What is the best treatment approach for melanoma in-transit lesions using melphalan?

Best Treatment Approach for Melanoma In-Transit Lesions Using Melphalan

For melanoma in-transit lesions, melphalan is most effectively administered via hyperthermic isolated limb perfusion (ILP), which achieves a complete response rate of approximately 58% compared to 29-33% with isolated limb infusion (ILI). 1

Regional Therapy Options with Melphalan

Isolated Limb Perfusion (ILP)

• Technique: Open surgical access to central venous and arterial blood flow of the limb, isolated by tourniquet and connected to extracorporeal perfusion circuit
• Effectiveness:
  • Complete response rate: 58% (range 25-89%)
  • Overall response rate: 90% (range 64-100%) 1
• Administration:
  • Melphalan is the most commonly used cytotoxic agent
  • Often delivered under hyperthermic conditions to improve efficacy 1
  • Can be combined with actinomycin D (CR 45-65%) or TNF-alpha (CR up to 70%) 1
• Advantages: Higher response rates compared to ILI

Isolated Limb Infusion (ILI)

• Technique: Less invasive approach using percutaneous catheter placement without surgical isolation of vessels
• Effectiveness:
  • Complete response rate: 29-33% 1
  • Overall response rate: 73% 1
• Administration:
  • Melphalan manually infused over approximately 20 minutes
  • Often combined with actinomycin D 1
• Advantages:
  • Simpler procedure than ILP
  • Lower toxicity and morbidity
  • Can be repeated more easily
  • Better tolerated in elderly patients 1

Important Considerations

Patient Selection

• Best for patients with:
  • Unresectable in-transit metastases confined to an extremity
  • Multiple, bulky or rapidly recurring lesions 1
• Not suitable for patients with systemic disease

Toxicity Management

• For ILI: Correction of melphalan dose for ideal body weight decreases severe local toxicity while maintaining complete response rates 2
• Monitor for:
  • Regional toxicity (more common with addition of papaverine) 1
  • Systemic leakage (continuous monitoring recommended) 3

Repeat Treatments

• Repeat ILP with TNF-alpha and melphalan is feasible after previous ILP failure
• Complete response rates for repeat procedures comparable to first procedure (62% vs 65%) 4
• Median limb recurrence-free survival after repeat ILP: 13 months 4

Special Situations

Bulky Lesions

• For large, bulky in-transit metastases, consider adding TNF-alpha to melphalan
• TNF-alpha enhances melphalan uptake and selectively destroys vasculature of large tumors 5, 6
• Complete response rates with TNF-alpha addition: 59-85% 5

Elderly or Frail Patients

• ILI is preferred over ILP due to:
  • Less invasive nature
  • Lower morbidity
  • Better tolerability 1

Pitfalls and Caveats

1. Specialized Centers: These procedures should only be performed in centers with expertise to manage both the procedure and potential complications 1

2. Not for Systemic Disease: Regional therapy with melphalan is limited to patients with metastases confined to an extremity 1

3. Toxicity Risk: Monitor for regional toxicity and systemic leakage during procedure 3

4. Limited Duration: While response rates are high, duration of response may be limited, particularly in sarcoma patients 3

5. Secondary Malignancies: Long-term use of melphalan carries risk of secondary malignancies, including acute leukemia 7

In conclusion, while both ILP and ILI with melphalan are effective options for in-transit melanoma lesions, ILP offers higher complete response rates (58% vs 29-33%) and should be considered the optimal approach when technically feasible and appropriate for the patient's condition.