Intraperitoneal chemotherapy with hydroxycamptothecin reduces peritoneal carcinomatosis: results of an experimental study

Abstract

We studied the efficacy and safety of intraperitoneal chemotherapy with hydroxycamptothecin (HCPT) for the treatment of peritoneal carcinomatosis in animal model. Highly metastatic human hepatocellular carcinoma (HCC) cell line HCCLM3 was injected into the peritoneal cavity of 30 nude mice to construct a model of intraperitoneal carcinomatosis, which were randomized into a treatment group and a control group of 15 mice in each group. The former received intraperitoneal injections of HCPT at the dose of 2 mg/kg body weight for 7 days every other week, on weeks 2, 4 and 6; and the latter received the same dose schedule treatment of 0.9% sodium chloride solution. The mice were observed for 8 weeks. Body weight changes, intraperitoneal carcinomatosis, hematological and biochemical parameters were evaluated. On day 56, 14 mice in the treatment group were still alive, compared against 5 in the control group, and the mean survival time was 55 +/- 1 days [95% confidence interval (CI) 54-57 days] versus 43 +/- 4 days (95% CI 34-51 days) (P = 0.002). The tumor weight in the treatment group (0.8 +/- 0.8 g) was significantly smaller than the control group (2.0 +/- 0.8 g) (P = 0.00028). No bloody ascites or diffuse peritoneal carcinomatosis were observed in the treatment group, as compared with 4 mice (26.7%) that developed bloody ascites and 6 mice (40%) which developed diffuse peritoneal carcinomatosis in the control group (P < 0.001). The treatment group had a significantly lower peripheral white blood cell count [(3.18 +/- 1.72) x 10(9) l(-1)] than the control group [(5.08 +/- 2.03) x 10(9 )l(-1)] (P < 0.05), significantly lower serum alpha fetoprotein level (101.22 +/- 20.12 microg/l) than the control group (244.87 +/- 30.24 microg/l) (P < 0.05), and significantly lower serum gamma glutamyl transpeptidase level (12.45 +/- 2.26 U/l) than the control group (20.75 +/- 3.87 U/l) (P < 0.05). No obvious treatment related toxicities were observed. Intraperitoneal injection of HCPT could inhibit tumor progression, reduce the extent of peritoneal carcinomatosis and improve survival of tumor bearing mice.