Development of Drug Resistance in Colon Cancer Patients Contributed to Failure of Oxaliplatin-based HIPEC PRODIGE 7 Trial
LONG BEACH, Calif., May 29, 2020 /PRNewswire/ -- Investigators at MedStar Washington Hospital Center and Nagourney Cancer Institute report the results of a study that examined the impact of prior FOLFOX chemotherapy exposure on Oxaliplatin resistance as a potentially important contributing factor for the PRODIGE 7 clinical trial's failure to improve progression free or overall survival in colon cancer patients who received post-operative HIPEC. The PRODIGE 7 study reported in 2018 is a multi-center, phase III trial that randomized 265 colon cancer patients to observation or HIPEC following six cycles of systemic chemotherapy.
The investigators applied ex vivo analysis of programmed cell death (EVA/PCD), a platform that examines drug induced cell death (apoptotic & non-apoptotic) in 3-dimensional organoids from surgical specimens using morphology, staining characteristics and metabolic endpoints to compare Oxaliplatin activity in previously treated and chemo naïve patient's tumor specimens.
A data query of the Nagourney Cancer Institute database identified 87 colon cancer patients of whom 33 were previously treated and 54 chemo-naïve. When Oxaliplatin activity was compared, the previously treated patient's tumors were found significantly more Oxaliplatin resistant than the untreated patient's tumors (p=0.002) with the degree of resistance trending even higher in patients who had received their last chemotherapy within 2 months of EVA/PCD analysis.
"Our results suggest that residual disease following systemic FOLFOX therapy may have been selected for Oxaliplatin resistance thereby blunting the impact of additional Oxaliplatin exposure upon progression free and overall survival even under the conditions of HIPEC administration," said Dr. Nagourney.
A second analysis compared the impact of prior FOLFOX exposure on the activity of Irinotecan and Mitomycin C. When previously treated and chemo naive patients were compared, the investigators did not identify significant differences between chemo naïve and previously treated patients for Irinotecan and Mitomycin C, suggesting that Oxaliplatin resistance may not extend to other classes of cytotoxics.
"To improve outcomes, future strategies may need to examine other classes of drugs, improve patient selection or consider HIPEC administration earlier in the course of therapy, before drug resistance has developed," added Dr. Nagourney.
About the MedStar Washington Hospital Center
MedStar Washington Hospital Center is an internationally recognized tertiary care center, where Dr. Paul Sugarbaker and associates have played a seminal role in the development and application of HIPEC therapy for the treatment of advanced peritoneal malignancies.
Nagourney Cancer Institute
The Nagourney Cancer Institute is a clinical research center that has pioneered the study of human tumor tissue for individualized cancer patient drug selection and has facilitated cancer drug discovery.
SOURCE Nagourney Cancer Institute