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Intraperitoneal alpha-Emitting Radioimmunotherapy with At-211 in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations

Journal article
Authors Andreas Hallqvist
Karin Bergmark
Tom Bäck
Håkan Andersson
Pernilla Dahm-Kähler
Mia Johansson
Sture Lindegren
H. Jensen
Lars Jacobsson
Ragnar Hultborn
Stig Palm
Per Albertsson
Published in Journal of Nuclear Medicine
Volume 60
Issue 8
Pages 1073-1079
ISSN 0161-5505
Publication year 2019
Published at Institute of Clinical Sciences, Department of Radiation Physics
Institute of Clinical Sciences, Department of Oncology
Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 1073-1079
Language en
Links dx.doi.org/10.2967/jnumed.118.22038...
Keywords astatine, alpha particle, intraperitoneal, ovarian cancer, phase I, monoclonal-antibodies, recurrence, dosimetry, survival, duration, therapy, trial, hmfg1, women, 2nd, Radiology, Nuclear Medicine & Medical Imaging
Subject categories Cancer and Oncology

Abstract

Eliminating microscopic residual disease with alpha-particle radiation is theoretically appealing. After extensive preclinical work with alpha-particle-emitting At-211, we performed a phase I trial with intraperitoneal alpha-particle therapy in epithelial ovarian cancer using At-211 conjugated to MX35, the antigen-binding fragments-F(ab')(2)-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of At-211-MX35 F(ab')(2). Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the alpha-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.

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Denna text är utskriven från följande webbsida:
http://www.gu.se/english/research/publication/?publicationId=282819
Utskriftsdatum: 2019-11-19