In vitro pharmalogic rationale for intraperitoneal regional chemotherapy

A multicentric randomized study that compared patients who received intrahepatic arterial infusion (HAI) to a group of patients who did not receive HAI (control group) was performed for unresectable hepatic metastases from primary colorectal carcinoma. One hundred sixty-six patients were assigned randomly to HAI of floxuridine (5 fluoro-2'deoxyuridine [FUDR]) 0.3 mg/kg/d for 14 days every 4 weeks or to the control group; this latter group, depending on the investigator's choice, was either under observation or received systemic fluorouracil (5-FU). The same regimen of systemic 5-FU also was administered to the HAI group in the event of extrahepatic progression. No crossover from the control group to the HAI group was permitted. The mean duration of follow-up was 54 months (range, 31 to 72), and 163 patients were analyzed. A significant improvement was observed in the survival rate for the 81 patients assigned to HAI group (P less than .02) with a 1-year survival rate of 64% versus 44% in the control group (82 patients). The 2-year survival rate was 23% versus 13%. The median survival was 15 months versus 11 months for the HAI group and the control group, respectively. Survival was better for patients with a less than 30% liver involvement, and for those treated in more specialized centers. The hepatotoxic effects of HAI were observed in 47 patients (chemical hepatitis [n = 28], and biliary sclerosis [n = 19]). The 1-year rate of sclerosing cholangitis was equal to 25%. Gastrointestinal toxicity was infrequent and consisted of gastritis or diarrhea. Therapy with HAI of FUDR improves the survival of patients with liver metastases over colorectal carcinoma. However, the methods that are used to diminish the toxicity of HAI and efficient systemic chemotherapy, such as a combination of 5-FU and leucovorin, are required to prevent extrahepatic metastases.

To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer.