Alkeran (melphalan) is a potent alkylating chemotherapeutic agent indicated for the palliative treatment of multiple myeloma and non-resectable epithelial ovarian carcinoma. As a nitrogen mustard derivative, it exerts its cytotoxic effects by cross-linking DNA strands, thereby inhibiting cellular replication and inducing apoptosis in rapidly dividing malignant cells. Its selective activity against hematopoietic and lymphoid tissues makes it particularly valuable in hematologic oncology and certain solid tumor protocols. Available in both oral and intravenous formulations, Alkeran represents a cornerstone therapy with decades of clinical validation supporting its efficacy and safety profile when administered under appropriate medical supervision.

Features

• Active ingredient: Melphalan hydrochloride
• Available formulations: 2 mg oral tablets; 50 mg intravenous powder for reconstitution
• Mechanism: Bifunctional alkylating agent forming DNA interstrand cross-links
• Half-life: Approximately 1.5 hours (IV); 60-90 minutes (oral)
• Metabolism: Hydrolysis in plasma; minimal hepatic involvement
• Excretion: Primarily renal (10-15% unchanged drug)
• Storage: Tablets – room temperature; IV formulation – refrigerated
• Pregnancy category: D (positive evidence of human fetal risk)

Benefits

• Demonstrated efficacy in reducing tumor burden in treatment-naïve and relapsed multiple myeloma
• Provides palliative response and extended progression-free survival in advanced ovarian carcinoma
• Oral formulation enables outpatient treatment and maintenance therapy
• Established dosing protocols with predictable toxicity management
• Cost-effective compared to newer biologic therapies
• Synergistic activity with prednisone, bortezomib, and other antineoplastic agents

Common use

Alkeran is primarily employed as first-line therapy for multiple myeloma, typically in combination with prednisone (MP regimen) or as part of more complex protocols like MPT (melphalan, prednisone, thalidomide) or VMP (bortezomib, melphalan, prednisone). In ovarian cancer, it is reserved for palliation in cases where surgical intervention is not feasible and platinum-based therapies have failed. Off-label uses include conditioning regimens for hematopoietic stem cell transplantation, particularly in amyloidosis and certain lymphoproliferative disorders. Treatment cycles are generally administered every 4-6 weeks to allow hematopoietic recovery.

Dosage and direction

Multiple myeloma (oral): 0.15 mg/kg/day for 7 days every 4-6 weeks, combined with prednisone. Alternatively, 0.25 mg/kg/day for 4 days repeated every 4-6 weeks. Ovarian carcinoma (oral): 0.2 mg/kg/day for 5 days repeated every 4-5 weeks. IV administration: 16 mg/m² administered at 2-week intervals for 4 doses, then at 4-week intervals following hematologic recovery. Dosage must be adjusted based on blood counts prior to each cycle – typically withhold if leukocytes <3000/μL or platelets <100,000/μL. Tablets should be taken on an empty stomach as food reduces bioavailability.

Precautions

Complete blood counts must be monitored weekly during treatment and for at least 3 weeks post-therapy. Use with extreme caution in patients with recent radiation or chemotherapy due to cumulative myelosuppression. Secondary malignancies including acute nonlymphocytic leukemia have been reported with long-term use. Pulmonary fibrosis and interstitial pneumonitis may occur, particularly with prolonged administration. Perform renal function assessment before initiation – dose reduction required in renal impairment. Handle tablets with gloves to prevent accidental exposure; never crush or break tablets due to cytotoxic risk.

Contraindications

Hypersensitivity to melphalan or any component of the formulation. Resistance to previous melphalan therapy. Pregnancy and breastfeeding. Absolute neutrophil count <1500/μL or platelet count <75,000/μL at initiation. Concurrent live vaccination. Active infection requiring systemic therapy. Severe renal impairment (CrCl <30 mL/min) without dose adjustment.

Possible side effect

Hematologic: Myelosuppression (neutropenia, thrombocytopenia, anemia) reaching nadir at 2-3 weeks with recovery by 4-5 weeks. Gastrointestinal: Nausea (30-50%), vomiting (20-30%), stomatitis, diarrhea. Dermatologic: Alopecia (rare), rash, pruritus. Pulmonary: Fibrosis, pneumonitis with chronic use. Reproductive: Amenorrhea, azoospermia, infertility. Other: Allergic reactions including anaphylaxis (more common with IV), hepatotoxicity, secondary malignancies.

Drug interaction

Live vaccines: Increased risk of vaccine-induced infection. Nephrotoxic drugs (aminoglycosides, NSAIDs): Enhanced renal toxicity. Cimetidine: Decreased melphalan bioavailability. Cyclosporine: Increased risk of renal impairment. Other myelosuppressive agents: Additive bone marrow suppression. Suzukacillin: May inhibit antitumor activity. High-dose interferon alpha: Increased pulmonary toxicity.

Missed dose

If a dose is missed, administer as soon as remembered unless within 12 hours of next scheduled dose. Never double doses to make up for missed administration. Contact treating oncologist for guidance on regimen adjustment. Maintain strict adherence to scheduled cycles to ensure optimal therapeutic levels.

Overdose

Manifests as severe myelosuppression with pancytopenia, hemorrhagic complications, and opportunistic infections. Management includes hospitalization with supportive care: transfusion support, granulocyte colony-stimulating factors, broad-spectrum antibiotics, and reverse isolation. Hemodialysis is not effective due to high protein binding. Consider leukapheresis in extreme cases. Monitor hematologic parameters daily until recovery.

Storage

Tablets: Store at 20-25°C (68-77°F) in original container protected from light and moisture. Keep tightly closed. IV powder: Refrigerate at 2-8°C (36-46°F). Reconstituted solution stable for 90 minutes at room temperature; diluted solution stable for 60 minutes. Dispose according to cytotoxic drug guidelines. Keep out of reach of children and pets.

Disclaimer

This information describes uses, dosages, and precautions but does not cover all possible indications, interactions, or adverse effects. Treatment decisions must be made by qualified oncology specialists based on individual patient characteristics. Dosage may require modification based on hematologic parameters, renal function, and treatment response. Regular monitoring is essential throughout therapy.

Reviews

Clinical studies demonstrate overall response rates of 50-60% in multiple myeloma with MP regimen, with median duration of response of 18-24 months. In ovarian cancer, response rates of 30-40% have been observed in platinum-resistant cases. Long-term follow-up shows consistent hematologic toxicity manageable with dose adjustments. The oral formulation is generally well-tolerated with appropriate antiemetic prophylaxis. Older patients may require more aggressive supportive care due to reduced bone marrow reserve.