Effects of amino acid co-infusion on increased catecholamine symptoms in metastatic pheochromocytoma patients treated with 177Lu-DOTATATE

76 Introduction: Pheochromocytoma/paraganglioma (PHEO/PGL) produces excessive catecholamines such as epinephrine and norepinephrine which causes labile hypertension, tachycardia, and flushing. Lu-177-DOTATATE is a radiolabeled somatostatin analog that is FDA approved for somatostatin receptor-positive neuroendocrine tumors and being tested in PHEO/PGL, known to overexpress somatostatin receptors. Amino acid solutions containing lysine/arginine (L/A) are routinely co-administered with Lu-177-DOTATATE for renal radioprotection, although solutions containing other amino acids are frequently used. Objective: In patients with PHEO/PGL, the use of non-selective amino acid solutions could lead to a unique problem, as the phenylalanine (PHE) and tyrosine (TYR) found in these products are part of the catecholamine biosynthesis pathway. It is therefore possible that these amino acid solutions can increase sympathetic symptoms in PHEO/PGL. An analysis is performed to evaluate this hypothesis. Methods: Thirteen patients with metastatic PHEO/PGL were enrolled in a prospective therapeutic trial using Lu-177-DOTATATE and were given up to 4 cycles q8 weeks apart. Patients treated before 10/30/18 received Clinisol 15% (Baxter) diluted to 10.4% in 2.2L volume starting 60 minutes prior to Lu-177-DOTATATE infusion, while those treated starting 10/31/18 received a 2.5% L/A solution 30 minutes prior. Patients were observed for catecholamine-related symptoms and vital signs were obtained. A particular Lu-177-DOTATATE administration was excluded from analysis if BP or HR medications were given after start of amino acids and prior to Lu-177-DOTATATE infusion. Results: Clinisol 15% contains 1.04g of phenylalanine and 0.039g of tyrosine per 100mL solution, meaning that in 60 minutes, patients received approximately 2.34g of phenylalanine and 0.088g of tyrosine with an infusion rate of 325 ml/hr. From the 13 enrolled patients, there were a total of 37 individual administrations of amino acids, of which 29 (78.3%) were evaluable. Of the 29 evaluable administrations, 23 were done with Clinisol and 6 with L/A amino acids. In the Clinisol group, the mean baseline heart rate (HR) and systolic blood pressure (SBP) were 74.6 (range 51 to 99) and 116.8 (range 96 to 150), respectively, which is comparable to the group who received L/A with mean HR of 79.7 (range 56 to 103) and SPB 118.3 (range 86 to 139). Just prior to Lu-177-DOTATATE infusion, the mean change in HR and SBP was +3.5 (range -12 to +21) and +9.6 (range -9 to +39) in the Clinisol group, which is increased compared to the L/A group with mean change in HR and SPB of -2.2 (range -8 to 4) and +1.5 (range -8 to +10), respectively. In catecholamine secretors, the mean HR and SBP changed by +3.5 (range -12 to +19) and +14.8 (range -14 to +39) in the Clinisol group but did not exhibit the same degree of change in the L/A group with mean HR and SPB changed by -6.0 (range -6 to -4) and +4.5 (range -1 to 10), respectively. In non-secretors, this effect is not seen with mean HR and SBP change of +3.5 (range -2 to +21) and -0.3 (range -9 to +14) in the Clinisol group, and -0.3 (range -5 to +4) and 0 (range -8 to +8) in the L/A group, respectively. There were no clinically significant developments or changes in catecholamine-related symptoms during the amino acid infusion. Conclusions: Preliminary analysis suggests that there is an increase in HR and SBP after 60 minutes of PHE/TYR-containing amino acid administration which, in patients with PHEO/PGL, may represent increased sympathetic effects from temporarily boosted catecholamine biosynthesis. This is supported by the finding that increased HR and SPB is seen primarily in catecholamine secretors when using Clinisol but not with the 2.5% Lys/Arg solution. Other factors which may have contributed such as anxiety and nausea cannot be ruled out, although subgroup analysis suggests that these others factors alone does not account for the observed findings.