Novel therapeutic approaches in peritoneal metastasis from colorectal cancer
Year: 2019
Type: dissertation
Abstract: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can offer long-term survival in patients with resectable peritoneal metastasis (PM) from colorectal cancer (CRC), a condition with otherwise dismal prognosis.\n\nIn the first part of her PhD work, Ida Storhaug Frøysnes focused on the current treatment for this patient group, investigating outcome and associated prognostic factors following CRS-HIPEC in Norway. There was acceptable morbidity and no 100-day mortality, the 5-year overall survival (OS) and disease-free survival (DFS) were 36% and 14%, respectively, with a median follow-up of 45 months. The only factor associated with OS in multivariable analysis was tumor burden, expressed by the peritoneal cancer index.\n\nAlthough CRS-HIPEC may offer long-term survival to patients with PM-CRC, most patients experience disease recurrence, and novel therapeutic options are needed. MOC31PE immunotoxin was in-house developed to rapidly kill cells expressing the tumor-associated epithelial cell adhesion molecule (EpCAM), which is highly expressed in CRC. In the second part of Frøysnes’ work, MOC31PE immunotoxin was given intraperitoneally for the first time in the phase I/II ImmunoPeCa-trial. The aim was to evaluate safety and toxicity (primary endpoint), pharmacokinetics, neutralizing antibody response, OS and DFS (secondary endpoints). Frøysnes and co-authors reported no dose limiting toxicity, the maximum tolerated dose was not reached, and there was negligible systemic drug absorption. Drug concentrations in peritoneal fluid samples were in the cytotoxic range, and MOC31PE recovered from the peritoneal cavity retained its cytotoxic activity in cell based assays. Three-year OS and DFS were 78% and 33%, respectively. The promising long-term outcome combined with low systemic absorbance, high drug concentration and cytotoxic activity in peritoneal fluid support further investigations of clinical efficacy.
Author: Ida S. Frøysnes
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3208793570