A review of more than 10 years of published clinical data supports the use of peptide receptor radionuclide therapy (PRRT)-containing regimens as a way of improving outcomes, minimizing toxicity, and reducing the risk of myelodysplastic syndrome and acute leukemia.
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While PRRT has helped patients with gastroenteropancreatic neuroendocrine tumors (GEPNETs) achieve better outcomes, the associated toxicity to bloods cells has limited its use in some clinical settings where clinicians worry about the risk of thrombocytopenia and neutropenia in the short term, and myelodysplastic syndrome and acute leukemia in the long term.
Therefore, researchers led by Murali Kesavan, The University of Western Australia, (Perth, Western Australia), conducted a literature review along with an examination of their own clinical experiences over the last decade to assess the short- and long-term risks of PRRT-chemotherapy for GEPNETs.
A total of 2225 patients across 16 articles were identified and included in their analysis. Of these, 2104 were treated with PRRT monotherapy and 121 were treated with PRRT and chemotherapy. Median follow-up ranged from 6 months to 62 months.
Overall, short-term myelotoxicity was observed in 221 patients (10%), 213 of whom were treated with PRRT monotherapy and 8 of whom were treated with PRRT plus chemotherapy. When patients did experience acute toxicity, it typically manifested as grade 3 or 4 adverse events, often affecting platelets during the first cycle of treatment. Additionally, toxicity manifesting early was easily managed with dose modification or therapy cessation and was ameliorated by appropriate patient selection.
Cases of Myelodysplastic syndrome and acute leukemia were reported in only 32 patients (1.4%). Factors associated with myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (alkylating agents), and prior radiotherapy.
Researchers concluded that early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity, and renders the risk of myelodysplastic syndrome and acute leukemia negligible.
“Given the marked improvement in [disease control rates] since the introduction of PRRT, it is now time to acknowledge that this therapy, if available and considered appropriate, should be ideally administered to GEPNET patients first line, or on progression following long-acting somatostatin analogs (SSA),” they added. “This would not only serve to mitigate significant cumulative myelotoxicity but may be expected to translate into further improvements in response.”
