Dosing 225 Ac-DOTATOC in patients with somatostatin-receptor-positive solid tumors: 5-year follow-up of hematological and renal toxicity.

Autor: Kratochwil C; Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany. clemens.kratochwil@med.uni-heidelberg.de., Apostolidis L; Department of Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg University Hospital, Heidelberg, Germany., Rathke H; Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany., Apostolidis C; European Commission, Joint Research Centre (JRC), Karlsruhe, Germany., Bicu F; Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany., Bruchertseifer F; European Commission, Joint Research Centre (JRC), Karlsruhe, Germany., Choyke PL; Molecular Imaging Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA., Haberkorn U; Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.; Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (dkfz), Heidelberg, Germany.; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany., Giesel FL; Department of Nuclear Medicine, Heidelberg University Hospital, INF 400, 69120, Heidelberg, Germany.; Department of Nuclear Medicine, University Hospital Düsseldorf, Düsseldorf, Germany., Morgenstern A; European Commission, Joint Research Centre (JRC), Karlsruhe, Germany.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2021 Dec; Vol. 49 (1), pp. 54-63. Date of Electronic Publication: 2021 Aug 26.
DOI: 10.1007/s00259-021-05474-1
Abstrakt: Purpose: The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of 225 Ac-DOTATOC in patients treated for somatostatin-receptor-expressing cancers.
Methods: 225 Ac-DOTATOC was administered to thirty-nine patients with various somatostatin-receptor-positive tumors. Baseline and follow-up 68 Ga-DOTATOC PET/CT, lab tests, and renal scintigraphy were obtained. Patients received long-term follow-up either at the local cancer center or in close collaboration with external oncologists. Acute and chronic hematological toxicity was evaluated quantitatively over time. Long-term follow-up of creatinine was used to approximate the annual loss of estimated GFR (eGFR).
Results: Dose-dependent acute hematological toxicity was seen at single doses above 40 MBq or repeated doses greater than approximately 20 MBq 225 Ac-DOTATOC at 4 month intervals. Treatment-related kidney failure occurred in 2 patients after a delay of >4 years but was independent of administered radioactivity, and other clinical risk factors were important contributors to renal decline. In general, the annual decline of eGFR among patients did not follow a clear dose-effect relationship even in patients with previous β-therapy. An average eGFR-loss of 8.4ml/min (9.9%) per year was observed which is similar to the experience with β-therapy studies.
Conclusion: Treatment activities of approx. 20 MBq per cycle (4 monthly repetition) and cumulative doses up to 60-80 MBq generally avoided both acute and chronic grade 3/4 hematotoxicity in patients with advanced stage malignancies. Chronic renal toxicity was observed at these doses, but pre-existing renal risk factors were important co-factors. These data represent a starting point for additional research to more precisely define safety thresholds of 225 Ac-DOTATOC.
(© 2021. The Author(s).)
Databáze: MEDLINE
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