What is the dosage and usage of Melphalan (multiple myeloma treatment) versus Flutamide (prostate cancer treatment)?

Melphalan vs. Flutamide: Dosage and Usage Guidelines

For multiple myeloma, melphalan is typically administered at 0.25 mg/kg/day orally for 4 days with prednisone 2 mg/kg/day for 4 days, repeated every 4-6 weeks, while flutamide is not indicated for multiple myeloma but rather for prostate cancer at a standard dose of 250 mg orally every 8 hours. 1, 2

Melphalan Dosing for Multiple Myeloma

Oral Melphalan Regimens

• Standard regimen (elderly/transplant-ineligible patients):
  • Melphalan 0.25 mg/kg/day orally for 4 days (0.20 mg/kg/day for patients >75 years)
  • Prednisone 2 mg/kg/day orally for 4 days
  • Repeated every 4-6 weeks until stable response is achieved 1

Intravenous Melphalan Regimens

• Standard IV dose: 16 mg/m² every 2 weeks for 4 doses, then every 4 weeks after adequate recovery 2
• High-dose therapy (transplant-eligible patients): 200 mg/m² as preparative regimen before autologous stem cell transplantation 1
• Reduced-intensity for elderly: 100-140 mg/m² for patients 65-75 years 1

Combination Regimens with Melphalan

1. VMP (Bortezomib-Melphalan-Prednisone):

   • Melphalan 9 mg/m² orally days 1-4
   • Prednisone 60 mg/m² orally days 1-4
   • Bortezomib 1.3 mg/m² subcutaneously days 1,8,15,22
   • Repeated every 35 days 1

2. MPT (Melphalan-Prednisone-Thalidomide):

   • Melphalan 0.25 mg/kg orally days 1-4
   • Prednisone 2 mg/kg orally days 1-4
   • Thalidomide 100-200 mg orally days 1-28
   • Repeated every 6 weeks 1

Dose Adjustments for Melphalan

• Renal impairment:

  • BUN ≥30 mg/dL: Reduce dose by 50% 2
  • GFR <40 mL/min: Reduce dose to 50% 1
  • GFR <30 mL/min: Avoid oral melphalan unless patient is on hemodialysis 1

• Based on blood counts:

  WBC/mm³	Platelets	Percent of Full Dose
  ≥4,000	≥100,000	100%
  ≥3,000	≥75,000	75%
  ≥2,000	≥50,000	50%
  <2,000	<50,000	0%
  2

Melphalan Flufenamide (Melflufen)

Melflufen is a newer peptide-drug conjugate form of melphalan that shows promise in relapsed/refractory multiple myeloma:

• Dosage: 40 mg intravenously on day 1 of each 28-day cycle
• Combined with: Dexamethasone 40 mg orally weekly (20 mg in patients >75 years)
• Indication: Heavily pretreated relapsed/refractory multiple myeloma 3, 4

Important Clinical Considerations for Melphalan

• Administration: IV melphalan must be reconstituted and administered within 60 minutes; solutions are unstable 2
• Common toxicities: Myelosuppression (particularly neutropenia and thrombocytopenia) 2, 5
• Monitoring: Regular blood counts are essential for dose adjustments 2
• Duration of therapy: Continue until stable response is achieved; improvement may continue over many months 2

Flutamide (Not Indicated for Multiple Myeloma)

Flutamide is not used for multiple myeloma treatment but is indicated for prostate cancer:

• Standard dosage: 250 mg orally every 8 hours (750 mg daily)
• Usage: Used in combination with LHRH agonists for advanced prostate cancer
• Monitoring: Liver function tests should be monitored regularly due to risk of hepatotoxicity

Treatment Selection Algorithm for Multiple Myeloma

1. Determine transplant eligibility (age <65-70 years, good performance status, no significant comorbidities)

   • If transplant-eligible: Induction with bortezomib-based regimens followed by high-dose melphalan (200 mg/m²) and ASCT 1
   • If transplant-ineligible: Proceed to step 2

2. Risk stratification (based on cytogenetics and disease characteristics)

   • Standard risk: Consider lenalidomide-dexamethasone or melphalan-based regimens 1
   • High risk: Consider bortezomib-lenalidomide-dexamethasone 1
   • Intermediate risk: Consider bortezomib-melphalan-prednisone 1

3. For elderly patients: Melphalan-prednisone combinations remain a standard option, particularly:

   • VMP (bortezomib-melphalan-prednisone) 1, 5
   • MPT (melphalan-prednisone-thalidomide) 1

The choice between oral and IV melphalan should be based on patient factors, with IV melphalan showing comparable response rates but potentially more severe myelotoxicity 2.