Melphalan
Melphalan is a cytotoxic alkylating agent primarily used in veterinary oncology for the treatment of **multiple myeloma**. It is also utilized as an alternative to cyclophosphamide in canine lymphoma rescue protocols and for the management of certain solid tumors, including ovarian carcinoma, osteosarcoma, and pulmonary or mammary neoplasia. > **Clinical Warning:** Melphalan is a potent cytotoxic drug. Strict safety and handling protocols must be followed to prevent accidental exposure to personnel and owners.
Mecanismo: Melphalan acts as a bifunctional alkylating agent. It forms **inter- and intrastrand cross-links** with DNA → alters DNA structure → **inhibits DNA synthesis and function**, ultimately leading to cell death (apoptosis), particularly in rapidly dividing neoplastic cells.
Vías de administración
Contraindicaciones
- Bone marrow suppression
- Concurrent infection
- Impaired renal function
Efectos adversos
- Myelosuppression (leucopenia, thrombocytopenia)
- Anorexia
- Nausea
- Vomiting
- Pulmonary infiltrates
- Pulmonary fibrosis
- Oral ulceration (reported in humans)
Interacciones farmacológicas
- Cimetidine · Decreases the oral bioavailability of melphalan · moderate
- Steroids · Enhance the antitumour effects of melphalan · moderate
- Ciclosporin · Enhances the risk of renal toxicity (reported in humans) · major
Monitoreo
- Complete Blood Count (CBC) - monitor for leucopenia and thrombocytopenia
- Renal function panel
- Gastrointestinal signs (anorexia, vomiting)
- Respiratory rate and effort (for pulmonary infiltrates/fibrosis)
Sobredosis
Overdosage primarily manifests as severe **myelosuppression** (profound neutropenia and thrombocytopenia) and severe **gastrointestinal toxicity** (vomiting, diarrhea, ulceration). Treatment is supportive, including broad-spectrum antibiotics for neutropenia, antiemetics, and potentially blood transfusions or colony-stimulating factors.
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