When to continue Lutetium-177 (Lu-177) infusions after two infusions?

Continuing Lu-177 Infusions Beyond Two Cycles

Lu-177 therapy should be continued for a total of three to five cycles at 6-12 week intervals to achieve optimal therapeutic benefit, as recommended by international guidelines. 1

Standard Treatment Protocol

• The standard treatment protocol for Lu-177-DOTATATE/DOTATOC therapy involves administering 5.55-7.4 GBq (150-200 mCi) per cycle 1
• Guidelines recommend completing three to five total cycles of Lu-177 therapy with 6-12 week intervals between treatments 1
• Stopping after only two cycles would deliver suboptimal cumulative radiation dose to tumor tissue, potentially compromising therapeutic efficacy 1

Evidence Supporting Continuation

• Response assessment typically occurs after completing the full treatment course (3-5 cycles), not after just two cycles 1
• Objective tumor responses in gastroenteropancreatic NETs range from 9% to 29% partial responses and 2% to 6% complete remissions when the full treatment course is administered 1
• Patients with high somatostatin receptor tumor expression show significantly higher objective responses and longer survival when completing the full treatment regimen 1

Response Assessment

• The first follow-up examination to assess response should occur 3 months after completing the full treatment course 1
• Response evaluation includes:
  • Functional and morphological imaging 1
  • Biochemical markers 1
  • Symptomatic response 1
  • Quality of life measures 1
• Post-therapeutic Lu-177-DOTATATE scans after each cycle provide valuable information on uptake intensity and tracer localization, helping assess response to prior cycles 1

Monitoring Between Cycles

• Complete blood count should be performed every 2-4 weeks between cycles 1
• Renal and liver function tests should be evaluated before confirming subsequent cycles 1
• If blood values fall below acceptable limits, options include:
  • Administering a lower activity in subsequent cycles 1
  • Extending the interval between cycles 1
  • In severe cases, interrupting therapy 1

Safety Considerations

• The kidney and bone marrow are the critical organs at risk during Lu-177 therapy 1
• Regular assessment of renal function is essential, including serum creatinine levels and creatinine clearance 1
• For high-risk patients (hypertension, diabetes, single kidney, prior nephrotoxic chemotherapy), more precise methods to assess renal function are recommended 1
• Extended treatment with Lu-177 has not been associated with increased grade 3-4 toxicity in recent studies 2

Special Considerations for Extended Treatment

• Recent evidence shows that extended therapy beyond 6 cycles is feasible with favorable safety profiles 2
• Patients receiving extended Lu-177 treatment experienced a favorable median survival of 31.3 months from first administration 2
• Extended treatment can be administered as continuous therapy or as a rechallenge after a treatment break 2

Conclusion

Continuing Lu-177 therapy beyond two cycles to complete the recommended 3-5 cycle protocol is essential for maximizing therapeutic benefit. The decision to continue should be guided by ongoing assessment of tumor response, patient tolerance, and monitoring of potential toxicities, particularly to the kidneys and bone marrow.