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.
Side 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.
Mode 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.