A case report of acute carcinoid heart failure during lutetium-177 dotatate-triapine treatment for well-differentiated neuroendocrine tumors.
Source: PubMed, NCBI / U.S. National Library of Medicine
Well-differentiated neuroendocrine tumors (NETs) have a high indolent local progression rate when resistance develops to biologic or cytotoxic chemotherapy. Radiopharmaceuticals like single-agent [Lu]lutetium-177 dotatate confer a 17% objective NET partial response rate with prolongation of progression-free survival. The patient, a 69-year-old man with gastroenteropancreatic NET with liver metastases and known chronic systolic heart failure (HF), had received octreotide then everolimus therapy prior to enrollment. At entry, his disease status was complicated by bilateral edema to his thighs worsening over a 4-week period and an echocardiogram showing right heart hypertrophic cardiomyopathy with an ejection fraction of 40%. [Ga]Gallium-68 dotatate positron emission tomography identified tumors in the lung, liver, spleen, and axial skeleton. The phase I clinical trial involved intravenous [Lu]lutetium-177 dotatate (day 1) given with concurrent once daily oral triapine (days 1-14) given as a radiosensitizer that repeated every 8 weeks for four cycles (NCT04234568); [Lu]lutetium-177 dotatate requires concomitant treatment with 1 L of an isotonic amino acid salt solution, usually administered over a 4-h period around the radiopharmaceutical. On cycle 1 day 8, the patient was found unresponsive at home and efforts to resuscitate him were unsuccessful. Autopsy on cycle 1 day 9 revealed acute HF in the setting of HF complicated by carcinoid heart disease, measurable radionuclide orga
Abstract
Well-differentiated neuroendocrine tumors (NETs) have a high indolent local progression rate when resistance develops to biologic or cytotoxic chemotherapy. Radiopharmaceuticals like single-agent [Lu]lutetium-177 dotatate confer a 17% objective NET partial response rate with prolongation of progression-free survival. The patient, a 69-year-old man with gastroenteropancreatic NET with liver metastases and known chronic systolic heart failure (HF), had received octreotide then everolimus therapy prior to enrollment. At entry, his disease status was complicated by bilateral edema to his thighs worsening over a 4-week period and an echocardiogram showing right heart hypertrophic cardiomyopathy with an ejection fraction of 40%. [Ga]Gallium-68 dotatate positron emission tomography identified tumors in the lung, liver, spleen, and axial skeleton. The phase I clinical trial involved intravenous [Lu]lutetium-177 dotatate (day 1) given with concurrent once daily oral triapine (days 1-14) given as a radiosensitizer that repeated every 8 weeks for four cycles (NCT04234568); [Lu]lutetium-177 dotatate requires concomitant treatment with 1 L of an isotonic amino acid salt solution, usually administered over a 4-h period around the radiopharmaceutical. On cycle 1 day 8, the patient was found unresponsive at home and efforts to resuscitate him were unsuccessful. Autopsy on cycle 1 day 9 revealed acute HF in the setting of HF complicated by carcinoid heart disease, measurable radionuclide organ uptake, and widely disseminated NET with 50% tumor lysis. This case reports the rare complication of an acute exacerbation of carcinoid-associated HF by the [Lu]lutetium-177 dotatate-triapine combination. The cause of the acute cardiac decompensation could be related to the marked tumor response to treatment and/or contributions of the renoprotective amino acid infusion.