Safety of multiple repeated cycles of Lu-octreotate in patients with recurrent neuroendocrine tumour.

Purpose: Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET.

Methods: We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles.

Results: We observed no life-threatening adverse events (CTC-4) during Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001).

Conclusion: Therapy with eight or more cycles of Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET.