Jindriska Mergancova

Pegylated Liposomal Doxorubicin in Combination with Hyperthermia for Treatment of Skin Metastases of Breast Carcinoma: A Case Report

Background: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. Case Report: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx®) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41–43 °C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. Conclusion: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.

HEPATIC ARTERIAL INFUSION CHEMOTHERAPY IN GASTRIC CANCER: A REPORT OF FOUR CASES AND ANALYSIS OF THE LITERATURE

Aims and background Gastric cancer is associated with high mortality. Although the liver is a common site of metastases in this tumor, the experience with liver-directed therapies is limited. Methods We report a single-center experience involving four patients with liver metastases from gastric cancer treated by hepatic arterial infusion (HAI). In addition, we performed a search for reports on HAI in gastric cancer metastatic to the liver and used the studies with data on survival of individual patients for a pooled analysis. Results Among three valuable patients, one had a complete response, one had stable disease and one had progressive disease. The patient with complete response is still alive 41 months after the diagnosis of liver metastases, while the other patients died 6, 22 and 31 months after the diagnosis. Objective responses were observed in 48% of the 25 patients in the pooled analysis. Objective response and limited hepatic involvement were independent predictors of survival in these patients. Conclusions Although isolated liver involvement in metastatic gastric cancer is rare, HAI seems to be similarly effective in these patients as in patients with liver metastases from colorectal cancer. The prognosis is significantly better in gastric cancer patients who have limited hepatic involvement and attain an objective response after HAI.

Pegylated liposomal doxorubicin in combination with hyperthermia in the treatment of a case of advanced hepatocellular carcinoma.

Background Currently, there is no standard treatment of inoperable advanced hepatocellular carcinoma. Study A patient with advanced hepatocellular carcinoma was treated with intravenous infusion of pegylated liposomal doxorubicin (PLD, Caelyx) in combination with ultrasound hyperthermia of the liver. Each cycle consisted of infusion of 60 mg of PLD followed by two fractions of hyperthermia 41°C to 43°C for 45 minutes 1 and 48 hours after infusion, respectively. Results A substantial regression of the tumor was observed on computed tomography scans. No toxicity of combined treatment was noted. Conclusions This may be the first report of the combination of PLD and hyperthermia in the treatment of advanced hepatocellular carcinoma. Our observation suggests that the combination of PLD with hyperthermia is technically feasible, well tolerated, and could have synergistic potential.

Systemic Immune Activation and Peripheral Blood Lymphocytes during Primary Chemotherapy with the Combination of Doxorubicin and Paclitaxel in Patients with Breast Carcinoma

Abstract In recent years, there has been interest in the study of alterations of the immune system of breast carcinoma patients undergoing primary chemotherapy. Changes in the phenotype, function of peripheral blood lymphocytes as well as alterations in the release of pro-inflammatory cytokines accompanying the administration of primary chemotherapy have been described. We have investigated urinary neopterin and peripheral blood leukocyte phenotype in 44 breast carcinoma patients treated with the combination of doxorubicin and paclitaxel. Compared to controls, patients with breast carcinoma had significantly lower relative number of CD3+ lymphocytes, and significantly higher relative and absolute numbers of natural killer cells, relative and absolute numbers of CD3+DR+ lymphocytes, relative and absolute numbers of CD3+CD69+ lymphocytes, relative numbers of CD8+CD57+ lymphocytes and CD14+DR+ monocytes and relative and absolute numbers of CD14+CD16+ monocytes. A significant correlation was observed before the initiation of therapy between urinary neopterin and the relative numbers of CD3+CD4+ lymphocytes (rs = - 0.411, p < 0.01), absolute numbers of CD3+CD4+ lymphocytes (rs = - 0.313, p < 0.05), relative number of CD3+CD8+ lymphocytes (rs = 0.352, p < 0.05), CD4+/CD8+ ratio (rs = -0.404, p < 0.01), relative numbers of CD3+DR+ lymphocytes (rs = 0.343, p < 0.05), absolute numbers of CD3+DR+ lymphocytes (rs = 0.306, p < 0.05), and relative numbers of CD8+CD57+ lymphocytes (rs = 0.410, p < 0.01). Urinary neopterin and peripheral blood leukocyte phenotype was followed in 44 breast carcinoma patients treated by primary chemotherapy with doxorubicin and paclitaxel before the start of the treatment and on 3 subsequent visits in approximately monthly intervals. Compared to pretreatment values, urinary neopterin, relative and absolute numbers of CD3+, CD3+CD4+ and CD8+CD28+ lymphocytes were significantly increased throughout the course of treatment. No significant changes were observed in relative and absolute numbers of NK cells, CD8+- CD57+, CD3+DR+, CD3+CD25+, and CD3+CD69+ lymphocytes. In contrast, the relative and absolute numbers of CD19+ lymphocytes and CD19+CD23+ lymphocytes were significantly decreased throughout the course of therapy. The relative and absolute numbers of monocytes were significantly increased throughout the course of therapy. Significantly increased absolute numbers were also observed for CD14+DR+ and CD14+CD16+ monocytes. Among 37 evaluable patients, pathological complete response of the primary tumor, including regional lymph nodes, was observed in 6 cases. In patients with pathological complete response relative and absolute numbers of lymphocytes and absolute numbers of CD4+ lymphocytes were significantly lower at baseline. A total of 18 patients had evidence of pathological involvement of the lymph nodes. Compared to patients with lymph node involvement detected in surgical specimen, 19 patients without lymph node involvement had at baseline significantly lower relative and absolute number of lymphocytes, absolute numbers of CD3+, CD3+CD4+, CD3+DR+ and CD8+CD57+ lymphocytes. When ratio of peripheral blood leukocyte counts at visit 2/visit 1 was calculated, patients without lymph node involvement at surgery also had significantly increased ratio of relative lymphocyte numbers, relative and absolute CD14+DR+ monocyte numbers. In conclusion, systemic immune activation in breast carcinoma patients treated with doxorubicin and paclitaxel is associated with significant changes of peripheral blood leukocyte phenotype, including an increase of relative and absolute numbers of CD3+CD4+ lymphocytes.

Concentrations of neopterin, kynurenine and tryptophan in wound secretions of patients with breast cancer and malignant melanoma: a pilot study

Abstract The aim of the present pilot study was to investigate the concentrations of neopterin, kynurenine and tryptophan in wound secretion in patients undergoing surgery for breast cancer or malignant melanoma. Twenty-two patients, 16 females and 6 males, undergoing surgery for breast cancer (n=15) or malignant melanoma (n=7) were evaluated. Neopterin, kynurenine and tryptophan were determined using a high-performance liquid chromatography method. When the concentrations in wound secretions from the primary breast tumor and the axilla were compared, the neopterin/tryptophan ratio was significantly higher in the tumor wound secretions (0.92±0.41 vs. 0.61±0.14 mmol/mol; p=0.049), but no significant differences were observed in neopterin (49.2±28.6 vs. 31.5±11.1 nmol/L), tryptophan (52.9±13.0 vs. 51.2±13.3 μmol/L) and kynurenine concentrations (5.97±7.49 vs. 5.34±6.25 μmol/L) and kynurenine/tryptophan ratio (108.1±107.7 vs. 103.5±106.7 mmol/mol). No marked differences were noted in neopterin, tryptophan and kynurenine concentrations and kynurenine/tryptophan and neopterin/tryptophan ratios in sequential samples from the axilla of breast cancer patients obtained on days 1 and 2. In conclusion, present data demonstrate that the measurement of neopterin, kynurenine and tryptophan can be used to monitor local immune response after cancer surgery.