Posology for 177Lu-DOTATATE Therapy in Neuroendocrine Tumor: Effectiveness of Dose Reduction and Cycle Delay for Improving Therapy Tolerability.

Approval of 177Lu-DOTATATE for the treatment of neuroendocrine tumors (NETs) requires monitoring for therapeutic efficacy and safety. A retrospective review was conducted on 173 patients who received 177Lu-DOTATATE at the University of Michigan to identify if posology changes would improve therapy tolerance and completion. Patients were followed up to 3 years following their last cycle of treatment to determine long-term adverse events. Dose reduction (from 7.4 GBq to 3.7 GBq) was used in 13 patients, and cycle delay (8±1 wk to >16-week gap) was used in 36 patients, leading to 82% completion of 4 cycles of therapy. Dose reduction led to higher rates for completing all 4 cycles of therapy, whereas cycle delay led to worsened outcomes. Amino acid infusions led to limited adverse events with nausea, vomiting, and fatigue, even with antiemetic prophylaxis. Carcinoid crisis was observed in 1.2% of patients, which was similar to the findings in the NETTER-1 trial. Acute decline in neutrophils and platelets was observed; however, these blood values rebounded. A decline in renal function (4.3 mL/min/1.73 m2 over 4 years compared with untreated patients) suggests a potential long-term risk for renal toxicity; however, it could also be associated with changes in therapy. When adverse events were severe due to underlying disease, dose reduction, or cycle delay did not adequately impact therapy completion, and required further therapy monitoring. Long-term occurrence of myelodysplasia syndrome was 1.8%, comparable to reported occurrences requiring further monitoring. Our analysis reinforces that 177Lu-DOTATATE is an effective, well-tolerated treatment for NETs with low incidences of long-term adverse events.