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- Cederkrantz, Elin, et al.
(författare)
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Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients.
- 2015
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Ingår i: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 93:3, s. 569-76
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of (211)At-MX35F(ab')2.
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| 3. |
- Hallqvist, Andreas, 1973, et al.
(författare)
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Intraperitoneal alpha-Emitting Radioimmunotherapy with At-211 in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations
- 2019
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 60:8, s. 1073-1079
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Tidskriftsartikel (refereegranskat)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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