Is 8 Lutetium-177 (Lu-177) infusions more beneficial than 6 infusions?

Optimal Number of Lutetium-177 (Lu-177) Infusions

For most indications, 6 cycles of Lu-177 is the standard recommended regimen, and there is no clear evidence supporting that 8 infusions provide additional benefit over 6 infusions. 1

Evidence-Based Recommendations for Lu-177 Treatment Regimens

Standard Treatment Protocols

• For prostate cancer: 6 cycles of Lu-177 administered every 6 weeks is the established protocol 1, 2
• For neuroendocrine tumors: 3-5 cycles administered every 6-12 weeks 1
• The FDA-approved regimen for Lu-177-PSMA-617 in metastatic castration-resistant prostate cancer is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to six doses 3

Efficacy and Outcomes

• The VISION trial, which established the efficacy of Lu-177-PSMA-617, used a protocol of 4-6 cycles and demonstrated significant improvement in overall survival (15.3 vs 11.3 months) compared to standard care 2
• No high-quality studies have demonstrated superior outcomes with 8 cycles compared to the standard 6 cycles
• The clinical benefit must be weighed against potential cumulative toxicity with additional cycles

Toxicity Considerations

Hematological Toxicity

• Lu-177 therapy causes predictable hematological toxicity patterns:
  • Platelets, lymphocytes, and neutrophils are affected with most significant impact on neutrophils around 10-11 days post-infusion 1
  • Recovery typically occurs within 12-14 days for platelets and 6-14 days for neutrophils 1
• Additional cycles beyond the standard regimen may increase the risk of:
  • Grade 3/4 neutropenia (occurs in approximately 1% of patients)
  • Grade 3/4 thrombocytopenia (occurs in approximately 2% of patients)
  • Grade 3/4 lymphopenia (occurs in approximately 9% of patients) 1

Monitoring Requirements

• Complete blood count monitoring should be performed weekly starting 2 weeks after administration until recovery 1
• For significant cytopenias, more frequent monitoring is required:
  • Platelet counts at least three times weekly if below 30 × 10^9/L
  • Consider platelet transfusions when count falls below this threshold 1

Special Considerations

Patient Selection

• Treatment decisions should consider:
  • Prior treatment history
  • Performance status
  • Organ function (particularly renal and bone marrow reserve)
  • Tracer uptake on diagnostic scans (e.g., PSMA-positivity for prostate cancer) 2

Potential for Extended Treatment

• In select cases where patients show continued response without significant toxicity, extended treatment beyond 6 cycles might be considered
• However, this should be approached with caution as:
  • Cumulative toxicity may increase with additional cycles
  • There is limited evidence supporting improved outcomes with extended treatment

Conclusion

Based on the most current evidence, the standard 6-cycle regimen of Lu-177 remains the recommended approach for most patients. While some clinicians may consider extending treatment to 8 cycles in select cases showing continued response without significant toxicity, there is no strong evidence that this approach improves overall survival or progression-free survival compared to the standard 6-cycle regimen.