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Treatment with ¹⁷⁷Lu-DOTATOC of Patients with Relapse of Neuroendocrine Tumors After Treatment with ⁹⁰Y-DOTATOC

¹ Institute of Nuclear Medicine, University Hospital, Basel, Switzerland
² Department of Radiation Physics, Göteborg University, Göteborg, Sweden
³ Division of Radiological Chemistry, University Hospital, Basel, Switzerland

Therapy with [⁹⁰Y-DOTA⁰, Tyr³]-octreotide (DOTATOC, where DOTA = tetraazacyclododecane tetraacetic acid and TOC = D-Phe-c(Cys-Tyr-D-Trp-Lys-Thr-Cys)-Thr(ol)) is established for the treatment of metastatic neuroendocrine tumors. Nevertheless, many patients experience disease relapse, and further treatment may cause renal failure. Trials with ¹⁷⁷Lu-labeled somatostatin analogs showed less nephrotoxicity. We initiated a prospective study with ¹⁷⁷Lu-DOTATOC in patients with relapsed neuroendocrine tumors after ⁹⁰Y-DOTATOC treatment. Methods: Twenty-seven patients, pretreated with ⁹⁰Y-DOTATOC, were included. The mean time between the last treatment with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATOC was 15.4 ± 7.8 mo (SD). All patients were injected with 7,400 MBq of ¹⁷⁷Lu-DOTATOC. Restaging was performed after 8–12 wk. Hematotoxicity or renal toxicity of World Health Organization grade 1 or 2 was not an exclusion criterion. Results: Creatinine levels increased significantly, from 66 ± 14 µmol/L to 100 ± 44 µmol/L (P < 0.0001), after ⁹⁰Y-DOTATOC therapy. The mean hemoglobin level dropped from 131 ± 14 to 117 ± 13 g/L (P < 0.0001) after ⁹⁰Y-DOTATOC therapy. ¹⁷⁷Lu-DOTATOC therapy was well tolerated. No serious adverse events occurred. The mean absorbed doses were 413 ± 159 mGy for the whole body, 3.1 ± 1.5 Gy for the kidneys, and 61 ± 5 mGy for the red marrow. After restaging, we found a partial remission in 2 patients, a minor response in 5 patients, stable disease in 12 patients, and progressive disease in 8 patients. Mean hemoglobin and creatinine levels did not change significantly. Conclusion: ¹⁷⁷Lu-DOTATOC therapy in patients with relapse after ⁹⁰Y-DOTATOC treatment is feasible, safe, and efficacious. No serious adverse events occurred.

Key Words: ¹⁷⁷Lu-DOTATOC • ⁹⁰Y-DOTATOC • radionuclide therapy • somatostatin • neuroendocrine tumors

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