Melphalan

Indications

Melphalan is used for: Breast cancer, Ovarian cancer, Multiple myeloma, Neuroblastoma, Soft tissue sarcoma, Malignant melanoma, Retinoblastoma, Polycythaemia vera

Adult Dose

Adult Multiple Myeloma Palliative treatment Indicated for the palliative treatment of patients with MM Oral 6 mg PO qDay for 2-3 weeks, OR 10 mg PO qDay for 7-10 days, OR 0.15 mg/kg/day PO for 7 days, THEN After adequate recovery from toxicity (monitor WBCs and platelets) give 1-3 mg or 0.05 mg/kg PO qDay Intravenous If unable to take oral, may administer IV 16 mg/m² IV as a single infusion over 15-20 minutes q2wk for 4 doses, THEN After adequate recovery from toxicity (monitor WBCs and platelets) administer q4wk Conditioning treatment Indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation 100 mg/m²/day IV administered over 30 min for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0) Patients weighing >130% of their ideal body weight, body surface area should be calculated based on adjusted ideal body weight Oral Ovarian Cancer 0.2 mg/kg/day PO for 5 days; repeat q4-5Weeks Breast cancer Adult: 150 mcg/kg daily or 6 mg/m2 daily for 5 days, repeated every 6 wk. Elderly Multiple Myeloma Induction 6 mg PO qDay for 2-3 weeks, OR 10 mg PO qDay for 7-10 days, OR 0.15 mg/kg/day PO for 7 days, OR 16 mg/m² IV q2Weeks for 4 doses Maintenance Wait until WBC and platelet counts rise 1-3 mg PO qDay, OR 0.05 mg/kg/day PO, OR 16 mg/m² IV q4Weeks Ovarian Cancer 0.2 mg/kg/day PO for 5 days; repeat q4-5Weeks

Child Dose

Safety and efficacy not established

Renal Dose

Renal impairment (BUN >30 mg/dL): Consider dosage reduction of up to 50%

Administration

Should be taken on an empty stomach. Take on an empty stomach 1 hr before or 2 hr after meals.

Contra Indications

Hypersensitivity. Severe bone marrow suppression. Pregnancy.

Precautions

Renal impairment. Lactation. Prior bone marrow suppression, prior chemotherapy or irradiation. May mask signs of infection e.g. fever and increased WBC. Elderly. Lactation: not known if excreted in breast milk

Pregnancy-Lactation

Pregnancy Category: D Lactation: not known if excreted in breast milk

Interactions

Potentially Fatal: Fatal haemorrhagic enterocolitis with concurrent nalidixic acid in children. Potentiates risk of renal damage with ciclosporin.

Adverse Effects

Side effects of Melphalan : >10% Myelosuppression (30%) Frequency Not Defined Diarrhoea, stomatitis, vomiting; haemolytic anaemia, vasculitis, pulmonary fibrosis, hepatic disorders, suppression of ovarian function in premenopausal women, temporary or permanent sterility in male patients. Allergic reactions. Potentially Fatal: Bone marrow suppression. Secondary malignancy, cardiac arrest. Anaphylaxis.

Mechanism of Action

Melphalan, a mechlorethamine derivative, is an alkylating antineoplastic agent. It forms carbonium ions, resulting in DNA and RNA synthesis inhibition. It cross-links DNA strands and acts on both resting and rapidly dividing tumour cells.