Speaker
Dr
Albertsson Per
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Description
Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. Following extensive preclinical work with α-particle emitting astatine-211 (211At), we performed a phase I trial in epithelial ovarian cancer (EOC). This was a first-in-class intraperitoneal (i.p.) α-particle therapy and the first in human study using the conjugate 211At-MX35, a murine monoclonal F(ab’)2 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 EOC, achieving a second complete or near complete response with chemotherapy received i.p. treatment with escalating (20 to 215 MBq/L) activity concentrations of 211At-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 α-particle irradiation with no observed hematological toxicity. One grade 3 fatigue, and one grade 4 intestinal perforation during catheter implantation was observed. Four patients had a survival >6 years, one of whom did not relapse. At progression chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 months with a 1-, 2-, 5-, and 10-year survival of 100%, 83%, 50% and 25%.
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 micro-tumors 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.
| Funding Agency | Swedish Research Council; the Swedish Cancer Society; the King Gustav V Clinic Research Foundation |
|---|---|
| Email Address | andreas.hallqvist@gu.se |
| Presentation Type | Contributed Oral |
Primary authors
Dr
Albertsson Per
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Dr
Andreas Hallqvist
(Dept. of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden)
Co-authors
Dr
Andersson Håkan
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Dr
Bergmark Karin
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Mr
Bäck Tom
(Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Dr
Dahm-Kähler Pernilla
(Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Dr
Holger Jensen
(PET and Cyclotron unit, Copenhagen University Hospital)
Prof.
Hultborn Ragnar
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Prof.
Jacobsson Lars
(Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Dr
Johansson Mia
(Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden)
Stig Palm
(University of Gothenburg)
Dr
Sture Lindegren
(Departemnt of Radiation Physics, Institute of clinical Sciences Sahlgrenska Academy at Gotehnburg University)
