Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC

Abstract

Therapy with [(90)Y-DOTA(0), Tyr(3)]-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 (177)Lu-labeled somatostatin analogs showed less nephrotoxicity. We initiated a prospective study with (177)Lu-DOTATOC in patients with relapsed neuroendocrine tumors after (90)Y-DOTATOC treatment.

Methods: Twenty-seven patients, pretreated with (90)Y-DOTATOC, were included. The mean time between the last treatment with (90)Y-DOTATOC and (177)Lu-DOTATOC was 15.4 +/- 7.8 mo (SD). All patients were injected with 7,400 MBq of (177)Lu-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 micromol/L to 100 +/- 44 micromol/L (P < 0.0001), after (90)Y-DOTATOC therapy. The mean hemoglobin level dropped from 131 +/- 14 to 117 +/- 13 g/L (P < 0.0001) after (90)Y-DOTATOC therapy. (177)Lu-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: (177)Lu-DOTATOC therapy in patients with relapse after (90)Y-DOTATOC treatment is feasible, safe, and efficacious. No serious adverse events occurred.