Salvage Therapy with 177Lu-Octreotate in Patients with Bronchial and Gastroenteropancreatic Neuroendocrine Tumors

Regular therapy with the radiolabeled somatostatin analog Lu-177-octreotate (22.2-29.6 GBq) in patients with gastroentero-pancreatic or bronchial neuroendocrine tumors results in tumor remission in 46% of patients, including minor response. We present the effects of additional therapy with Lu-177-octreotate in patients in whom progressive disease developed after an initial benefit from regular therapy. Methods: Thirty-three patients with progressive disease after an initial radiologic or clinical response were treated with additional cycles of Lu-177-octreotate. The intended cumulative dose of additional therapy was 14.8 GBq in 2 cycles. Responses were evaluated using Southwest Oncology Group criteria, including minor response (tumor size reduction of >= 25% and <50%). Results: Median time to progression (TTP) after regular therapy was 27 mo. In 4 patients, the intended cumulative dose was not achieved (2 had progressive disease, 2 had long-lasting thrombocytopenia). Hematologic toxicity grade 3 was observed in 4 patients, and grade 4, in 1. The median follow-up time was 16 mo (range, 1-40 mo). No kidney failure or myelodysplastic syndrome was observed. Renewed tumor regression was observed in 8 patients (2 partial remission, 6 minor response), and 8 patients had stable disease. Median TTP was 17 mo. Treatment outcome was less favorable in patients with a short TTP after regular cycles. Treatment effects in patients with pancreatic neuroendocrine tumors were similar to those in patients with other gastroenteropancreatic neuroendocrine tumors. Conclusion: Most patients tolerated additional cycles with Lu-177-octreotate well. None developed serious delayed adverse events. Additional cycles with Lu-177-octreotate can have antitumor effects, but effects were less than for the regular cycles. This may be because of a worse clinical condition, more extensive tumor burden, or changed tumor characteristics. We conclude that this salvage therapy can be effective and is safe.