Biomedical subjects

S Barni

Publications and source records attributed to S Barni.

At least 109 records · Page 6Linked to original sources

PubMed1994

A randomized study of immunotherapy with low-dose subcutaneous interleukin-2 plus melatonin vs chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small cell lung cancer.

AIMS AND BACKGROUND: The therapeutic role of chemotherapy in advanced non-small cell lung cancer (NSCLC) is controversial because of its potentially detrimental action on host anticancer defenses. On the contrary, IL-2 would seem to prolong survival time by improving the immune status, even though it is generally less effective in determining tumor regression in NSCLC. Our previous studies have suggested the possibility of increasing tumor sensitivity to IL-2 by concomitant administration of immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On this basis, a study was carried out to evaluate the efficacy of immunotherapy with low-dose IL-2 plus MLT versus chemotherapy in advanced NSCLC. METHODS: The study included 60 patients with locally advanced or metastatic NSCLC, who were randomized to receive immunotherapy or chemotherapy. The immunotherapy consisted of IL-2 (3 million IU/day subcutaneously for 6 days/week for 4 weeks) and MLT (40 mg/day orally every day, starting 7 days before IL-2); in nonprogressing patients, a second cycle was repeated after a 21-day rest period, then they underwent a maintenance period consisting of one week of therapy every month until progression. Chemotherapy consisted of cisplatin (20 mg/m2) and etoposide (100 mg/m2)/day intravenously for 3 days; cycles of chemotherapy were repeated every 21 days until progression. RESULTS: No complete response was obtained. A partial response was achieved in 7/29 patients treated with chemotherapy and in 6/31 patients receiving chemotherapy. The difference was not significant. In contrast, the mean progression-free period and the percentage survival at 1 year was significantly higher in patients treated with immunotherapy than in those treated with chemotherapy. Toxicity was substantially lower in patients receiving immunotherapy than in those given chemotherapy. CONCLUSIONS: This randomized study showed that immunotherapy with low-dose IL-2 plus MLT is a better tolerated and more effective therapy in terms of survival time than chemotherapy containing cisplatin in patients affected by advanced NSCLC.

Adult↗

PubMed1994

Pineal-opioid system interactions in the control of immunoinflammatory responses.

Several studies have demonstrated involvement of the pineal gland in the regulation of neuropeptide secretion and activity. In particular, the existence of links between the pineal gland and the brain opioid system has been documented. Both opioid peptides and melatonin (MLT), the most investigated pineal hormone, play an important role in neuromodulation of the immunity. Moreover, the immune effects of MLT are mediated by endogenous opioid peptides, which may be produced by both the endocrine system and the immune cells. In addition, the immune dysfunctions that characterize some human diseases, such as cancer, depend not only on the immune system per se, but also at least in part, on altered secretion of immunomodulating neurohormones, including MLT and opioid peptides. Therefore, the exogenous administration of neurohormones could potentially improve the immune status in humans. The present study evaluates the effects of MLT on changes in the number of T lymphocytes, natural killer cells, and eosinophils induced by exogenous administration of interleukin-2 (IL-2). Macrophage activity was also evaluated by determining serum levels of its specific marker, neopterin. The study was performed in 90 patients with advanced solid neoplasms, who received IL-2 at a dose of 3 million IU/day subcutaneously for 6 days a week for 4 weeks plus MLT at a daily dose of 40 mg. Both drugs were given in the evening. The results were compared to those in 40 cancer patients treated with IL-2 alone. The mean increase in T lymphocytes, natural killer cells, and eosinophils was significantly higher in patients treated with IL-2 plus MLT than in those who received IL-2 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Vinorelbine as single agent in pretreated patients with advanced breast cancer.

Vinorelbine is a new semisynthetic vinca alkaloid with high activity against breast cancer. In this multicenter clinical study we evaluated the activity and toxicity of vinorelbine as a single agent in 30 advanced breast cancer patients pretreated with anthracycline and/or mitoxantrone (24 with recurrent tumor, 6 with non operable cancers). Vinorelbine was given at a weekly dose of 20 mg/m2 for a minimum of 3 weeks. Treatment was continued until there was disease progression or evidence of serious toxicity. Predominant sites of metastasis were viscera (14 cases), soft tissue (11 cases) and bone (5 cases). A median number of 12 doses of vinorelbine (range 3-34) were administered to each patient. Objective responses were recorded in 11 of them and 15 had minimal responses or stable disease. Four patients showed progression of disease during vinorelbine chemotherapy. The median duration of response was 5 months (2-14). The median survival time was 7 months (2-20+): 9 months for responders and 5 months for those with stable or progressive disease. The most important and dose-limiting toxicity was represented by leukopenia. The compliance of patients was very good and the treatment was well accepted by them all including those with low performance status. In conclusion, this study provides further evidence that a weekly schedule with vinorelbine as a single agent is effective and well-tolerated also in pretreated advanced breast cancer patients.

Adult↗

PubMed1994

Lymphocytosis decline is not responsible for tumor progression in cancer patients chronically treated with interleukin-2.

AIMS AND BACKGROUND: The antitumor activity of IL-2 is mediated by an increase in lymphocyte number. Moreover, our previous studies have shown that therapy for 1 week/month with low-dose subcutaneous IL-2 is sufficient to maintain high levels of lymphocytes in cancer patient who have had tumor regression or stable disease (SD) in response to IL-2 immunotherapeutic cycles. This study was performed to establish whether tumor progression in cancer patients chronically treated with IL-2 may be associated with lymphocyte number decline. METHODS: The study included 53 metastatic renal cell cancer patients, who were treated with 2 induction cycles of IL-2 subcutaneous immunotherapy (6 million IU/day for 5 days/week for 6 weeks, corresponding to one cycle). Tumor regression occurred in 15/53 patients, 20 patients had a SD, and the remaining 18 cases progressed. Non progressed patients (n = 35) underwent a maintenance therapy consisting of one week of therapy every month. After a median follow-up of 18 months, 26/35 patients with response or SD had progressed. The immune investigation consisted of lymphocyte, T lymphocyte, NK cell number determination and sCD25 level detection. RESULTS: The mean number of lymphocytes, T lymphocytes and NK cells observed on IL-2 maintenance therapy was significantly higher than that seen before beginning the immunotherapy. Moreover, mean number of lymphocytes and mean levels of sCD25 observed at the time of tumor progression were respectively lower and higher than those seen on maintenance therapy in the same patients, without, however, significant differences. CONCLUSION: Despite the importance of lymphocytes in mediating the antitumor activity of IL-2, this study shows that tumor progression in cancer patients chronically treated with low-dose IL-2 after response or SD during IL-2 induction cycles is not associated with a significant decline in lymphocyte, T lymphocyte or NK cell numbers. Further studies, carried out to analyze the functional status of immune cells at the time of tumor progression, will be necessary to define the role of immunity in cancer patients progressing under IL-2 chronic therapy.

Carcinoma, Renal Cell↗

PubMed1994

Ondansetron does not stimulate prolactin release in breast cancer patients.

AIMS AND BACKGROUND: Prolactin (PRL) may be a tumor growth factor, mainly for breast cancer. The antidopaminergic drugs commonly used in the treatment of chemotherapy-induced vomiting stimulate PRL release, and this finding could represent a potentially negative biologic event for cancer patients. This study was performed to analyze PRL response to the serotonin-type 3 receptor antagonist ondansetron, a new active drug in the treatment of vomiting due to chemotherapy, in cancer patients. METHODS: The study included 8 premenopausal breast cancer patients undergoing adjuvant chemotherapy. Ondansetron was given intravenously at a dose of 8 mg, and venous blood samples were drawn at 0, 20, 60 and 120 min. The result were compared to those seen in 10 breast cancer patients treated with metoclopramide (10 mg. i.v.). RESULTS: PRL mean levels significantly increased in response to metoclopramide. In contrast, no significant changes in PRL mean values occurred after ondansetron injection. CONCLUSIONS: The study showed that ondansetron, whose efficacy in the treatment of chemotherapy-induced vomiting is well known, does not stimulate the tumor growth factor PRL in cancer patients, in contrast the the action of the most commonly used antidopaminergic drugs.

Adult↗

PubMed1994

Serum levels of insulin-like growth factor-I in operable breast cancer in relation to the main prognostic variables and their perioperative changes in relation to those of prolactin.

AIMS AND BACKGROUND: In addition to estrogens, prolactin (PRL) and IGF-I have also appeared to stimulate breast cancer growth. The present study was performed to evaluate IGF-I blood levels in operable breast cancer in relation to PRL values and the main prognostic variables. METHODS: The study included 40 patients, clinical stage T1-3NO-2MO. Venous blood samples were collected before and 7 days after surgery. PRL and IGF-I were measured by radioimmunoassay. The control group consisted of 50 healthy women. RESULTS: Mean serum levels of IGF-I were significantly higher in patients than in controls, without any apparent relation to the main prognostic variables, including estrogen receptor and node status. Surgery-induced hyperprolactinemia occurred in 22/40 patients. IGF-I mean concentrations observed in the postoperative period in patients with surgery-induced hyperprolactinemia were significantly lower than those seen in patients showing no postoperative PRL rise. CONCLUSIONS: The study showed that operable breast cancer may be associated with abnormally high levels of tumor growth factor IGF-I, and that surgery was followed by an IGF-I decline only in patients who showed surgery-induced hyperprolactinemia. Our previous studies have shown that postoperative hyperprolactinemia is a favorable prognostic factors for operable breast cancer. The present study, by showing that a postoperative PRL rise is associated with a fall in IGF-I, would suggest that surgery-induced hyperprolactinemia may determine a lower tumor relapse rate by determining a diminished secretion of breast tumor growth factor IGF-I.

Adult↗

PubMed1994

A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms.

BACKGROUND: Unresectable brain metastases remain an untreatable disease. Because of its antitumor cytostatic action and its anticonvulsant effect, the pineal hormone melatonin could constitute a new effective agent in the treatment of brain metastases. The current study was performed to evaluate the effect of melatonin on the survival time in patients with brain metastases due to solid neoplasms. METHODS: The study included 50 patients, who were randomized to be treated with supportive care alone (steroids plus anticonvulsant agents) or with supportive care plus melatonin (20 mg/day at 8:00 p.m. orally). RESULTS: The survival at 1 year, free-from-brain-progression period, and mean survival time were significantly higher in patients treated with melatonin than in those who received the supportive care alone. Conversely, steroid-induced metabolic and infective complications were significantly more frequent in patients treated with supportive care alone than in those concomitantly treated with melatonin. CONCLUSIONS: The pineal hormone melatonin may be able to improve the survival time and the quality of life in patients with brain metastases due to solid tumors.

Adult↗

PubMed1994

Double modulation of 5-fluorouracil in advanced colorectal cancer with low-dose interferon-alpha 2b and folinic acid. The "GISCAD" experience. Italian Group for the Study of Digestive Tract Cancer.

In advanced colorectal cancer the addition of folinic acid (FA) has been shown to lead to increased activity, at least in terms of response rate, in comparison with 5-fluorouracil (5FU) alone. Similarly, interferon-alpha (IFN) is able to potentiate 5FU, although high doses cause heavy toxicity. Given the different mechanisms of action of the two agents, the double modulation of 5FU deserves clinical evaluation. In a multicenter study (involving both primary care and referral institutions) 63 patients with advanced colorectal cancer, previously untreated with chemotherapy, received, in an outpatient setting, FA (200 mg/m2 i.v. bolus) + 5FU (400 mg/m2 i.v. in 15 min) for 5 consecutive days every 4 weeks + IFN 3 x 10(6) U on alternate days, starting 1 week before chemotherapy. During the 5 days of 5FU + FA, IFN was administered daily. The antitumour activity, the impact on response duration and survival and toxicity of the combination were evaluated according to WHO criteria. Of the 63 enrolled patients, 56 were evaluable: there were 2 complete responses (3%) and 13 partial responses (21%), giving an objective response rate of 24% (95% confidence interval 13-35%); no change was observed in 17 cases and progressive disease in 24. Median duration of response was 9 months and median survival (all patients) 13 months. Toxicity was acceptable, even though 4 patients presented reversible grade 4 side-effects (2 mucositis and 2 diarrhoea). With this schedule and these doses, addition of IFN did not lead to any increase in the activity of 5FU + FA. In colorectal cancer, further clinical studies with these drugs should be based on a deeper experimental knowledge of their mechanisms of interaction.

Adult↗

PubMed1994

Low-dose interleukin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma.

Experimental studies have showed that hepatocellular carcinoma (HCC) cells are susceptible to cytolysis of interleukin (IL)-2-activated lymphocytes. Moreover, our previous studies demonstrated that the pineal neurohormone melatonin (MLT) may enhance IL-2 efficacy. On this basis, a study was started with low-dose IL-2 (3 million U/day subcutaneously for 6 days/week for 4 weeks) plus MLT (50 mg/day orally every day given in the evening) as a first-line therapy of unresectable HCC. The study included 14 patients. Objective tumour regressions were obtained in 5/14 (36%) patients (one complete response, four partial responses), with a median duration of 7+ months. 6 patients had stable disease, while the other 3 progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapy with low-dose IL-2 plus MLT is a new well-tolerated and effective therapy of advanced HCC.

Adult↗

PubMed1994

A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma.

Our previous experimental studies have shown that the best approach to increase the biological anti-tumour activity of interleukin 2 (IL-2) is not co-administration of another cytokine, but the association with immunomodulating neurohormones, in an attempt to reproduce the physiological links between psychoendocrine and immune systems, which play a fundamental role in the regulation of the immune responses. In particular, the association with the pineal neurohormone melatonin (MLT) has been shown to cause tumour regressions in neoplasms that are generally non-responsive to IL-2 alone. To confirm these preliminary results, a clinical trial was performed in locally advanced or metastatic patients with solid tumours other than renal cell cancer and melanoma. The study included 80 consecutive patients, who were randomised to be treated with IL-2 alone subcutaneously (3 million IU day-1 at 8.00 p.m. 6 days a week for 4 weeks) or IL-2 plus MLT (40 mg day-1 orally at 8.00 p.m. every day starting 7 days before IL-2). A complete response was obtained in 3/41 patients treated with IL-2 plus MLT and in none of the patients receiving IL-2 alone. A partial response was achieved in 8/41 patients treated with IL-2 plus MLT and in only 1/39 patients treated with IL-2 alone. Tumour objective regression rate was significantly higher in patients treated with IL-2 and MLT than in those receiving IL-2 alone (11/41 vs 1/39, P < 0.001). The survival at 1 year was significantly higher in patients treated with IL-2 and MLT than in the IL-2 group (19/41 vs 6/39, P < 0.05). Finally, the mean increase in lymphocyte and eosinophil number was significantly higher in the IL-2 plus MLT group than in patients treated with IL-2 alone; on the contrary, the mean increase in the specific marker of macrophage activation neopterin was significantly higher in patients treated with IL-2 alone. The treatment was well tolerated in both groups of patients. This study shows that the concomitant administration of the pineal hormone MLT may increase the efficacy of low-dose IL-2 subcutaneous therapy.

Adult↗

PubMed1994

Vinorelbine is an active antiproliferative agent in pretreated advanced breast cancer patients: a phase II study.

PURPOSE: To evaluate the efficacy and toxicity of single-agent vinorelbine (VNB), a semisynthetic vinca alkaloid, in patients with breast cancer previously treated with other chemotherapeutic regimens for metastatic disease. PATIENTS AND METHODS: Sixty-seven of 70 patients with assessable disease entered onto the study were assessable. The main characteristics were as follows: median age, 60 years (range, 41 to 77); median performance status (PS; Karnofsky score), 90 (range, 60 to 100); and number of previous chemotherapeutic regimens given--one in 17, two in 27, three in eight, four in two, and five in one patient. The dominant sites of metastasis were viscera in 40, bone in 16, and soft tissues in 11 patients. VNB was administered beginning with the dose of 20 mg/m2 by 60-minute intravenous (iv) infusion weekly, with a dose escalation up to 25 mg/m2 if the first four courses were well tolerated. The treatment was continued until disease progression. RESULTS: Overall, 845 courses of VNB were given (median, 10; range, eight to 33). Objective responses were as follows: complete response (CR) in three (4.5%), partial response (PR) in 21 (31.2%), stable disease (SD) in 20 (30%), and progressive disease (PD) in 23 patients (34.3%). Twenty-four of 67 assessable patients obtained a major objective response (CR or PR, 36%; 95% confidence interval [Cl], 24% to 47%). Thirty-three percent of patients had a > or = 33% reduction of dose-intensity (DI). The median time to progression was 18 weeks. The drug was active in patients pretreated with either cyclophosphamide, methotrexate, and fluorouracil (CMF) or anthracyclines. The most relevant toxicity observed was myelosuppression: 17 (25%) and 19 patients (28%) had World Health Organization grade III, and six (9%) and six patients (9%) had grade IV leukopenia and granulocytopenia, respectively; two (3%) and two patients (3%) had grade III and IV anemia, respectively. Nonhematologic toxicities were phlebitis (grade II or III in 15 patients), alopecia (grade I or II in 16), nausea and vomiting (grade II or III in 15), diarrhea (grade II in two), constipation (grade II or III in 16), stomatitis (grade II or III in 13), peripheral neuropathy (grade II in seven), and asthenia (grade II in five). CONCLUSION: This study shows that VNB is an effective and well-tolerated agent in pretreated patients with advanced breast cancer. This drug does not seem to present cross-resistance with previous CMF or anthracycline regimens. Future clinical trials should be designed to prove whether the inclusion of VNB in combination chemotherapy regimens, or whether an enhancement of its dose-intensity using bone marrow growth factors, is able to improve further the efficacy of this drug in breast carcinoma.

Adult↗

PubMed1994

Correlation between ultrastructural and histochemical parameters in lymphokine-activated killer (LAK) cells reacting with target cells in vitro.

Ultrastructural and fluorescence data allowed us to study the most important moments of the interaction between lymphokine-activated killer (LAK) cells against target cells (Chang) in vitro. The LAK cells, maintained at low doses of recombinant interleukin-2, were able to recognize, bind and destroy the tumoral cells. Before the attack, the LAK cells were characterized by a cytoplasm with a high ribosomes content; after the identification and the interaction cell-cell, a degeneration of the tumoral cell was observed. These observations allowed us to suppose that the interaction between the two types of cells may be mediated by a receptoral membrane system without the action of lytic enzymes.

Autolysis↗

PubMed1993

A randomized study of low-dose interleukin-2 subcutaneous immunotherapy versus interleukin-2 plus interferon-alpha as first line therapy for metastatic renal cell carcinoma.

AIMS AND BACKGROUND: IL-2 given subcutaneously in combination with interferon-alpha 2b (IFN) appears to induce a response rate comparable to that obtained with IL-2 intravenous injection in patients with metastatic renal cell carcinoma (RCC) but with lower toxicity. The role of IFN when combined with IL-2 has however still to be defined. The present study was performed to draw some preliminary conclusions about the effect of IFN in combination with IL-2 in metastatic RCC. METHODS: The study included 30 consecutive patients with metastatic RCC who were randomized to treatment with IL-2 subcutaneous therapy (3 million IU twice/daily for 5 days/week for 6 weeks) or with IL-2 plus IFN (5 million U/m2 subcutaneously thrice weekly). In patients without progressive disease, a second cycle was repeated after a 28-day rest period. RESULTS: No significant difference in partial response rate was found between patients treated with IL-2 alone and those given IL-2 plus IFN (5/15 vs 4/15). Similarly, no difference was seen in the percentage of stable disease (7/15 vs 7/15). Toxicity was higher in patients who received IL-2 plus IFN. Lymphocyte and eosinophil mean increase was higher in patients treated with IL-2 alone than in those treated with IL-2 plus IFN, without however any significant difference. CONCLUSIONS: The present results, which require confirmation in a larger series, indicate that combination with IFN does not increase the efficacy of IL-2 subcutaneous immunotherapy in metastatic RCC but only the toxicity of treatment.

Adjuvants, Immunologic↗

PubMed1993

Subcutaneous therapy with low-dose interleukin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status.

AIMS AND BACKGROUND: Patients with disseminated gastric cancer are generally in very bad clinical conditions, which make them not eligible for potentially active polychemotherapies. This justifies the development of less toxic therapies such as the use of biological response modifiers. Unfortunately, IL-2, one of the most promising cytokines, does not seem to be effective in gastric cancer. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify IL-2 activity, which becomes biologically effective also at very low doses. Based on these considerations, a pilot study was performed with low-dose subcutaneous IL-2 in combination with MLT in metastatic gastric cancer patients with low performance status. METHODS: The study included 14 patients with metastatic gastric cancer who received IL-2 at a dose of 3 million IU/day at 8.00 p.m. subcutaneously for 6 days/week for 4 weeks. MLT was given orally at a dose of 50 mg/day at 8.00 p.m. every day starting 7 days before IL-2. In patients in whom the disease did not progress, a second cycle was given after a rest period of 21 days. RESULTS: A tumor regression was obtained in 3/14 (21%) patients, complete response in 1 and partial in 2, with a median duration of 13 + months. The disease stabilized in 6/14 (43%) patients and progressed in the remaining 5 (36%). Survival was significantly longer in patients with response or stable disease than in those with progression. Toxicity was low in all cases. CONCLUSIONS: These preliminary results show that the combination on of low-dose subcutaneous IL-2 and the pineal hormone MLT may represent a new well tolerated biotherapy, capable of inducing objective tumor regression also in patients with metastatic gastric cancer and low performance status.

Aged↗

PubMed1993

Immunotherapy with low-dose subcutaneous interleukin-2 plus beta-interferon as a second-line therapy for metastatic colorectal carcinoma.

AIMS AND BACKGROUND: Beta-interferon (beta-IFN) has been proven to influence some IL-2-induced immune effects. On the basis of these experimental data, we evaluated the immunobiologic effects of an association between very low-dose IL-2 and beta-IFN in advanced cancer patients. METHODS: The study was performed in 15 metastatic colon cancer patients, who progressed in response to a first-line chemotherapy with 5-FU plus folates. IL-2 was given subcutaneously at a daily dose of 3 million IU in the evening for 6 days/week for 4 weeks. beta-IFN was injected subcutaneously at a dose of 3 million U/day for 7 days before the first IL-2 injection, then thrice/week until the end of IL-2 administration. In nonprogressed patients, a second cycle was given after a 14-day rest period. RESULTS: No objective tumor regression was seen. Stable disease was obtained only in 2/15 patients; the other 13 progressed. Toxicity was low in all cases. Natural killer cell and T-activated lymphocyte mean number significantly increased during the immunotherapy. Lymphocyte and eosinophil mean number also increased, without, however, significant differences. IL-2-induced suppressive events, consisting of an increase in T-suppressor cell number, and soluble IL-2 receptor levels were not blocked by beta-IFN. CONCLUSIONS: The study showed that the concomitant administration of beta-IFN may determine an improvement in the immune performance in metastatic cancer patients treated with very low-dose IL-2, even though this biologic improvement does not seem to be associated to a control of tumor development. Further studies in patients with less advanced disease are needed to better define the impact of the immune improvement induced by low-dose IL-2 plus beta-IFN on the clinical course of the neoplastic disease.

Adult↗

PubMed1993

Immunoendocrine therapy with interleukin-2 (IL-2) and medroxyprogesterone acetate (MPA): a randomized study with or without MPA in metastatic renal cancer patients during IL-2 maintenance treatment after response or stable disease to IL-2 subcutaneous therapy.

AIMS AND BACKGROUND: It is known that interleukin-2 (IL-2) activated cytotoxic lymphocytes require a cell-cell contact to exert their anticancer action. Therefore, the pronounced fibrosis that generally characterizes the neoplastic mass could counteract the action of cytotoxic lymphocytes. Some preliminary studies have shown that progesterone and its analogs may inhibit fibroblast proliferation. On the basis of such evidence, we have designed a clinical study with or without the progestational agent medroxyprogesterone acetate (MPA) in metastatic renal cancer patients in maintenance therapy with IL-2 following response or stable disease (SD) after two cycles of IL-2 subcutaneous immunotherapy, in an attempt to evaluate the influence of MPA on free-from progression (FPP) period. METHODS: The study included 30 consecutive patients who were randomized to receive IL-2 alone (3 million IU twice/day for 5 days/month subcutaneously) or IL-2 plus low-dose MPA (500 mg orally one day/week) without interruption until disease progression. RESULTS: A FPP period longer than 1 year was obtained in 8/14 patients treated with IL-2 plus MPA and in only 3/16 patients treated with IL-2 alone. The difference was statistically significant. On the contrary, no significant difference was seen in the mean number of lymphocytes and eosinophils, which was evaluated monthly. Finally, no hyperglycemic or thromboembolic complications occurred in patients concomitantly treated with MPA. CONCLUSIONS: This preliminary study would suggest that the concomitant administration of low-dose MPA may prolong the FFP period in metastatic renal cancer patients under maintenance therapy with IL-2. A longer follow-up will be required to evaluate the influence of MPA on overall survival.

Adult↗

PubMed1993

Radioendocrine therapy of brain tumors with the long acting opioid antagonist naltrexone in association with radiotherapy.

AIMS AND BACKGROUND: Malignant gliomas remain untreatable as the different therapeutic combinations are generally only palliative. Recent experimental evidence suggests that endogenous opioid peptides are involved in brain tumor growth. The aim of the present study was to evaluate the effect on survival of concomitant administration of the long-acting opioid antagonist naltrexone (NTX) in patients with malignant astrocytomas treated with radiotherapy (RT). METHODS: 21 patients with high grade malignant gliomas were randomized to receive RT alone or RT plus NTX. The dose of RT was 60 Gy. NTX was given orally at a dose of 100 mg every other day without interruption until disease progression. RESULTS: The objective tumor regression rate in patients treated with RT plus NTX was higher than that of those treated with RT alone but not significantly so. On the contrary, the percentage of survivals at 1 year was significantly higher in patients treated with RT plus NTX than in those treated with RT alone (5/10 vs 1/11, P < 0.05). NTX therapy was substantially well tolerated in most patients. CONCLUSIONS: The finding of longer survival in brain tumor patients treated with RT plus NTX than in those who received RT alone suggests in vivo involvement of endogenous opioid peptides in regulating the growth of malignant astrocytomas.

Adult↗

PubMed1993

Prevention by L-carnitine of interleukin-2 related cardiac toxicity during cancer immunotherapy.

AIMS AND BACKGROUND: Cardiac toxicity has been observed during IL-2 cancer immunotherapy. Because of its trophic action on the myocardial tissue, the use of L-carnitine has been evaluated during IL-2 therapy in advanced cancer patients with clinically important cardiac diseases. METHODS: The study included 30 cancer patients, who were randomized to treatment with IL-2 alone or IL-2 plus L-carnitine (1000 mg/day orally). IL-2 was injected subcutaneously at a daily dose of 6 million IU for 5 days/week for 4-6 weeks. RESULTS: The percentage of cardiac complications was significantly lower in patients concomitantly treated with L-carnitine than those receiving IL-2 alone (0/15 vs 4/15; P < 0.05), whereas no difference was seen in mean creatine phosphokinase levels on study. CONCLUSIONS: The results would suggest that L-carnitine may be used successfully to prevent cardiac complications during IL-2 immunotherapy in cancer patients with clinically relevant cardiac disorders. Since cardiac metabolism depends mainly on fatty acid oxidation, the stimulatory role of L-carnitine on fatty acid oxidation could explain at least in part its ability to prevent heart disturbances in response to IL-2 administration.

Adult↗