Petra Holečková

Urinary Neopterin in Patients with Metastatic Colon Cancer Treated with Patupilone

Abstract Despite increased efficacy of regimens combining cytotoxic drugs and targeted agents, most patients with metastatic colorectal cancer will ultimately die of the disease. Only a limited number of drugs have reproducible activity in therapy of this tumor, and new active agents are urgently needed. Promising results in the therapy of metastatic colorectal cancer have been reported for patupilone, an epothilone analogue. Similarly to taxanes, the cytotoxic mechanism of epothilones involves the stabilization of microtubules. Increased serum or urinary concentrations of neopterin have been described in patients with tumors of different primary locations, including colorectal cancer. Neopterin concentrations were reported to increase during the administration of cytotoxic agents, including taxane-based chemotherapy. We have studied serum neopterin in patients with colorectal cancer before and during the therapy with patupilone. Urinary neopterin/creatinine concentrations were determined with highperformance liquid chromatography. Increased urinary neopterin concentrations were observed at baseline in the majority of the patients. In most patients, neopterin concentrations further increased during the therapy, and a significant increase of urinary neopterin was observed in patients with normal baseline neopterin concentrations. A trend of decreased survival was observed for patients with high initial neopterin concentration. In conclusion, urinary neopterin is increased in colorectal cancer patients presenting for second or higher line of treatment. An increase of urinary neopterin during patupilone therapy suggests an activation of immune response by this agent.

Urinary Neopterin, Serum Retinol, α-tocopherol and Homocysteine in Breast Cancer Patients During Treatment with Bevacizumab and Chemotherapy

Abstract Bevacizumab, monoclonal antibody targeting vascular endothelial growth factor, is effective in different tumors, including colorectal carcinoma, non-small cell lung cancer, renal cell carcinoma and breast cancer. Increased serum or urinary concentrations of neopterin, an indicator of systemic immune response, have been described in patients with tumors of different primary locations, and further increase has been observed during anticancer therapy. An increase of urinary neopterin has been described after administration of cytokines, cytotoxic chemotherapy, or external beam radiation, but less is known about the effects of targeted agents on systemic immune response. We have studied serum homocysteine, C-reactive protein, α-tocopherol and retinol, and urinary neopterin in patients with metastatic breast cancer treated with bevacizumab, taxane and carboplatin. Homocysteine and C-reactive protein were determined immunochemically. α-tocopherol, retinol and urinary neopterin were determined by high performance liquid chromatography. Homocysteine, C-reactive protein and urinary neopterin decreased, while retinol and α-tocopherol increased during the therapy. In conclusion, the treatment of patients with metastatic breast cancer with bevacizumab, taxane and carboplatin resulted in the suppression of systemic inflammatory and immune response. The suppression of systemic inflammatory and immune response was associated with an increase in serum vitamin concentrations.

Serum Uric Acid and C-reactive Protein in Patients with Metastatic Colorectal Carcinoma During Combination Therapy with High-dose Folinic Acid

Abstract New spectrum of side effects has emerged with the introduction of targeted therapies, including changes in parameters determining cardiovascular risk. Among other laboratory parameters, hyperuricemia and elevated Creactive protein (CRP) are associated with increased risk of cardiovascular disease. The aim of the present study was to investigate the changes of serum uric acid and CRP during the therapy with cetuximab, combined with 5- fluorouracil and high-dose folinic acid, in patients with metastatic colorectal carcinoma and the association of these changes with the outcome of the therapy. CRP and uric acid were determined using particle-enhanced immunoturbidimetric assay and uricase method, respectively. Measurements before and during the treatment were compared by Wilcoxon signed rank test, and comparison between survivors and non-survivors was performed by Mann-Whitney U test. Compared to baseline (pre-treatment) concentrations, serum uric acid was decreased significantly throughout the course of the combination treatment with irinotecan, 5-fluorouracil, highdose folinic acid and cetuximab. The decrease was evident early in the course of treatment. Serum CRP was also decreased significantly throughout the most of the course of therapy. The significant decrease of serum uric acid and CRP was evident already one week after the start of treatment. Serum CRP was significantly lower in patients who survived 12 months, but no difference of uric acid concentrations between survivors and non-survivors was found. A marked decrease of serum uric acid was observed during the combination therapy. High CRP was associated with poor prognosis, but no association between uric acid and prognosis was noted.