Thrombocytopenia is a frequent complication of cancer and constitutes an absolute contraindication for chemotherapy. Recent studies have demonstrated that platelet generation may be influenced by both cytokines and neurohormones. In particular, the pineal indole melatonin has been proven to enhance platelet number in patients with thrombocytopenia due to different reasons. On this basis, we have evaluated the effects of a concomitant administration of melatonin in thrombocytopenic cancer patients undergoing chemotherapy. The study was performed in 14 metastatic breast cancer women treated by weekly epirubicin. Each cycle consisted of epirubicin at 25 mg/m2 i.v. at weekly intervals. Melatonin was given orally at 20 mg/day in the evening every day, starting 7 days prior to chemotherapy. Patients were considered as evaluable when they received at least four cycles of chemotherapy. Evaluable patients were 12/14. The induction phase with melatonin induced a normalization of platelet number in 9/12 evaluable patients, and no further platelet decline occurred in chemotherapy. Objective tumor regression was achieved in 5/12 (41%) patients. This preliminary study would suggest that melatonin may be effective in the treatment of cancer-related thrombocytopenia and to prevent chemotherapy-induced platelet decline. Until now, melatonin therapy of cancer has been generally considered as an alternative treatment to chemotherapy. In contrast, this study would suggest that melatonin may contribute to the realization of chemotherapy in metastatic cancer patients unable to tolerate the chemotherapeutic approach because of persistent thrombocytopenia.
Angiogenesis is essential for tumor growth. Since vascular endothelial growth factor (VEGF) represents the main angiogenic factor, the control of VEGF secretion could constitute the most important mechanism to achieve the inhibition of angiogenesis-related processes. High blood concentrations have been proven to correlate with poor prognosis in advanced cancer. In experimental conditions, chemotherapeutic agents such as taxol appeared to inhibit VEGF-induced angiogenesis, while at present there are no data about the influence of chemotherapy on VEGF secretion in cancer patients. This preliminary study was performed to evaluate the effect of taxol therapy on VEGF secretion in advanced cancer patients in relation to the clinical response. The study included 14 patients with metastatic breast cancer who were treated with taxol monochemotherapy (175 mg/m2 i.v. every 21 days for three cycles). Serum levels of VEGF were measured by ELISA in blood samples collected before therapy and at 21-day intervals. The clinical response consisted of partial response (PR) in three and stable disease (SD) in six patients, whereas the other five patients had progressive disease (PD). Abnormally high pre-treatment levels of VEGF were seen in 8/14 patients. VEGF mean values significantly decreased during taxol therapy in patients with PR or SD, whereas no decline was observed in patients with PD. Moreover, the percent of normalization or decline greater than 50% in VEGF levels was significantly higher in patients with PR or SD than in those with PD (5/9 vs. 0/5). This preliminary study would suggest that the efficacy of taxol therapy in metastatic breast cancer - at least in terms of disease stabilization - may be associated with a decrease in VEGF blood levels followed by potential inhibition of cancer-related neovascularization.
Abnormally high blood levels of vascular endothelial growth factor (VEGF) appear to be associated with a poor prognosis in advanced cancer, probably as a consequence of its angiogenic and immunosuppressive effects. The prognostic significance of changes in VEGF secretion during cancer chemotherapy is still unknown. This study aimed to investigate the relation between VEGF variations and therapeutic results during chemotherapy in advanced malignancies. The study included 90 metastatic cancer patients, 59 with non-small cell lung cancer and 31 with colorectal carcinoma. Chemotherapy consisted of cisplatin plus etoposide for NSCLC and camptothecin for colorectal cancer. Abnormally high (> 2 SD with respect to values in healthy controls) pretreatment VEGF levels were found in 38/90 (42%) patients. The percentage of non-progressive disease in response to chemotherapy was significantly higher in patients with normal levels of VEGF prior to therapy than in those with elevated pretreatment values of VEGF (10/32 vs 4/27; p < 0.05). Moreover, the percentage of VEGF level normalization during chemotherapy was significantly higher in patients with objective tumor response or stable disease than in progressing patients (10/18 vs 0/20; p < 0.001). Finally, among patients with tumor response or disease stabilization, the one-year survival rate was significantly higher in patients with chemotherapy-induced normalization of VEGF than in those with persistently high VEGF blood levels (9/10 vs 3/8; p < 0.05). These results suggest that changes in VEGF levels during chemotherapy may represent a useful biomarker to predict the effect of chemotherapy in terms of tumor response and survival in patients with metastatic solid neoplasms.
Cancer-related deficiency in circulating dendritic cells (DC), whose important anticancer role is well established, has been proven to be associated with lymphocytopenia. This study was performed to evaluate which lymphocyte subset is most markedly related to the failure of the DC system. The study included 30 patients with gastrointestinal tract cancer, 10 of whom had distant organ metastases. Immature and mature DCs were measured by FACS and monoclonal antibodies against CD123 and CD11c antigens, respectively. Low levels of immature and mature DCs were observed in 63% and 43% of patients, respectively. Patients with low levels of circulating mature DCs had significantly lower values of T lymphocytes, T helper lymphocytes and NK cells than those with normal mature DC levels. In contrast, no significant difference was seen between patients with normal or abnormally low values of immature DCs. Conversely, patients with a decreased number of T lymphocytes, T helper lymphocytes and NK cells showed significantly lower values of circulating mature DCs than those with lymphocyte subsets within the normal range, whereas no difference was seen in immature DC amounts. This study suggests that only mature DC deficiency may be associated with important lymphocyte subset alterations in cancer patients, whereas deficiency in immature DCs does not seem to be related to other immune cell disorders.
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