Comparison of Nausea and Vomiting Associated With Amino Acid Formulations Coinfused With Peptide Receptor Radionuclide Therapy

Abstract

Objectives: Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177 Lu-DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177 Lu-DOTATATE. Our program transitioned to compounded L-arginine 2.5%/L-lysine 2.5% in 0.9% NaCl after commercial approval of 177 Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations.Methods: Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177 Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities.Results: Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%).Conclusions: Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.

The evolution of PRRT for the treatment of neuroendocrine tumors; What comes next?

“…Long-term myelodysplasia or leukaemia appears to occur in a little over 2% of patients, although historically, many have been heavily pretreated. Renal toxicity, which is mitigated with concomitant amino acid infusion (20) has been mainly related to Y-90 therapy and is uncommon with Lu-177 (28,29). The diagnosis, management and follow-up of patients with GEP-NETs is detailed in recent ESMO Guidelines (3).…”

“…In addition, a long-term safety follow-up of patients included in the retrospective study showed no lasting relevant hematotoxic effects and no long-term renal toxicity for up to 6 years after the 1 st PRRT. At the present time, it is standard practice to provide renal protection with a 2,5% lysine/arginine infusion which is given concomitantly with the PRRT infusion ( 20 ).…”

A Narrative Review: Analysis of Supplemental Parenteral Nutrition in Adults at the End of Life

“…In fact, some immunomodulatory formulas are actually supplemented with this amino acid; arginine is present in concentrations that range from 0.45 g/100 mL to 1.47 g/100 mL. However, it is difficult to obtain conclusive data on the studies carried out with arginine due to the lack of standardization of the different protocols for use of PN, since although an immunomodulatory function is noted, there is uncertainty as to its beneficial role in patients with septicemia [ 60 , 61 , 62 , 63 ].…”

Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors

“…As mentioned above, aminoacidic infusion is recommended because it notably reduces the radiopharmaceutical’s renal uptake; renal toxicity with [ 177 Lu]Lu-DOTA-TATE is negligible when prophylactic amino acids are used, even in patients with a glomerular filtration rate < 50 mL/min. Moreover, co-infusions of arginine/lysine result in substantially lower rates of nausea/vomiting compared with commercial amino acid formulations designed for parenteral nutrition [ 143 ]. Literature data are also in favor of extending both the amino acid solution infusion time and the amino acid protection to over 2 days, in order to further reduce renal toxicity.…”