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Biomedical subjects

P Lissoni

Publications and source records attributed to P Lissoni.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors.

Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in association with the pineal hormone MLT may constitute a new well-tolerated and potentially active therapy of untreatable advanced endocrine tumors.

Abdominal Neoplasms↗
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A randomized study of low-dose subcutaneous interleukin-2 plus melatonin versus supportive care alone in metastatic colorectal cancer patients progressing under 5-fluorouracil and folates.

Chemotherapy with 5-fluorouracil (5-FU) and folates represents the first-line standard therapy for metastatic colorectal cancer, whereas at present there is no conventional second-time treatment. Because of its importance in generating an effective anticancer immune response, interleukin-2 (IL-2) could constitute a new promising therapy of advanced colon cancer. Generally, IL-2 may determine tumor regressions in colon cancer only when it is given at high toxic doses. Our preliminary studies have shown that the pineal hormone melatonin may amplify IL-2 activity, which becomes active also at low doses in several tumor histotypes. On the basis, we have performed a clinical trial to evaluate the impact of low-dose IL-2 plus melatonin on the survival time in metastatic colon cancer, which progressed in response to 5-FU plus folates. The study included 50 metastatic colorectal cancer patients, who did not respond or progressed after initial response to first-line chemotherapy with 5-FU and folates. Patients were randomized to receive supportive care alone or low-dose subcutaneous IL-2 (3 million IU/day for 6 days/week for 4 weeks) plus melatonin (40 mg/day orally). No spontaneous tumor regression occurred in patients receiving supportive care alone. A partial response was achieved in 3/25 patients treated with immunotherapy. Percent survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with supportive care alone (9/25 vs. 3/25, p < 0.05). This study suggests that low-dose subcutaneous IL-2 plus melatonin may be effective as a second-line therapy to induce tumor regression and to prolong percent survival at 1 year in metastatic colorectal cancer patients progressing under 5-FU and folates.

Adult↗
PubMedDate not supplied

A biological study on the efficacy of low-dose subcutaneous interleukin-2 plus melatonin in the treatment of cancer-related thrombocytopenia.

The production of cytokines involved in platelet generation, including interleukin (IL)-3, IL-6 and IL-11, is stimulated by IL-2. However, the platelet number has been shown to decrease on IL-2 cancer therapy, and this side effect depends on the enhanced peripheral platelet destruction following the activation of the macrophage system by IL-2 itself. Our previous studies showed that IL-2-induced macrophage activation may be counteracted by the pineal hormone melatonin (MLT). On this basis, a pilot study with IL-2 plus MLT was performed to evaluate its influence on the platelet number in cancer patients with persistent thrombocytopenia. The study included 20 advanced solid tumor patients, who received IL-2 at 3 million IU/day s.c. for 6 days/week for 4 weeks in association with MLT (40 mg/day orally). A normalization of the platelet number was achieved in 14/20 (70%) patients. This pilot study shows that the therapy with low-dose IL-2 plus MLT, in addition to its previously described antitumor activity, may also be effective in the treatment of cancer-related thrombocytopenia.

Adult↗
PubMedDate not supplied

Prediction of recurrence in operable breast cancer by postoperative changes in prolactin secretion.

It has been demonstrated that breast surgery may induce prolactin (PRL) increase. Because of the potential stimulatory role of PRL on breast cancer cells, its postoperative increase may influence the prognosis of breast cancer patients. This study was performed to evaluate the influence of surgery-induced hyperprolactinemia on recurrence rate in operable breast cancer. The study included 250 consecutive breast cancer patients, clinical stage T1-3 N0-2M0, who were observed for a median follow-up of 72 months. Surgery-induced hyperprolactinemia occurred in 108/250 patients (43%). Irrespectively of node involvement, hormonal receptor, type of surgery and adjuvant therapies, the relapse rate was significantly higher in patients who had no surgery-induced hyperprolactinemia than in those with postoperative PRL increase (64/142 vs. 23/108; p < 0.001). This difference was also significant in relation to node status (N0:22/63 vs. 5/56, p < 0.001; N+:42/79 vs. 18/52, p < 0.05). The present study shows that a surgery-induced rise of PRL, despite its potential stimulation of cancer cell growth, is paradoxically associated with a longer disease-free survival in operable breast carcinoma in both patients with or without axillary node involvement. Moreover, this study suggests that the prognosis of node-negative patients who did not show postoperative hyperprolactinemia tends to be similar to that of patients with node involvement and surgery-induced PRL enhancement. Therefore, the lack of surgery-induced hyperprolactinemia would have to be grouped together with the unfavorable prognostic factors of breast cancer.

Adult↗
PubMedDate not supplied

Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone.

The prognosis of brain glioblastoma is still very poor and the median survival time is generally less than 6 months. At present, no chemotherapy has appeared to influence its prognosis. On the other hand, recent advances in brain tumor biology have suggested that brain tumor growth is at least in part under a neuroendocrine control, mainly realized by opioid peptides and pineal substances. On this basis, we evaluated the influence of a concomitant administration of the pineal hormone melatonin (MLT) in patients with glioblastoma treated with radical or adjuvant radiotherapy (RT). The study included 30 patients with glioblastoma, who were randomized to receive RT alone (60 Gy) or RT plus MLT (20 mg/daily orally) until disease progression. Both the survival curve and the percent of survival at 1 year were significantly higher in patients treated with RT plus MLT than in those receiving RT alone (6/14 vs. 1/16). Moreover, RT or steroid therapy-related toxicities were lower in patients concomitantly treated with MLT. This preliminary study suggests that a radioneuroendocrine approach with RT plus the pineal hormone MLT may prolong the survival time and improve the quality of life of patients affected by glioblastoma.

Adult↗
PubMedDate not supplied

Preoperative interleukin-2 subcutaneous immunotherapy may prolong the survival time in advanced colorectal cancer patients.

It has been demonstrated that surgery may induce immunosuppression. This finding could influence the clinical course of surgically treated cancer patients. Moreover, preliminary experimental studies have shown that a preoperative injection of IL-2, whose importance in generating the antitumor immune response is well known, may neutralize surgery-induced immunosuppression. At present, however, it is still unknown whether preoperative IL-2-induced immune improvement in the postoperative period may influence the prognosis of surgically treated cancer patients. The present study was performed to evaluate the prognostic impact of IL-2 presurgical therapy in advanced colorectal cancer patients. The study included 50 colorectal cancer patients, Dukes' stage D, who were randomized to be treated with or without IL-2 preoperatively (18.10(6) IU/day subcutaneously for 3 consecutive days). After surgery, all patients underwent chemotherapy with 5-FU and folates until disease progression. Postoperative mean numbers of lymphocytes, T lymphocytes, natural killer cells and activated lymphocytes were significantly higher in IL-2-treated patients than in controls. Moreover, the percent of lymphocytic and/or eosinophilic tumor infiltration was significantly higher in IL-2 group than in controls. Finally, both survival curve and the percent of survival at 1 year were significantly greater in patients pretreated with IL-2 than in controls. This clinical trial demonstrates that preoperative IL-2-induced neutralization of postoperative lymphocytopenia is associated with a prolonged survival time in advanced colorectal cancer patients.

Adult↗
PubMedDate not supplied

Second-line therapy with interferon-alpha plus vinblastine in metastatic renal cell cancer patients progressed under interleukin-2 subcutaneous immunotherapy.

AIMS AND BACKGROUND: Interferon (IFN) +/- vinblastine (VNB) has appeared to be effective as first-line therapy of metastatic renal cell cancer. This study was performed to establish the efficacy of IFN plus VNB in metastatic RCC previously treated with interleukin-2 (IL-2). METHODS: The study included 14 metastatic renal cell cancer patients who did not respond to IL-2 subcutaneous therapy or who relapsed after initial response or stable disease. IFN-alpha 2a was given subcutaneously at 3 million U thrice a week in association with VNB (0.1 mg/kg i.v. every 21 days) until progression or toxicity. Patients were considered as evaluable when they were treated for at least 1 month. RESULTS: Evaluable patients were 13/14. No patient had a complete response. Partial response was achieved in 2/13 (15%) patients. Stable disease was seen in 5/13 patients, and the last 6 progressed. CONCLUSIONS: This study, by showing a tumor response rate comparable to that reported with first-line therapy, suggests that previous IL-2 immunotherapy does not influence negatively the efficacy of IFN+VNB in metastatic renal cell cancer.

Aged↗
PubMedDate not supplied

Clinical efficacy of cancer subcutaneous immunotherapy with interleukin-2 in relation to the pretreatment levels of tumor growth factor insulin-like growth factor-1.

AIMS AND BACKGROUND: IGF-1 has been proven to be one of the most important growth factors for normal and neoplastic cells. Abnormally high levels of IGF-1 have been observed in cancer patients. Since it has been demonstrated that some growth factors may counteract the action of antitumor cytokines, the presence of increased IGF-1 concentrations could reduce the efficacy of cancer biotherapies with cytokines, such as IL-2. The present study was performed to evaluate the efficacy of IL-2 immunotherapy in relation to the pretreatment levels of IGF-1 in advanced cancer patients. METHODS: The study included 20 consecutive patients with metastatic renal cell cancer who were treated subcutaneously with IL-2 at 6 million IU/day for 5 days/week for 6 weeks. IGF-1 serum levels were measured by RIA on venous blood samples collected before the immunotherapy, after 3 weeks, and at the end of IL-2 injection. RESULTS: Objective tumor regressions were obtained in 5/20 patients, consisting of 1 complete response (CR) and 4 partial responses (PR). Nine patients had stable disease and the last 6 patients progressed. Abnormally high pretreatment levels of IGF-1 were seen in 13/20 patients. The percent of clinical responses (CR + PR) was significantly higher in patients with normal pretreatment concentrations of IGF-1 than in those with elevated levels (4/7 vs 1/13, P < 0.01). No significant changes in mean IGF-1 levels occurred during IL-2 therapy. However, mean IGF-1 levels increased in progressing patients and decreased in those with a response or stable disease, even though none of the differences was statistically significant. CONCLUSIONS: The study showed that high pretreatment levels of IGF-1 are associated with a reduced efficacy of IL-2 immunotherapy of renal cancer. Further studies are required to establish whether IGF-1 levels simply reflect the extension of disease, or whether they may influence per se the action of IL-2.

Analysis of Variance↗
PubMedDate not supplied

Endocrine effects of granulocyte colony-stimulating factor in cancer patients.

AIMS AND BACKGROUND: In addition to well-documented endocrine properties of interleukins, hemopoietic growth factors could also exert hormonal activities. In fact, our previous studies have shown that GM-CSF may stimulate cortisol and GH release. In contrast, few data only are available about the possible effects of G-CSF. This study was carried out to investigate endocrine effects of G-CSF in cancer patients. METHODS: The study included 8 cancer patients who were investigated after G-CSF (0.3 mg subcutaneously) or during saline infusion alone as control by collecting venous samples at zero time and after 2, 4, 6 and 8 h. Serum levels of cortisol, GH, PRL, FSH. LH, TSH and melatonin were measured by the RIA method. RESULTS: The circadian rhythm of cortisol was not influenced by G-CSF. No significant differences in mean levels of GH, PRL, FSH or LH were seen after G-CSF and during saline infusion. Both TSH and melatonin decreased after G-CSF, without, however, significant differences with respect to the values seen on saline alone. CONCLUSIONS: The study showed that G-CSF has no substantial endocrine affects in humans. Therefore, G-CSF would differ from GM-CSF not only for its hemopoietic properties, but also from an endocrine point of view.

Granulocyte Colony-Stimulating Factor↗
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Effects of one-year adjuvant treatment with tamoxifen on bone mineral density in postmenopausal breast cancer women.

In this study, the authors have analyzed the possible effects of one-year adjuvant treatment with tamoxifen on bone mineral density in postmenopausal breast cancer women. Bone mineral content was studied by photon absorptiometry (I-125), whereas bone balance was analyzed indirectly by serum PTH, osteocalcin, calcitonin, calcium and alkaline phosphatase levels. Bone mineral content and serum bone-related substances were measured before starting treatment and after one year. Results were analyzed using Student's t test for paired data. No difference was found between the two measurements for bone mineral content, PTH, calcitonin, calcium and alkaline phosphatase levels. Measurements at entry and after one year of treatment showed a statistically significant difference (P<0.001) only for osteocalcin. In accordance with other authors, we can conclude that treatment with tamoxifen does not cause an increase in menopausal bone resorption. The finding that osteocalcin levels decreased after one year of therapy with tamoxifen is interesting, but further studies are necessary to clarify the role of such levels in predicting a turnover of bone balance towards osteoblastic activity.

Adult↗
PubMedDate not supplied

Characterization of cancer-related disseminated intravascular coagulation in relation to tumor necrosis factor-alpha blood concentrations: possible therapeutic role of pentoxifylline.

AIMS AND BACKGROUND: Preliminary experimental data suggest the involvement of tumor necrosis factor (TNF) in determining endothelial damage related to disseminated intravascular coagulation (DIC). The present study was performed to investigate TNF secretion in DIC occurring in metastatic solid tumor patients and to evaluate the possible therapeutic role of pentoxifylline, which has been proven to have a TNF-lowering activity. METHODS: The study included 20 metastatic solid tumor patients who showed clinical and laboratory signs of DIC. Pentoxifylline was given orally at a dose of 1200 mg/day for 28 days. RESULTS: Abnormally high levels of TNF were found in 13/20 patients, and mean TNF serum levels observed in patients were significantly higher than those seen in a control group of 50 healthy subjects. Fibrinogen plasma concentrations were low in 11 cases. Patients with low fibrinogen values showed significantly higher mean TNF levels than those with normal or elevated concentrations. Pentoxifylline therapy induced a significant decrease in mean TNF concentrations and a significant increase in mean platelet number, which returned to within the normal range in 11/20 patients. An increase in platelets in response to pentoxifylline was more evident in patients with elevated pretreatment TNF values. CONCLUSIONS: Our results suggest the existence of abnormally high blood levels of TNF in cancer-related DIC, mainly in the presence of low fibrinogen values. Moreover, they indicate that pentoxifylline therapy may determine a decrease in TNF levels in DIC patients, an event associated with an increase in platelet number.

Adult↗
PubMedDate not supplied

Clinical efficacy of the aromatase inhibitor anastrozole in relation to prolactin secretion in heavily pretreated metastatic breast cancer.

AIMS AND BACKGROUND: It is known that the aromatase inhibitors may act by decreasing estrogen levels. Moreover, it is known that estrogens may stimulate the release of prolactin (PRL), which is a growth factor for breast cancer. This phase II study was performed to evaluate the effects of the novel aromatase inhibitor anastrozole on PRL secretion in metastatic breast cancer and the possible influence of PRL pretreatment levels on the efficacy of therapy. METHODS: The study involved 14 pretreated metastatic breast cancer patients with a poor clinical status. Anastrozole was given orally once a day at 1 mg/day for at least 2 months. To evaluate PRL secretion, venous blood samples were collected before treatment and at 1-monthly intervals during treatment. RESULTS: The clinical response consisted of partial response (PR) in 2, stable disease (SD) in 5 and progressive disease (PD) in the remaining 7 patients. Abnormally high pretreatment levels of PRL were seen in 5/14 (36%) patients. Progressing patients showed significantly higher pretreatment levels of PRL than those who achieved PR or SD. None of the patients with high PRL pretreatment levels showed a decline in PRL levels on treatment with anastrozole. CONCLUSIONS: This preliminary study suggests that anastrozole has no inhibitory effect on PRL secretion in metastatic breast cancer and that the evidence of abnormally elevated concentrations of PRL prior to therapy is generally associated with a lack of efficacy.

Administration, Oral↗
PubMedDate not supplied

Endocrinological study of the dopaminergic regulation of prolactin release in metastatic breast cancer.

AIMS AND BACKGROUND: Prolactin (PRL) may be a growth factor for breast cancer. Abnormally high levels of PRL have been proven to be associated with a poor prognosis in metastatic breast cancer. However, most studies have been limited to the evaluation of basal levels of PRL rather than its response to the classical endocrine dynamic tests. This study was performed to analyse the dynamic secretion of PRL under stimulatory and inhibitory tests in metastatic breast cancer. METHODS: The study included 10 untreated metastatic breast cancer women, who were evaluated after the classical stimulatory and inhibitory tests for PRL secretion with the antidopaminergic agent Metoclopramide (10 mg iv as a bolus) and with L-dopa, respectively. Serum levels of PRL were measured by RIA before and at subsequent intervals after drug administration. PRL levels were considered to be elevated when they were higher than 25 ng/ml. RESULTS: Abnormally high basal levels of PRL were seen in 6/10 patients. L-dopa was unable to inhibit PRL secretion, whose mean concentrations paradoxically significantly increased in response to L-dopa, with values comparable to those observed after the classical stimulatory test with metoclopramide. CONCLUSIONS: This study confirm the existence of hyperprolactinemia associated with metastatic breast cancer. In addition, by showing a paradoxical rise of PRL in response to L-dopa, which inhibits PRL secretion in physiological conditions, this study would suggest that breast cancer-related hyperprolactinemia may depend at least in part on endogenous disease-related neuroendocrine alterations.

Adult↗
PubMedDate not supplied

Circulating immature and mature dendritic cells in relation to lymphocyte subsets in patients with gastrointestinal tract cancer.

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.

Antigens, CD↗
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Changes in circulating dendritic cells and IL-12 in relation to the angiogenic factor VEGF during IL-2 immunotherapy of metastatic renal cell cancer.

Angiogenesis and immunosuppression are the main biological mechanisms responsible for cancer progression. Moreover, recent observations suggesting a negative influence of angiogenesis on anticancer immunity have shown that some angiogenic factors, such as VEGF, may induce immunosuppression. In addition, the evidence of abnormally high blood levels of VEGF has been proven to be associated with resistance to IL-2 immunotherapy. The present study was performed to establish a possible relation ship between the efficacy of IL-2 cancer immunotherapy and changes in circulating levels of VEGF, IL-12, mature and immature dendritic cells (DC). The study included 25 metastatic renal cell cancer patients who underwent subcutaneous low-dose IL-2 immunotherapy (6 MIU/day for 6 days/week for 4 weeks). Immature and mature DCs were identified as CD123+ and CD11c+ cells, respectively. The clinical response consisted of partial response (PR) in five, stable disease (SD) in 11 and progressive disease (PD) in the remaining nine patients. The mean IL-12 levels observed during IL-2 immunotherapy were significantly higher in patients with PR or SD than in those with PD, whereas the mean VEGF concentrations were significantly higher in patients who had PD than in those with PR or SD. Finally, a significant increase in the mean number of circulating mature DCs occurred only in patients with PR or SD, whereas no significant change was seen in patients with PD. By contrast, no significant change was observed in the mean number of immature DCs. This study shows that the efficacy of IL-2 immunotherapy is associated with a significant increase in circulating mature DCs and IL-12, without any concomitant increase in VEGF concentrations. Further studies will be required to better define the relationship between activation of anticancer immunity and control of angiogenesis-related mechanisms.

Adult↗
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Chemotherapy and angiogenesis in advanced cancer: vascular endothelial growth factor (VEGF) decline as predictor of disease control during taxol therapy in metastatic breast cancer.

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.

Aged↗