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

Artikel i vetenskaplig tidskrift
Författare 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
Publicerad i Journal of Nuclear Medicine
Volym 60
Nummer/häfte 8
Sidor 1073-1079
ISSN 0161-5505
Publiceringsår 2019
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi
Sidor 1073-1079
Språk en
Länkar dx.doi.org/10.2967/jnumed.118.22038...
Ämnesord astatine, alpha particle, intraperitoneal, ovarian cancer, phase I, monoclonal-antibodies, recurrence, dosimetry, survival, duration, therapy, trial, hmfg1, women, 2nd, Radiology, Nuclear Medicine & Medical Imaging
Ämneskategorier Cancer och onkologi

Sammanfattning

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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