Comparison of Two Types of Amino Acid Solutions on 177Lu-Dotatate Pharmacokinetics and Pharmacodynamics in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND

177Lu-Dotatate is used in the treatment of somatostatin-receptor-positive inoperable progressive gastroenteropancreatic neuroendocrine tumors. A co-infusion of amino acids (AAs) is administered to prevent renal toxicity.

OBJECTIVE

This study aimed to quantify the impact of two types of AA cocktails on the pharmacokinetics and toxicity of 177Lu-Dotatate.

METHODS

Four injections of 7400 MBq 177Lu-Dotatate were given per patient with administration of either Primene® 10% (containing a cocktail of 20 AAs with 22g of Lysine and 16.8 g of Arginine) or Lysakare® (containing 25 g of Lysine and 25 g of Arginine). Nine blood samples were collected at each cycle. Radioactivity-time data were analyzed according to a population-based model using NONMEM (version 7.4.1). Renal and hematological toxicity was evaluated after each cycle.

RESULTS

1,678 177Lu-Dotatate plasma concentrations versus time were analyzed from 83 consecutive patients with Primene® (n= 45 pts) or Lysakare® (n= 36 pts). Population pharmacokinetic analysis showed that Primene® significantly increased the elimination rate constant of 177Lu-Dotatate as opposed to Lysakare®. Primene® also significantly lowered Lutathera® plasma exposure (AUC) by 34%, whereas Lysakare® increased AUC by 7%. There was no renal toxicity in either case. Lymphopenia significantly correlated with AUC (p=0.021) with a trend towards higher toxicity with Lysakare®.

CONCLUSION

Unlike Primene®, Lysakare® does not increase 177Lu-Dotatate elimination. This difference is associated with a significant impact on AUC. The latter parameter has a high interpatient variability but a low intrapatient variability, which could have important clinical implications for treatment tailoring.