Hepatic arterial administration of activated leukocytes in patients with liver metastases.

BACKGROUND: Liver is the most common site of metastatic disease. Hepatic arterial infusion (HAI) of cytotoxic drugs may achieve high objective response rate. METHODS: Peripheral blood mononuclear cells were obtained by leukapheresis after stimulation with subcutaneous GM-CSF in six patients and with subcutaneous interleukin-2 (IL-2) in four patients, all with nonresectable hepatic metastases not responsive to conventional regimens. After the cytokine stimulation, the cells were administered by HAI either alone, or after HAI of melphalan (50 mg). RESULTS: Mean number of 23.1 +/- 4.6 x 10(9) and 19.0 +/- 9.7 x 10(9) mononuclear cells were obtained through leukapheresis after GM-CSF and IL-2 priming, respectively. Significant cytotoxic activity was observed only after short IL-2 stimulation. A marked decrease in tumor markers was observed in two patients treated by combination of melphalan and activated leukocytes. CONCLUSIONS: HAI is a technically feasible way of regional delivery of a high number of activated leukocytes obtained after short ex vivo activation.

Effect of irinotecan on the phenotype of peripheral blood leukocyte populations in patients with metastatic colorectal cancer.

BACKGROUND/AIMS: Previous studies have demonstrated a significant decrease in absolute numbers of CD3+CD4+, CD8+CD28+ and CD19+ lymphocytes, and an increase in the expression of activation markers on T-cells and the number of CD14+CD16+ monocytes in patients with metastatic cancer. Irinotecan (CPT-11) is now being widely used for treatment of metastatic colorectal cancer patients. METHODOLOGY: We have examined, by two-color flow cytometry, peripheral blood leukocyte populations before and during systemic treatment with CPT-11 in 14 patients with metastatic colorectal cancer. RESULTS: CD3+, CD3+CD4+, CD3+CD8+, CD8+CD28+ and CD19+ were significantly lower, and CD3+HLA-DR+ and CD14+CD16+ cells were higher in metastatic colorectal cancer patients compared to controls. After 2-4 months of CPT-11-based chemotherapy, significant increase in CD3+CD4+ cell numbers was observed in 8 patients who had initial CD3+CD4+ counts of less than 600 per microL (358 +/- 154 vs. 652 +/- 319 cells per microL, Wilcoxon test, P < 0.01), while in patients with higher initial CD3+CD4+ counts a trend for decrease was observed during therapy. A trend for an increase in CD8+CD28+ cell counts was observed in patients with low CD3+CD4+ numbers, but no other changes were observed during the treatment in other peripheral blood leukocyte populations examined. CONCLUSIONS: CD3+CD4+ lymphocytopenia, a decrease in CD8+CD28+ and CD19+ lymphocytes, increased expression of activation markers and CD14+CD16+ monocytosis are present in a significant proportion of metastatic colorectal cancer patients. CPT-11-based therapy seems to ameliorate CD3+CD4+ lymphocytopenia, possibly by neutralizing the immunosuppressive effects of uncontrolled tumor growth. These observations may be useful for the design of immunotherapy trials in metastatic colorectal cancer.

Regional chemotherapy in biliary tract cancers--a single institution experience.

BACKGROUND/AIMS: The prognosis of biliary tract cancers is poor. The aim of the present report was to analyze retrospectively the effectiveness of regional chemotherapy in patients with biliary tract cancers treated at a single institution. METHODOLOGY: Thirty-two patients with biliary tract cancers, 17 patients with cholangiocarcinoma and 15 patients with gallbladder carcinoma, were treated by regional administration of the chemotherapy, usually the combination of 5-fluorouracil, cisplatin and folinic acid. Eighteen patients with inoperable tumors received no surgical treatment, 10 patients were treated by palliative resection (cohort B), and 4 patients received radical surgery (cohort C). RESULTS: The median survival of the patients is (mean +/- standard deviation) 14 +/- 17+ (median 7+) months for cohort A patients, 22 +/- 17+ (median 17+) months for cohort B patients, and 32 +/- 4+ (median 33+) months for cohort C patients. One-year survival was 38% (6 out of 16 patients) for cohort A, 80% (8 out of 10 patients) for cohort B, and 100% (4 out of 4 patients for cohort C). Two-year survival was 15% (2 out of 13) for cohort A, 30% (3 out of 10) for cohort B, and 100% (4 out of 4) for cohort C. One out of 12 patients (8%) in cohort A and 1 out of 10 patients (10%) in cohort B survived more than 5 years. After intraarterial chemotherapy, a significant increase was observed in the absolute numbers of CD3+, CD3+CD8+ and CD8+CD28+ lymphocytes, as well as an increase in CD3+CD4+ and natural killer lymphocytes. CONCLUSIONS: Regional chemotherapy is active in controlling the disease, and seems to result in prolongation of survival in patients with biliary tract cancer. Administration of regional chemotherapy is also associated with a rise of circulating lymphocyte numbers.