Peng-Cheng Li1, Liang-Dong Chen, Fang Zheng, Yan Li. 1. Department of Oncology, Zhongnan Hospital and Cancer Center of Wuhan University, 169 Donghu Road, Wuhan 430071, Hubei Province, China.
Abstract
PURPOSE: We studied the efficacy and safety of intraperitoneal chemotherapy with hydroxycamptothecin (HCPT) for the treatment of peritoneal carcinomatosis in animal model. METHODS: 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. RESULTS: 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. CONCLUSIONS: Intraperitoneal injection of HCPT could inhibit tumor progression, reduce the extent of peritoneal carcinomatosis and improve survival of tumor bearing mice.
PURPOSE: We studied the efficacy and safety of intraperitoneal chemotherapy with hydroxycamptothecin (HCPT) for the treatment of peritoneal carcinomatosis in animal model. METHODS: Highly metastatic humanhepatocellular 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. RESULTS: 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. CONCLUSIONS: Intraperitoneal injection of HCPT could inhibit tumor progression, reduce the extent of peritoneal carcinomatosis and improve survival of tumor bearing mice.
Authors: Sebastián Rufián; Francisco C Muñoz-Casares; Javier Briceño; Carlos J Díaz; María J Rubio; Rosa Ortega; Rubén Ciria; Manuel Morillo; Enrique Aranda; Jordi Muntané; Carlos Pera Journal: J Surg Oncol Date: 2006-09-15 Impact factor: 3.454