Nephrotect

Treatment administration protocol: Ondansetron (8 mg; GlaxoSmithKline, London, UK) was administered by i.v. 30 min before amino acid (AA) administration. The AA infusion was to prevent the development of delayed renal toxicity. The slow intravenous infusion of AA (1500 mL; Vamin 18 and Nephrotect; Fresenius Kabi, Bad Homburg, Germany) were carried out for 1.0–1.5 h, then ⁹⁰Y DOTATATE was added via an infusion pump system with a mean speed of 150 mL/h. and was continued for a approx. 20–25 min. Every subject was treated at intervals of 8–12 weeks. The treatment interval could be extended to 16 weeks in patients with longer continuing subacute hematologic adverse events (AEs). All subjects with at least two sessions of PRRT were included in the study.

The patients were administered intravenous infusions of [¹⁷⁷Lu]Lu-DOTATATE with the activity of 7.4 GBq or tandem treatment with [⁹⁰Y]Y-DOTATATE + [¹⁷⁷Lu]Lu-DOTATATE with the activity of 1.85GBq + 1.85 GBq respectively (ItraPol and LutaPol, manufactured by the National Centre for Nuclear Research, Radioisotope Centre POLATOM, Otwock, Poland) (a solution containing radiopharmaceuticals in 100 mL of 0.9% NaCl, a 20-min infusion). The assessment of the morphological and biochemical parameters was performed one day before and two days after radioisotope administration. The patients also received the infusions of 10% amino acid solution (Nephrotect, Fresenius Kabi) (1000 mL on Day 1 and 500 mL on Day 2) and Ringer’s solution (500 mL on Day 1 and 500 ml on Day 2) (Table 1). The treatment with long-acting somatostatin analogues (octreotide—Sandostatin LAR; Novartis and lanreotide autogel-Somatuline; Ipsen) had been discontinued at least four weeks prior to PRRT administration. Previous chemotherapy had to be finished at least three months before.

A fractionated treatment protocol was used with four doses of ⁹⁰Y-DOTA-TOC in 12-week intervals. Activity of each dose was 3.7 GBq (100 mCi). ⁹⁰Y-DOTA-TOC was manufactured by Polatom (Poland). The preparation of ⁹⁰Y-DOTA-TOC was administered intravenously over 20 min. To minimize radiation exposure of the kidneys, an intravenous amino acid solution, Nephrotect (Fresenius Kabi, Germany) was infused intravenously with the flow rate of 150 mL/h. The infusion was initiated 2 h before ⁹⁰Y-DOTA-TOC infusion and continued over 6 h after ⁹⁰Y-DOTA-TOC administration (Bodei et al. 2013 (link)). Altogether, the administered volume of amino acid solution was 1,000–1,400 mL.
Before each course of PRRT, as well as 3 months after the last course of PRRT, physical examination of the patient was performed, and following laboratory measurements were obtained: blood counts, creatinine, urea, transaminases, electrolytes, Tg and anti-thyroglobulin antibodies (aTg). These measurements (except Tg and aTg) were repeated 24 h and 3 weeks after ⁹⁰Y-DOTA-TOC administration for the evaluation of toxicity. Final evaluation of laboratory data was performed 1 year after the last PRRT.
In addition, 3 months and 1 year after the last PRRT following imaging procedures were repeated: SRS, US of the neck and CT of the chest and neck. Imaging parameters were the same as at the initial evaluation.