Renal and hematological toxicity in patients of neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-DOTATATE

Abstract

Purpose: Peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE is an efficient new treatment option in patients with neuroendocrine tumors (NETs), with low risk of toxicity. Since the kidneys are critical organs in PRRT, renal function is known to deteriorate after PRRT. We analyzed the decline in glomerular filtration rate (GFR), increase in serum creatinine (SCr), and changes in hemogram parameters between pretherapy and at least 6 months after last cycle post-therapy with (177)Lu-DOTATATE.

Methods: Forty-seven patients with NETs received 2-6 cycles of (177)Lu-DOTATATE, leading to a total renal radiation absorbed dose of 12.5 ± 4.1 Gy. All renal dose estimates were calculated with the help of OLINDA/EXM software. All patients were infused with renal protective amino acids during the administration of the radiopharmaceuticals. In this study, we used GFR that was estimated by in vitro method using (99m)Tc-DTPA and SCr to assess renal toxicity.

Results: The patients were administered a mean cumulative activity of 20.1 ± 6.74 GBq of (177)Lu-DOTATATE. There was a significant decrease in GFR from 86.8 ± 15.4 mL/1.73 m(2)/min to 66.1 ± 14.5 mL/1.73 m(2)/min and rise in SCr from 0.86 ± 0.19 mg/dL to 1.0 ± 0.2 mg/dL with treatment. Patients with WHO grade 1 renal toxicity (group 2) at baseline demonstrated an increase in SCr that was significantly higher compared with patients with normal baseline creatinine levels (group 1). No serious acute or remote adverse events were recorded. Self-limiting serious hematological toxicity was observed in 2 patients.

Conclusions: The decline in renal function as measured by in vitro GFR tends to be of greater magnitude in patients with baseline impaired renal function than in patients with preserved renal function after PRRT. Hematologic toxicity is relatively rare and can be managed conservatively when encountered.