Amino Acid Solutions for 177Lu-Oxodotreotide Premedication: A Tolerance Study

Abstract

Background: The co-infusion of amino acid solutions during peptide receptor radionuclide therapy reduces the tubular reabsorption of 177Lu-oxodotreotide, thus minimizing nephrotoxicity. In our nuclear medicine department, the patients received two different types of amino acid perfusion over time: a commercial solution (CS) containing 10% amino acids, and a 2.5% lysine−arginine (LysArg) hospital preparation, produced by a referral laboratory. The aim of the present study was to analyze the tolerance of the two amino acid solutions. Methods: The patient files were analyzed and double-checked. The study parameters comprised the gender, age, primary tumor site, type of amino acid perfusion, adverse events (AE) and WHO AE grades, antiemetic premedication, creatinine, and serum potassium level. Results: From February 2016 to February 2019, 76 patients were treated, for a total 235 cycles. AEs occurred in 71% of the CS cycles (n = 82/116), versus 18% (n = 21/119) in the LysArg group (p < 0.0001). In the CS group, the AEs were mostly WHO grade 4 (n = 24/82), and mostly grade 1 in the LysArg group (n = 13/21). Poisson regression showed a higher risk of AE overall and of grades 3 and 4 in the females and with CS. The mean creatinine clearance was identical before and after the PRRT cycles, whichever amino acid perfusion was used. Conclusions: The lysine−arginine preparation showed better tolerance than the commercial solution. The change to LysArg reduced the antiemetic premedication from four molecules to one.

Keywords: 177Lu-oxodotreotide; amino acid perfusion; peptide receptor radionuclide therapy; premedication.

Figure 1

Flow-chart representing timeline use of different amino acid solutions (CS: commercial solution; LysArg: L-lysine L-arginine). From February 2016 to February 2019, all patients were treated with CS solution. After November 2017, all patients were treated with LysArg preparation. PPRT consisted of 4 cycles (1 to 4) of [¹¹⁷Lu]oxodotreotide every 8 weeks.

Figure 2

Percentage adverse events (AEs) in all patients (n = 76) treated with the commercial solution (CS) or the lysine–arginine preparation (LysArg) (A), in 10 patients who received both solutions (B) and distribution according to WHO grade (C). Significant levels: * p < 0.05; ** p < 0.01; *** p < 0.001 and **** p < 0.0001. Bars plot SD values.

Figure 3

Relative risk calculated with Poisson regression for (A) all types of AE in the LysArg group, compared to the CS group; (B) all types of AE in the CS only and (C) LysArg only. Determinants were age, gender, number of cycles and presence of liver metastasis.

Figure 4

Relative risk calculated with Poisson regression for grades 3 and 4 in the LysArg group compared to the CS group. Determinants were age, gender, number of cycles and presence of liver metastasis.