Myelotoxicity of Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Decade of Experience

Aim: This review of the literature, and the authors' own decade of experience with lutetium-177-octreotate-capecitabine +/- temozolomide peptide receptor radionuclide therapy (PRRT)-chemotherapy of GEPNETs, analyses the risk of both short- and long-term hematotoxicity. Background: Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with PRRT in heavily pretreated patients with a history of exposure to alkylating agents. Commenced 15 years ago, PRRT is now becoming established as first-and second-line therapy for gastroentero pancreatic neuroendocrine tumors (GEPNETs), and early treatment minimizes myelotoxicity, which is the most significant potential adverse event following PRRT. Results: Sixteen key articles involving primary research were identified. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combined with chemotherapy). The average age of patients in these studies ranged from53 to 64 years with median duration of follow-up ranging from6 to 62months. Short-term myelotoxicity was observed in 221 patients (10%), occurring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combinedwith chemotherapy. Acute toxicity manifested asmodest self-limited grade 3/4 toxicity (CTCAE orWHO), most often affecting platelets during the first cycle of treatment. Toxicity manifesting early was easily managed with dose modification or therapy cessation and was ameliorated by appropriate patient selection. MDS/AL was a rare stochastic event occurring in 32 (1.4%) patients. Where bone marrow biopsy was performed, cases ofMDS displayed cytogenetic abnormalities, consistent with secondaryMDS. Factors associated with myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (alkylating agents), and prior radiotherapy. Conclusion: Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity, and renders the risk of MDS and AL negligible.