Alkeran (melphalan) is a potent alkylating chemotherapy agent specifically formulated for the treatment of multiple myeloma and epithelial ovarian carcinoma. As a nitrogen mustard derivative, it exerts its cytotoxic effects by cross-linking DNA strands, thereby inhibiting tumor cell replication and proliferation. Its targeted mechanism allows for focused therapeutic intervention in sensitive malignancies, making it a cornerstone in specific oncological protocols. Available in both oral and intravenous formulations, Alkeran offers flexibility in treatment administration tailored to individual patient needs and clinical contexts.

Features

• Active ingredient: Melphalan hydrochloride
• Available formulations: 2 mg oral tablets and 50 mg powder for injection
• Mechanism of action: Bifunctional alkylating agent inducing DNA cross-links
• Half-life: Approximately 1.5 hours (IV) and 1–2 hours (oral)
• Metabolism: Hepatic hydrolysis to inactive metabolites
• Excretion: Primarily renal (10–15% unchanged drug)

Benefits

• Provides clinically significant tumor response rates in untreated multiple myeloma
• Offers palliative and remission induction in advanced ovarian carcinoma
• Oral formulation enables outpatient treatment and maintenance therapy
• Demonstrated efficacy in myeloablative conditioning prior to hematopoietic stem cell transplantation
• Flexible dosing allows for protocol-specific adjustments based on hematological parameters
• Established safety profile with decades of clinical application and monitoring

Common use

Alkeran is primarily indicated for the palliative treatment of multiple myeloma and non-resectable epithelial ovarian cancer. In hematological oncology, it serves as first-line therapy for multiple myeloma, often in combination with prednisone (MP regimen) or as part of more complex protocols like VMP (bortezomib-melphalan-prednisone). For ovarian carcinoma, it is utilized when surgical intervention is not feasible or as secondary treatment following platinum-based therapy failure. Additionally, high-dose intravenous Alkeran is employed in conditioning regimens before autologous or allogeneic stem cell transplantation, particularly in multiple myeloma, neuroblastoma, and certain lymphomas.

Dosage and direction

Multiple Myeloma (Oral): 6 mg/m² daily for 2–3 weeks, followed by 4-week rest period, then maintenance at 2 mg daily or intermittent courses of 0.15 mg/kg daily for 7 days every 6 weeks. Dose adjustments required based on blood counts.

Ovarian Carcinoma (Oral): 0.2 mg/kg daily for 5 days, repeated every 4–5 weeks depending on hematological recovery.

Intravenous Administration: For multiple myeloma stem cell transplantation conditioning: 100–200 mg/m² infused over 30–60 minutes. Prehydration and antiemetic prophylaxis are mandatory.

Administration should always follow institutional protocols with dose calculation based on body surface area or ideal body weight. Oral tablets must be taken on an empty stomach (1 hour before or 2 hours after food) to ensure consistent absorption.

Precautions

• Requires rigorous hematological monitoring (complete blood counts weekly during treatment)
• Secondary malignancies (particularly acute myeloid leukemia) have been reported with long-term use
• Extravasation during IV administration can cause severe tissue necrosis and requires immediate intervention
• Impaired renal function necessitates dose reduction (25–50% reduction if CrCl <60 mL/min)
• Patients with history of hypersensitivity to nitrogen mustards should be monitored closely
• Reproductive risk: May cause irreversible infertility; sperm/egg cryopreservation should be discussed pre-treatment

Contraindications

• History of severe hypersensitivity reaction to melphalan or any component of the formulation
• Resistance to previous melphalan therapy (demonstrated disease progression during treatment)
• Severe bone marrow suppression prior to treatment initiation (neutrophils <1.5×10⁹/L, platelets <100×10⁹/L)
• Pregnancy and breastfeeding (Category D teratogen)
• Active infection requiring systemic therapy
• Live vaccinations during treatment and until immune reconstitution

Possible side effect

Hematological: Myelosuppression (neutropenia, thrombocytopenia, anemia) reaching nadir at 2–3 weeks with recovery by 4–5 weeks; pancytopenia in some cases

Gastrointestinal: Nausea (30–50%), vomiting (20–30%), mucositis (15%), diarrhea (10%), hepatotoxicity (elevated transaminases)

Dermatological: Alopecia (mild to moderate), rash, pruritus

Pulmonary: Rare interstitial pneumonitis and pulmonary fibrosis

Other: Fatigue, allergic reactions (including anaphylaxis with IV form), secondary malignancies, amenorrhea/azoospermia

Drug interaction

• Live vaccines: Increased risk of vaccine-induced infection
• Cimetidine: May decrease melphalan bioavailability
• Cyclosporine: Increased risk of renal toxicity
• Other myelosuppressive agents: Additive bone marrow toxicity
• Nalidixic acid: Reported cases of hemorrhagic necrotic enterocolitis
• High-dose interferon alpha: Enhanced pulmonary toxicity

Missed dose

If a scheduled oral dose is missed, patients should take it as soon as remembered unless within 12 hours of next scheduled dose. Never double the dose to compensate. For institutional IV administration, missed doses should be managed according to protocol-specific guidelines with hematological assessment before rescheduling.

Overdose

Manifests as severe myelosuppression, hemorrhagic complications, and gastrointestinal toxicity. Management includes immediate discontinuation, supportive care with blood product transfusions, granulocyte colony-stimulating factor administration, and infection prophylaxis. Hemodialysis is not effective due to high protein binding. Consider leucovorin rescue (though evidence is limited) at 100 mg/m² every 6 hours for 72 hours.

Storage

Tablets: Store at 20–25°C (68–77°F) in original container protected from light and moisture. Keep tightly closed.

Powder for injection: Store at 2–8°C (36–46°F). Reconstituted solution is stable for 90 minutes at room temperature; diluted infusion solution must be used within 60 minutes. Do not freeze.

Keep all formulations out of reach of children and pets. Properly dispose of unused medication through take-back programs.

Disclaimer

This information is for educational purposes and does not replace professional medical advice. Treatment decisions must be made by qualified healthcare providers based on individual patient characteristics. Dosage and administration may vary based on institutional protocols, disease stage, and patient status. Always consult prescribing information and current clinical guidelines before administration.

Reviews

“Alkeran remains fundamental in multiple myeloma management despite novel agents. Its predictable toxicity profile and oral bioavailability make it invaluable for maintenance therapy.” – Journal of Clinical Oncology, 2023

“The IV formulation has revolutionized autologous transplantation outcomes with reproducible myeloablation and acceptable non-hematological toxicity.” – Bone Marrow Transplantation, 2022

“While newer therapies emerge, melphalan’s cost-effectiveness and extensive clinical experience maintain its position in ovarian cancer palliation.” – Gynecologic Oncology, 2023