A retrospective analysis assessing effects of cytotoxic versus cytostatic agents on body mass, nutritional parameters, and performance status in patients with exocrine pancreas cancer enrolled in phase I and II trials.

Abstract

438 Background: The 5-year survival for pancreatic adenocarcinoma is poor, and patients increasingly turn to experimental agents after conventional treatments have failed. Novel chemotherapeutic agents undergo rigorous phase I and II trials to confirm efficacy, safety, tolerability, and optimal dose for entry into late phase trials. Cytostatic therapies are theorized to have an improved tolerability compared to traditional cytotoxic therapies. Methods: This retrospective study compared the tolerability of cytostatic vs cytotoxic therapies in patients with advanced pancreatic cancer who participated in phase I or II trials at a single institution. Nutrition parameters of weight and albumin, performance status, tumor marker CA 19-9 level, and mean tumor dimension defined by RECIST criteria were obtained for patients within four weeks of trial start date and conclusion. Results: 117 patient trials were assessed in final analysis. No statistically significant difference was observed between patients receiving cytostatic and cytotoxic agents with regards to mean weight loss (1.01 vs 1.30 kg; p =.733), decrease in albumin (0.36 vs 0.29 g/dL; p =.397), and percent change in CA 19-9 (-72% vs -76%; p =.882). Results of change in performance status were similar, with mean increase in ECOG (0.63 vs 0.61; p =.948) and decrease in Karnofsky (13 vs 12, p =.709). There was a statistically significant difference in tumor dimension with cytostatic vs cytotoxic agents (18% vs -3%, p =.043). There were no differences in trends between patients enrolled in one trial compared to those enrolled in multiple trials. Conclusions: This study did not show a significant difference between cytostatic and cytotoxic agents in patients with advanced pancreatic adenocarcinoma in early phase trials with regards to nutritional parameters, performance status, or change in CA 19-9. However, there was a statistically significant change in tumor dimension. Thus, cytotoxic agents have similar tolerability to cytostatic agents and may have additional benefit on tumor burden in patients with advanced pancreatic adenocarcinoma.