression (neutropenia, thrombocytopenia, anaemia)
- Mucositis and gastrointestinal symptoms
- Risk of infertility and gonadal dysfunction
- Long-term risk of secondary malignancies such as therapy-related leukemia
Regular complete blood counts, renal assessment and long-term follow-up for late effects are standard parts of care.
History and notable distinctions
Melphalan is a derivative of nitrogen mustard compounds developed in the mid-20th century as part of early chemotherapeutic research. It remains distinct among alkylators for its central role in myeloma conditioning regimens and its use in regional perfusion approaches that achieve high local tumour exposure. While alternatives to melphalan exist, the drug is still widely used because of its well-characterised activity and predictable toxicity profile.
For treatment details and evolving indications, clinicians consult oncology guidelines and institutional protocols tailored to tumour type, patient fitness and organ function.