Regulation of neurotrophic functions: proteinase inhibitors.
Explore the source record for details and available documents.
Agrin↗
Biomedical subjects
L Fumagalli
Publications and source records attributed to L Fumagalli.
Which immunological parameters are clinically essential to monitor IL-2 cancer immunotherapy?
The evaluation of the immunobiological changes occuring during IL-2 cancer immunotherapy is not only important to correlate them with the clinical response or to understand the immune mechanism involved in tumor growth control, but also to predict the efficacy of treatment itself. As far as the immune status of patients prior to therapy is concerned, the evidence of the activation of the inflammatory response correlates with resistance to IL-2. Therefore, the evidence of abnormally high pretreatment values of inflammatory response markers, including ESR, CRP, neopterin and SIL-2R, may predict a lack of IL-2 efficacy. In contrast, changes in inflammatory parameters during IL-2 administration have no prognostic significance. The evidence of elevated pretreatment levels of the immunosuppressive cytokine IL-10 has also an unfavourable prognostic significance. At the other side, the evidence of a marked increase in hemopoietic cells involved in tumor cell destruction, such as lymphocytes and eosinophils, as well as in blood levels of antitumor cytokines, such as IL-12, correlates with efficacy of IL-2 cancer immunotherapy. A better definition of the prognostic significance of immunoinflammatory markers will allow us to manipulate and improve host biological response during cancer immunotherapy with IL-2.
Blood Sedimentation↗
Circulating dendritic cells in early and advanced cancer patients: diminished percent in the metastatic disease.
Despite the well demonstrated fundamental role of dendritic cells (DC) in generating antitumor immunity in experimental conditions, to date there are only few preliminary studies which investigate the percent of DC in the peripheral blood of cancer patients. Several cell surface markers have now been described which are specific to cultured DC, however their expression in vivo is still controversial. Recently, however, two DC subsets, consisting of immature and mature DC, have been shown to be present in peripheral blood, which can be recognized as CD123+ and CD11c+ cells, respectively. On this basis, we decided to investigate the presence of both mature and immature DC in the peripheral blood of early or advanced cancer patients. The study included 40 solid tumor patients, 18 of whom had a locally limited disease, while the other 22 showed distant organ metastases. CD123+ and CD11c+ cells were detected by FACS using monoclonal antibodies, and expressed as the percent of total leukocytes. The control group consisted of 50 healthy subjects. The mean percent of both CD123+ and CD11c+ cells was significantly lower in cancer patients than in controls. Moreover, the mean percent of both DC subsets was significantly lower in metastatic patients than in the non-metastatic ones. This study, demonstrating significantly lower percents of both immature and mature DC in the peripheral blood of cancer patients, particularly in those with distant organ metastases, suggests that DC deficiency may play a role in inducing cancer-related immunosuppression. Therefore, the demonstration of a diminished percent of DC in peripheral blood may represent a new interesting biological marker predicting a poor prognosis in human neoplasms, as with lymphocytopenia, the unfavourable prognostic significance of which has been well demonstrated.
Adult↗
Ex-vivo purging of circulating monocytes results in immunovirologic improvement in partially HAART responder HIV-infected patients.
AIDS pathogenesis results from a complex array of immune alterations which include, among others, changes in the pattern of cytokine production. Some monocyte-derived cytokines, like TNFalpha play a major role in HIV pathogenesis. TNFalpha transactivates HIV NF-kB thereby inducing viral replication, potentiates HIV replication in lymphomonocytes TNFalpha is one of the main factors of HIV-induced cachexia and might be involved in HAART-associated lipodystrophy. In addition, monocytes are infectable by HIV in vitro and infected monocytes can be recovered from the blood of HIV infected patients. For these reasons, we tested whether renewal of the pool of circulating monocytes by selective monocyte apheresis may improve the immune reconstitution which follows treatment with highly active anti-retrovirals (HAART). HIV-infected HAART receiving (> 1 year) patients who were either virologically non-responders (HIV-1 RNA >50,000 copies/ml) or immunologically non-responders (CD4 counts < 200) were treated with a novel monocyte apheresis device (G-1 Adacolumn). Plasma HIV viral load, proviral DNA and phenotypic and functional immunological analyses were performed. G-1 apheresis was well tolerated, not accompanied by adverse responses, and followed by clinical improvement. TNFalpha production was suppressed and CD4 T cell counts increased. In one G-1 patient with elevated HIV-1 proviral DNA a significant reduction (from 1,500 to 40 copies/10(5) cells) was observed. Neither immunologic nor virologic parameters were modified in the control patients who received HAART alone. Thus, purging of circulating monocytes by G-1 apheresis has a dramatic suppressive effect on TNFalpha production and is followed by both clinical and immunovirological improvement. G-1 apheresis should be considered in patients in whom HAART is only partially effective.
Anti-HIV Agents↗
A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the pineal hormone melatonin in untreatable advanced hematologic malignancies.
Interleukin-2 (IL-2) has proven to be able to generate an effective anticancer immunity against both solid and hematologic malignancies. Moreover, recent advances in the knowledge of psychoneuroimmunology have demonstrated that anticancer immunity is under neuroendocrine control and that the pineal hormone melatonin (MLT) may stimulate the IL-2-dependent anticancer reaction. Finally, preliminary clinical studies have already shown that the concommitant administration of MLT may amplify the efficacy of IL-2 in the treatment of advanced solid neoplasms, whereas there are no data about MLT influence on IL-2 activity in hematologic malignancies. The aim of the present study was to evaluate the efficacy and tolerability of a neuroimmunotherapeutic combination of low-dose IL-2 plus MLT in advanced hematologic malignancies which did not respond to previous standard therapies. The study included 12 evaluable patients. Tumor histotypes were as follows: non-Hodgkin's lymphoma (NHL) 6; Hodgkin's disease (HD), 2; multiple myeloma, 2; acute myelogenous leukemia (ALM), 1 and chronic myelomonocytic leukemia (CMML), 1. IL-2 was injected subcutaneously at a dose of 3 million IU/day for 6 days per week for 4 weeks, corresponding to one cycle. MLT was given orally at 20 mg/day in the evening, without interruption. In non-progressing patients, a second IL-2 cycle was planned after a 3 week-rest period. A partial response was achieved in one patient with multiple myeloma. Stable disease occurred in 7 other patients (NHL, 3; HD, 1; AML, 1; CLLM, 1; multiple myeloma, 1), whereas the other 4 patients progressed. Therefore, lack of progression was obtained in 8 out of 12 (67%) patients, with a median duration of 21+ months (14-30+ months). The treatment was well tolerated in all patients. These preliminary results would suggest that the concomitant administration of low-dose IL-2 plus the pineal hormone MLT may prolong the survival time in untreatable advanced hematologic malignancies, with results comparable to those previously reported using a more toxic immunotherapy, consisting of high-dose IL-2 alone.
Adolescent↗
Abrogation of surgery-induced decline in circulating dendritic cells by subcutaneous preoperative administration of IL-2 in operable cancer patients.
Surgery-induced immunosuppression is characterized by a decline in lymphocyte count, particularly T lymphocyte number. In addition, preliminary studies have shown that the postoperative period is also characterized by a decline in the number of circulating dendritic cells (DC), whose fundamental anticancer role has been recently demonstrated. Previous studies had already shown that the preoperative injection of IL-2 may completely abrogate surgery-induced lymphocytopenia, whereas its eventual influence on DC system during the perioperative period is still unknown. The present study was performed to evaluate the influence of IL-2 preoperative immunotherapy on the perioperative changes in circulating DC number in patients affected by colorectal cancer. The study included 14 consecutive patients, who were randomized to be treated with or without IL-2 presurgical immunotherapy (12 million IU/day for 3 days subcutaneously). Circulating immature and mature cells were evaluated before surgery and at days 3 and 7 of the postoperative period. The detection was made by FACS using monoclonal antibodies against CD123 and CD11c to recognize immature and mature DC, respectively. Surgery induced a significant decline in the mean number of both immature and mature DC. The pre-surgical administration of IL-2 completely abrogated surgery-induced decline in immature DC cell amount. Moreover, mature DC mean number was diminished only at day 3 of the postoperative period, since the value observed at day 7 was not significantly lower than that found before surgery. This preliminary study shows that surgery-induced immunosuppression is characterized also by a significant decline in the mean number of both immature and mature DC. Moreover, this study would suggest that the preoperative immunotherapy with IL-2 may counteract surgery-induced failure of DC system. Because of the fundamental antitumor role of DC, this evidence could have a prognostic impact on the clinical course of the neoplastic disease.
Aged↗
Surgery-induced decline in circulating dendritic cells in operable cancer patients: a possible explanation of postoperative immunosuppression.
BACKGROUND/AIMS: The recent advances in the immunobiology of tumor have demonstrated the essential role of dendritic cells in anticancer immunity. Dendritic cells activate anticancer immunity by secreting interleukin-12 and by activating T helper lymphocytes, with the following production of interleukin-2. Since surgery-induced immunosuppression has been proven to be associated with a decline in the blood levels of both interleukin-2 and interleukin-12, it could depend at least in part on a transient deficiency of dendritic cells system. Unfortunately, at present there are no data about changes in circulating dendritic cell number during the postoperative period. This preliminary study was performed to evaluate the influence of surgery on dendritic cell number in the peripheral blood. METHODOLOGY: The study included 14 consecutive operable gastrointestinal tract cancer patients, who were evaluated before and at day 7 of the postoperative period. The control group consisted of 50 healthy subjects. Immature (CD 123+) and mature (CD 11+) dendritic cell subsets were measured by FACS and monoclonal antibodies. RESULTS: Cancer patients showed a significantly lower mean number of immature dendritic cells with respect to that found in controls. The mean number of mature dendritic cells was also lower in patients than in controls, without, however, significant differences. Finally, surgery induced a statistically significant decline in the mean number of both immature and mature dendritic cells, and the decrease was particularly pronounced for immature dendritic cells. CONCLUSIONS: In addition to the well-demonstrated surgery-induced lymphocytopenia, this preliminary study shows that the surgical treatment may determine a significant decrease in circulating immature and mature dendritic cells. Because of the fundamental role of dendritic cells in regulating the immune responses, surgery-induced decline in circulating dendritic cells number could play a role in determining the immunosuppressive status, which characterizes the postoperative period.
Adult↗
A phase II study of subcutaneous low-dose interleukin-2 plus erythropoietin in metastatic renal cell carcinoma progressing on interleukin-2 alone.
OBJECTIVE: The activation of angiogenesis has been proven to suppress the anti-cancer immunity. The evidence of abnormally high pretreatment blood levels of vascular endothelial growth factor (VEGF), which is the main angiogenic factor, has appeared to predict resistance to IL-2 immunotherapy of metastatic renal cell carcinoma (RCC). Therefore, the control of VEGF secretion could influence the efficacy of IL-2. Recent data suggest that erythropoietin (EPO) may modulate VEGF secretion and IL-2 biological activity. On this basis, a study was planned with subcutaneous (s.c.) low-dose IL-2 plus EPO in metastatic RCC, which had progressed on IL-2 alone (6 million IU/day for 6 days/week for 4 weeks). METHODS: Patients received IL-2 at the same dose as the previous cycle, plus EPO (10,000 3 times/week until the end of IL-2 therapy. Serum levels of VEGF were measured by enzyme immunoassay on venous blood samples collected at weekly intervals. The study included 12 evaluable metastatic RCC patients. RESULTS: The treatment was well-tolerated and most patients referred a relief of IL-2-induced asthenia. A partial response (PR) and 4 stable diseases (SD) were achieved on IL-2 plus EPO, whereas the other 7 patients had a progressive disease (PD). Hemoglobin mean levels were significantly higher on IL-2 plus EPO than during the previous therapy with IL-2 alone in the same patients. In the same way, mean lymphocyte increase was higher on IL-2 plus EPO than on IL-2 alone, even though this difference was not significant. Finally, VEGF increase was significantly lower on IL-2 plus EPO than during IL-2 alone. CONCLUSION: This preliminary study shows that the concomitant administration of EPO may allow a control of the neoplastic growth in advanced cancer patients progressing on IL-2 alone, reduce the subjective toxicity, prevent hemoglobin decrease and counteract IL-2-related VEGF increase.
Aged↗
Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1.
Elevated VEGF blood concentrations have been proven to be associated with poor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its angiogenic activity, may also play an immunosuppressant role by inhibiting dendritic cell (DC) maturation. The present study was performed to analyze blood levels of VEGF in cancer patients in relation to those of another potentially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absolute number of circulating immature and mature DC, and serum levels of the best known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric cancer: 17; cancer of pancreas: 4; lung cancer: 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ metastases. In each patient, we have evaluated serum concentrations of VEGF-165, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123+) and mature (CD11c+) DC. Mean serum levels of VEGF-165 were significantly higher in metastatic patients than in controls or in non-metastatic patients, whereas the total amounts of VEGF were not significantly higher. Moreover, it has been observed that patients with abnormally elevated blood concentrations of VEGF-165 showed significantly lower mean values of immature DC, mature DC and IL-12 and significantly higher mean levels of ET-1 than those with normal concentrations. This study, by confirming that advanced neoplastic disease may be associated with increased endogenous secretion of VEGF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulation of the neovascularization, but also on VEGF-related immunosuppression.
Adult↗
Abrogation of surgery-induced IL-6 hypersecretion by presurgical immunotherapy with IL-2 and its importance in the prevention of postoperative complications.
Because of its immunosuppressive effect, surgery-induced immunosuppression may depend at least in part on the postoperative hypersecretion of IL-6, which is also responsible for surgical complications. Most of the immunosuppressive events induced by surgery, including lymphocytopenia, NK and T lymphocyte decline, and dendritic cell deficiency have been proven to be abrogated by a preoperative injection of IL-2 for few days. However, the cytokine mechanisms responsible for IL-2-induced abrogation of surgery-related immunosuppression need to be better investigated and understood. This study was performed to analyze the influence of IL-2 presurgical immunotherapy on IL-6 secretion in the postoperative period. The study was performed in 12 operable colorectal cancer patients, who were preoperatively pretreated with IL-2 (12 million lU/day subcutaneously for 3 consecutive days before surgery). The control group consisted of 21 age-and disease-matched colorectal cancer patients who underwent surgery without a preoperative immunotherapy with IL-2. Serum levels of IL-6 were measured by an enzyme immunoassay before surgery, and at days 3 and 7 of the postoperative period. A significant increase in mean serum levels of IL-6 occurred in the postoperative period only in the control patients, whereas in the IL-2 pretreated group no significant difference was seen between presurgical and postoperative IL-6 mean concentrations. The difference between controls and IL-2 group was particularly evident for patients with abnormally elevated presurgical values of IL-6. This study, by showing that a presurgical injection of IL-2 may prevent surgery-induced IL-6 enhanced secretion, would suggest that the previously described neutralization of surgery-induced immunosuppression by IL-2 preoperative immunotherapy may depend at least in part on the inhibition of postoperative production of IL-6, whose immunosuppressive effects have been well demonstrated at least on anticancer immunity.
Aged↗
A phase II study of chemoneuroimmunotherapy with platinum, subcutaneous low-dose interleukin-2 and the pineal neurohormone melatonin (P.I.M.) as a second-line therapy in metastatic melanoma patients progressing on dacarbazine plus interferon-alpha.
Immunochemotherapeutic combinations containing IL-2 theoretically represent the most effective therapies for metastatic melanoma, particularly in association with cisplatin (CDDP); however, both IL-2 and CDDP have been generally utilized at high doses, with the consequence of considerable toxicity. According to psychoneuroimmunological knowledge, the antitumor activity of IL-2 has been proven to be enhanced by the immunomodulating pineal neurohormone melatonin (MLT), which has also been shown to increase the cytotoxicity of cancer chemotherapy and reduce its toxicity. On this basis, a study was planned with low-dose IL-2 and CDDP in association with MLT as a second-line therapy for metastatic melanoma patients progressing on dacarbazine plus interferon-alpha. The study included 13 evaluable patients. CDDP was injected i.v. at 30 mg/m2/day for 3 days every 21 days. IL-2 was administered s.c. at 3 million IU/day from days 4 to 9 and from days 11 to 16 of the cycle. Finally, MLT was given orally at 20 mg/day in the evening, every day without interruption. One patient obtained a complete response (CR), while partial response (PR) was achieved in 3 other patients. Therefore, the objective tumor response-rate (CR + PR) was 4 out of 13 (31%). A stable disease occurred in 5 patients, whereas the remaining 4 patients had a progressive disease. The treatment was extremely well-tolerated in all patients and, in particular, no CDDP-related neurotoxicity was observed. The results of this preliminary study would suggest that low-dose CDDP and IL-2 in association with the pineal hormone MLT (P.I.M. schedule), given as a second line therapy, is an effective and well-tolerated treatment for metastatic melanoma, with a clinical efficacy at least comparable to that obtained with a first-line therapy of dacarbazine plus interferon-alpha.
Aged↗
Ten-year survival results in metastatic renal cell cancer patients treated with monoimmunotherapy with subcutaneous low-dose interleukin-2.
After more than ten years of clinical investigations, IL-2 immunotherapy appears to constitute the most effective treatment metastatic renal cell carcinoma (RCC),at least in terms of survival time. Moreover, it has been shown that comparable results may be achieved with different schedules of treatment, including intravenous high-dose or subcutaneous (SC) low-dose IL-2. Finally, it has been demonstrated that the association with interferon-alpha does not increase the efficacy of IL-2. Therefore, SC low-dose IL-2 alone may be considered as an adequate therapy for metastatic RCC. In fact, our previous studies with SC low-dose IL-2 alone have shown a 5-year survival time similar to that described with higher and more toxic doses of IL-2. This study was performed to analyze the 10-year survival results with SC low-dose IL-2 in metastatic RCC The study included 44 consecutive metastatic RCC patients, with a minimum follow-up of 120 months. One comlete immunotherapeutic cycle consisted of IL-2 at 3 million IU twice/day SC, 5 days/week for 6 consecutive weeks. In non-progressing patients, a second cycle was planned after a 21-day rest period. Complete response (CR) was achieved in only 2 out of 44 (4%) patients, while partial response (PR) was obtained in 8 out of /44 (18%) patients. Therefore, the response rate (CR + PR) was 10 out of 44 (22%), with a median response duration of 12 months. Stable disease (SD) occurred in 21 out of 44 (48%) patients,whereas the remaining 13 out of 44 (30%) patients had a progressive disease (PD). A 10-year survival was achieved in 2 out of 44 (5%) and the percent of survival at 10 years was significantly higher in patients with response or SD than in those with PD. This study confirms at 10 years the results previously referred to by other authors and by ourselves, in showing that the efficacy of IL-2 immunotherapy in terms of control of cancer growth is associated with a clear prolongation of the overall survival time in metastatic RCC.
Adult↗
Clinical and biological effects of interleukin-2 with or without a concomitant administration of granulocyte-macrophage colony-stimulating factor in metastatic cancer patients.
GM-CSF has been shown to modulate the anticancer activity of IL-2 with, however, controversial results depending on the great variety of biological effects induced by GM-CSF itself. The activation of dendritic cells and the generation of suppressive cells would constitute the main favourable and unfavourable biological effects of GM-CSF, respectively. The present study was performed in an attempt to evaluate the clinical and biological effects of a concomitant GM-CSF administration of the immunotherapy of metastatic renal cell carcinoma with IL-2. The study included 25 patients, who were randomized to be treated with IL-2 alone or IL-2 plus GM-CSF. IL-2 was injected subcutaneously at 6 MIU/day for 6 days/week for 4 consecutive weeks, coressponding to one complete cycle. GM-CSF was injected subcutaneously at 0.3 micrograms/kg b.w. for 3 consecutive days for the first 3 days of each week of IL-2 administration. Two immunotherapeutic cycles at 21-day intervals were planned. No significant difference was observed in the percent of non-progressive disease between the two groups of patients. The increase in leukocyte mean number was significantly higher in patients concomitantly treated with GM-CSF, whereas no difference was observed in that of lymphocytes. This preliminary study suggests that the concomitant administration of GM-CSF does not enhance the therapeutic efficacy of IL-2 immunotherapy of metastatic renal cell cancer.
Aged↗
Enhancement of the efficacy of chemotherapy with oxaliplatin plus 5-fluorouracil by pretreatment with IL-2 subcutaneous immunotherapy in metastatic colorectal cancer patients with lymphocytopenia prior to therapy.
The present study was carried out to evaluate the influence of a short-period IL-2 administration on the efficacy of chemotherapy in metastatic colorectal cancer patients with pretreatment lymphocytopenia, which was defined as a lymphocyte count of less than 1500/mm3. The study included 144 consecutive metastatic colorectal cancer patients, who underwent chemotherapy with oxaliplatin plus 5-fluorouracil. Lymphocytopenia was seen in 41/144 (28%) patients, who were randomized to receive chemotherapy alone or chemotherapy after a prechemoimmunotherapy with IL-2 (3 MIU twice/day for 3 consecutive days), whereas patients with a normal pretreatment lymphocyte count received only chemotherapy. A normalization of the lymphocyte number was achieved in 12/19 lymphocytopenic patients pretreated with IL-2. The objective tumor regression rate achieved in patients with a normal lymphocyte count prior to chemotherapy was significantly higher compared to that obtained in lmphocytopenic patients treated with chemotherapy alone (54/103 vs. 3/22, p < 0.01), whereas no significant difference occurred between patients with normal lymphocyte count and lymphocytopenic patients pretreated with IL-2 (54/103 vs. 8/19). This study confirms that pretreatment lymphocytopenia is associated with reduced efficacy of chemotherapy in metastatic colorectal cancer patients. Moreover, it suggests that pretreatment with IL-2 before the onset of chemotherapy may enhance the efficacy of chemotherapy in lymphocytopenic patients. Therefore, the administration of IL-2 before the onset of chemotherapy to improve the immune status of cancer patients may be considered as a new chemoimmunotherapeutic combination, which may be recommended in the treatment of advanced cancer patients, particularly in those with cancer-related immune alterations.
Adult↗
[The ultrastructure of the steroidogenic cells of the mammalian ovary. Certain conditions of the interstitial cell of the mouse ovary].
Explore the source record for details and available documents.
Animals↗
A study of interactions among markers of macrophage functions in metastatic solid tumors: neopterin levels in relation to those of tumor necrosis factor-alpha and of soluble interleukin-2 receptors.
High levels of the macrophage activation marker neopterin have been described in metastatic cancer patients. Since macrophages may either counteract or stimulate tumor development, it is important to establish which macrophage activity is mainly related to neopterin release. The present study was carried out to evaluate neopterin levels in metastatic solid tumor patients in respect with the antitumor macrophage cytokine TNF and with soluble IL-2 receptor (SIL-2R), whose secretion is stimulated by macrophages and it is associated with the immunosuppressive status of cancer patients. The study included 35 patients with metastatic solid neoplasms. Serum levels of neopterin, TNF and SIL-2R were measured in blood samples collected during the morning. Abnormally high concentrations of neopterin were seen in 18/35 (51%) patients. Patients with high levels of neopterin showed significantly higher concentrations of SIL-2R than those with normal neopterin values, whereas no difference was found in TNF levels. This study would suggest that the increased secretion of neopterin may reflect macrophage-mediated immunosuppression in metastatic solid neoplasms, rather than to be associated with the antitumor activity of macrophages.
Adult↗
Immune effects of preoperative immunotherapy with high-dose subcutaneous interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the neurohormone melatonin in gastrointestinal tract tumor patients.
Surgery-induced immunosuppression could influence tumor/host interactions in surgically treated cancer patients. Previous studies have shown that high-dose IL-2 preoperative therapy may neutralize surgery-induced lymphocytopenia. Moreover, experimental studies have demonstrated that the immunomodulating neurohormone melatonin (MLT) may amplify IL-2 activity and reduce its dose required to activate the immune system. On this basis, we have compared the immune effects of presurgical therapy with high-dose IL-2 with respect to those obtained with preoperative neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study included 30 patients with gastrointestinal tract tumors, who were randomized to undergo surgery alone, or surgery plus a preoperative biotherapy with high-dose IL-2 (18 million IU/day subcutaneously for 3 days) or low-dose IL-2 (6 million IU/day subcutaneously for 5 days) plus MLT (40 mg/day orally). Patients underwent surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to prevent surgery-induced lymphocytopenia. However, mean number of lymphocytes, T lymphocytes and T helper lymphocytes observed on day 1 of postoperative period was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. Moreover, toxicity was less in patients treated with IL-2 and MLT. This biological study shows that both immunotherapy with high-dose IL-2 or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively are tolerated biotherapies, capable of neutralizing surgery-induced lymphocytopenia in cancer patients. Moreover, the study would suggest that the neuroimmunotherapy may induce a more rapid effect on postoperative immune changes with respect to IL-2 alone.
Adult↗
Treatment of cancer-related thrombocytopenia by low-dose subcutaneous interleukin-2 plus the pineal hormone melatonin: a biological phase II study.
Despite the platelet production in response to IL-2, cancer immunotherapy with IL-2 tends to induce thrombocytopenia, which probably depends on an enhanced peripheral destruction. On the basis of our previous studies, this effect may be neutralized by a concomitant administration of the pineal hormone melatonin (MLT). This study was performed to investigate the influence of an immunotherapeutic combination with low-dose IL-2 and MLT on platelet number in advanced cancer patients showing persistent thrombocytopenia. The study included 14 advanced solid tumor patients, affected by thrombocytopenia due to different causes (portal hypertension: 9; previous chemotherapies: 3; DIC: 2). IL-2 was injected at 3 million IU/day subcutaneously for 6 days/week for 4 weeks, in association with MLT (40 mg/day orally). A normalization of platelet number occurred in 10/14 (71%) patients, and platelet mean number significantly increased on treatment. No important therapy-related toxicity was observed. This preliminary study would suggest that the concomitant administration of MLT is able not only to neutralize IL-2-induced thrombocytopenia, but also to increase platelet number in thrombocytopenic cancer patients.
Adult↗