Abstract
Ovarian peritoneal carcinomatosis is a pathology for which effective cures are currently lacking. New research protocols seek to eradicate residual micrometastases following cytoreductive surgery by using hyperthermic intraperitoneal chemotherapy (HIPEC) or radioimmunotherapy (RIT). This study aims to first develop alpha-RIT using an anti-CD138 mAb radiolabeled with an alpha-emitter, bismuth-213 ((213)Bi-B-B4) and HIPEC in a nude mouse model and second to compare and combine these techniques. A murine model of postoperative ovarian peritoneal carcinomatosis was established. A pilot group of six mice received an intraperitoneal injection of luciferase-tagged SHIN-3 cells and bioluminescence was measured every day. Cytoreductive surgery was performed at day 14 (n = 4) and 29 (n = 2). Because the residual bioluminescence signal measured after surgery was equivalent to that obtained 3 days after the graft, HIPEC or alpha-RIT treatments were applied 3 days after the graft. Ten mice were treated by HIPEC with cisplatine (37.5 mg/mL), 11 with 7.4 MBq of (213)Bi-B-B4, seven with 11.1 MBq of (213)Bi-B-B4, and 10 mice were treated with the combined therapy (HIPEC + 7.4 MBq of (213)Bi-B-B4). Eleven mice received no treatment. Bioluminescence imaging and survival were assessed. Alpha-RIT 7.4 MBq and 11.1 MBq significantly improved survival (p = 0.0303 and p = 0.0070, respectively), whereas HIPEC and HIPEC + alpha-RIT treatments did not significantly ameliorate survival as compared to the control group. Survival was significantly increased by alpha-RIT treatment in mice with peritoneal carcinomatosis of ovarian origin; however, HIPEC alone or in combination with alpha-RIT had no significant effect.
Highlights
Epithelial ovarian carcinoma (EOC) is the leading cause of mortality linked to gynecological cancer in France with 3357 deaths in 2006 [1]
This study aims to target the residual pathology of ovarian peritoneal carcinomatosis by means of a monoclonal humanized anti-CD138 antibody radiolabeled with an alpha-particle emitter and to compare and combine this treatment with hyperthermic intraperitoneal chemotherapy (HIPEC)
The curves relating to HIPEC come close to matching those of the mice receiving no treatment
Summary
Epithelial ovarian carcinoma (EOC) is the leading cause of mortality linked to gynecological cancer in France with 3357 deaths in 2006 [1]. A recent French phase III and IV multicenter retrospective cohort study of 566 patients treated with HIPEC found mortality and morbidity levels of 0.8 and 31.3%, respectively, for advanced and recurrent ovarian cancer [7]. Another multicenter retrospective study estimated that overall 4-year survival rates for patients treated with HIPEC was 75.6% compared to 19.4% for the control group [8], and recently a retrospective observational multi-institutional study was conducted showing that HIPEC results in encouraging survival rates for patients treated for a first relapse of ovarian cancer [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
