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Biomedical subjects

G Tancini

Publications and source records attributed to G Tancini.

At least 19 recordsLinked to original sources
PubMed1992

Neuroimmunotherapy with subcutaneous low-dose interleukin-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma.

On the basis of our previous preliminary data which showed that the pineal hormone melatonin (MLT) may potentiate IL-2 activity and reduce the dose of IL-2 required to determine an effective host antitumor response, we performed a clinical study with low-dose IL-2 given once/day subcutaneously (3 million IU/day for 6 days/week for 4 weeks) in association with MLT (50 mg/day orally at 8.00 p.m. every day) as a second-line therapy in metastatic colorectal cancer patients pretreated with 5-fluorouracil. Evaluable patients were 13/14, and most of them showed disseminated liver metastases. No objective tumor regression was seen. A stabilization of disease was achieved in 4/13 patients (median duration 5+ months), and the other 9 patients progressed. Mean number of lymphocytes and eosinophils significantly increased during the treatment. Moreover, the mean increase in lymphocyte number was significantly higher in patients with stable disease than in those with progressive disease, whereas there was no difference as regards eosinophils. Serum levels of neopterin and tumor necrosis factor (TNF) significantly increased during therapy, and TNF increase was correlated to the side effects rather than to the control of cancer development. This study shows that neuroimmunotherapy with low-dose interleukin-2 and MLT, even though capable of determining an evident expansion of immune cells involved in host antitumor response, does not seem to be effective in terms of tumor regression in metastatic colon cancer patients pretreated with 5-fluorouracil.

Adult↗
PubMed1992

Weekly doxorubicin chemotherapy for breast cancer in pregnancy. A case report.

The simultaneous occurrence of breast cancer and pregnancy is rare. Little data are available about cytostatic treatment in patients with breast cancer during pregnancy. We report on a 31-year-old woman with a 28-week pregnancy and a T3 N+ Mx breast cancer treated with weekly doxorubicin chemotherapy. This was a well tolerated treatment without toxicity or complications for the mother. A partial response of the tumor was observed after 4 treatment courses. A normal baby was delivered. Doxorubicin and its metabolites were not detected in amniotic fluid collected through amniocentesis. Macroscopic and pathologic examinations of the placenta were normal. Although larger experiences are needed, weekly doxorubicin seems to yield satisfactory results without additional risks of fetal distress or malformations when given in women during the second and third trimester of pregnancy.

Adult↗
PubMed1992

Postoperative increase in soluble interleukin-2 receptor serum levels as predictor for early recurrence in non-small cell lung carcinoma.

It is known that interleukin-2 (IL-2) plays an important role in the activation of host antitumor immune response. In addition to IL-2 cell surface receptor, a soluble form of IL-2 receptor (SIL-2R) may be released in the blood and potentially be involved in the regulation of IL-2 availability. High SIL-2R levels have been found in patients with lung cancer. The current study evaluated the influence of changes in SIL-2R serum levels during the perioperative period on early relapse rate in patients with operable non-small cell lung cancer. The study included 60 patients (epidermoid carcinoma, 33; adenocarcinoma, 27). Serum levels of SIL-2R were measured with an enzyme immunoassay before surgery and 7 and 30 days after surgery. A surgery-induced increase in SIL-2R levels was seen 7 days after surgery in 38 of 60 patients. On the 30th day after surgery, SIL-2R values were lower than the preoperative values in 32 patients (Group A) or still greater in the other 28 patients (Group B). After a median follow-up of 10 months, relapse occurred in 19 of 60 patients. The relapse rate was significantly higher in Group B than in Group A patients (16 of 28 versus 3 of 32, respectively; P less than 0.001). This difference also was significant in relation to histotype and node status. This study shows that the persistence of increased SIL-2R levels in the postoperative period is associated with a higher early relapse rate in patients with operable non-small cell lung cancer. The impact of SIL-2R levels on relapse suggests that host immune defenses may influence the clinical course of patients with lung cancer. Therefore, the evaluation of SIL-2R in the perioperative period may represent a new prognostic biologic factor in operable non-small cell lung cancer.

Aged↗
PubMed1992

Intracavitary administration of interleukin-2 as palliative therapy for neoplastic effusions.

Cytokines have recently appeared to be effective in the palliative therapy of neoplastic effusions. The present study was carried out to evaluate the efficacy and the tolerability of an intracavitary injection of IL-2 in patients with neoplastic effusion due to solid tumors. The study included 14 patients with cytologically positive effusion (pleura, 11; peritoneum, 2; pericardium, 1). Tumor histotypes were: mesothelioma, 5; non-small cell lung cancer, 3; breast cancer, 2; ovarian cancer, 2; cervix carcinoma, 1; unknown primary tumor, 1. The efficacy was evaluated according to the criteria of Paladine et al. (Cancer 38: 1903, 1976). An objective response was achieved in 10/14 (71%) patients (4 CR, 6 PR), with a median duration of 4 months (range, 2-8). No important toxicity was seen. This preliminary study showed that low dose IL-2 given intracavitarily is an effective and well-tolerated therapy in patients with neoplastic effusions.

Adult↗
PubMed1992

Second line therapy with low-dose subcutaneous interleukin-2 alone in advanced renal cancer patients resistant to interferon-alpha.

Interleukin-2 (IL-2), given subcutaneously with interferon-alpha, induces clinical results similar to those achieved with intravenous administration in advanced renal cancer but with lower toxicity. This study was performed to investigate the efficacy of IL-2 subcutaneous therapy alone in advanced renal cancer patients pretreated with interferon-2 alpha. The study included 13 evaluable patients, 6 of whom had visceral metastasis sites. The cycle consisted of IL-2 at 9 x 10(6) IU/m2 twice daily for 2 days, followed by 1.8 x 10(6) IU/m2 every 12 h for 5 days/week for 6 weeks. Clinical responses were: partial response: 4(31%); stable disease: 7(54%), progressive disease: 2(15%). The median duration of response was 9+ months (range 6(+)-12+). Toxicity was low in all patients, and in particular no important cardiovascular side-effect was seen. The results of this study show that IL-2 subcutaneous therapy alone is an effective and well tolerated treatment in advanced renal cancer patients progressed under interferon-alpha therapy.

Adenocarcinoma↗
PubMed1992

Biological and clinical results of a neuroimmunotherapy with interleukin-2 and the pineal hormone melatonin as a first line treatment in advanced non-small cell lung cancer.

The metastatic non-small cell lung cancer (NSCLC) still remains an untreatable disease, and the role played by chemotherapy has yet to be defined. The new immunotherapeutic strategies, such as interferon and IL-2, seem to be also less effective, since they generally determine only a stabilisation of disease. On the basis of previous experimental results suggesting a synergistic action between IL-2 and the pineal neurohormone melatonin (MLT), a study was started to evaluate the clinical efficacy and toxicity of a neuroimmunotherapeutic combination consisting of IL-2 plus MLT as a first line therapy in metastatic NSCLC. The study included 20 patients (adenocarcinoma: 10; epidermoid cell carcinoma: 7; large cell carcinoma: 3). MLT was given orally at a dose of 10 mg day-1 at 8.00 pm every day, starting 7 days before the onset of IL-2 administration. IL-2 was given subcutaneously at a dose of 3 x 10(6) IU m-2 every 12 h for 5 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In responder patients or in those with stable disease, a second cycle was given after a rest-period of 21 days. A partial response was achieved in 4/20 (20%) patients. Ten other patients had a stable disease (50%), whereas the last six patients progressed. Toxicity was low in all cases. This study shows that the neuroimmunotherapeutic therapy with IL-2 and the pineal hormone MLT may represent a new effective and well tolerated treatment in metastatic NSCLC, with results comparable to those obtained with chemotherapy, but with an apparent lower biological toxicity.

Biopterins↗
PubMed1992

Effects of a preoperative therapy with interleukin-2 on surgery-induced lymphocytopenia in cancer patients.

It is known that major surgery may determine immunosuppression. This side effect might have a prognostic significance particularly in cancer patients, in whom the decrease in host defenses during the postoperative period could promote the proliferation of possible micrometastases. Since antitumor immune response is an IL-2-dependent phenomenon, a study was started to evaluate the effects of a preoperative injection of IL-2 on surgery-induced immune changes in cancer patients. The study included 12 colon cancer patients, treated subcutaneously with IL-2 at a dose of 9 x 10(6) IU/m2 twice daily for 3 consecutive days before surgery. Patients underwent surgery within 36 h from IL-2 interruption. The results were compared to those found in a control group of 18 colon cancer patients. Mean number of lymphocytes, T lymphocytes and NK cells significantly decreased after surgery in control patients; on the contrary, no postoperative decrease in immune cells was seen in IL-2 group. No anesthesiologic or surgical complication was seen in patients pretreated with IL-2 before surgery. This preliminary study would suggest that a preoperative therapy with IL-2 is an effective and well tolerated medical approach to neutralize surgery-induced immunosuppression in cancer patients.

Adult↗
PubMed1992

Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin.

At present, there is no effective medical therapy in metastatic nonsmall cell (NSC) lung cancer patients who progressed under a first-line chemotherapy containing cisplatin. Since recent data have demonstrated the antineoplastic properties and the lack of toxicity of the pineal hormone melatonin (MLT), a randomized study was designed to evaluate the influence of an MLT treatment (10 mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients, who did not respond to a first-line chemotherapy containing cisplatin. The study includes 63 consecutive metastatic NSC lung cancer patients, who were randomized to receive MLT (n = 31) or supportive care alone (n = 32). The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care. No drug-related toxicity was seen in patients treated with MLT, who, on the contrary, showed a significant improvement in performance status. This randomized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSC lung cancer patients who progressed under a first-line chemotherapy with cisplatin, for whom no other effective therapy is available up to now.

Adult↗
PubMed1992

Modulation of macrophage response to interleukin-2 immunotherapy by interleukin-3 in cancer patients.

It has been observed that neopterin, a specific marker of macrophage activation, increases during cancer immunotherapy with IL-2, and this effect is mediated by interferons produced by IL-2-stimulated lymphocytes. Moreover, our previous studies have shown that neopterin rise during IL-2 immunotherapy is associated with an enhanced release of soluble IL-2 receptor (SIL-2R), which may suppress IL-2-dependent immune functions. This finding would suggest that neopterin increase may be related to the generation of suppressive events, which occur during IL-2 immunotherapy. On the basis of the documented modulatory effect of IL-3 on macrophage functions, we have evaluated the influence of IL-3 on neopterin secretion during IL-2 immunotherapy. The study was performed in advanced lung cancer patients. We have investigated 9 immunotherapeutic courses consisting of IL-2 (6M IU/day s.c. for 5 days/week for 3 weeks) plus IL-3 (1 microgram/(kg x day) i.v. for 14 days, starting 7 days before IL-2). The results were compared to those found during 18 courses with IL-2 alone. Mean neopterin levels increased significantly during IL-2 alone, but not in response to IL-3 plus IL-2. SIL-2R rise was significantly higher during IL-2 than during IL-3 plus IL-2. Mean numbers of NK cells and activated lymphocytes increased significantly in both groups of patients, but were significantly lower at the end of the treatment in patients receiving IL-2 alone than in those treated with IL-3 plus IL-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

Neuroendocrine effects of subcutaneous interleukin-2 injection in cancer patients.

Intravenous interleukin-2 (IL-2) administration has been shown to influence several hormonal secretions. The present study was carried out to investigate the endocrine effects of subcutaneous therapy with IL-2. Six patients with advanced renal cancer were studied. They were treated subcutaneously with IL-2 according to the schedule proposed by Atzpodien et al. Venous blood samples were collected at O-time and 1, 8 and 12 hours after the first IL-2 pulse of 9 X 10(6) IU/m2 at 8.00 a.m.; on a separate occasion, samples were collected during a saline infusion only. In each blood sample, serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and the pineal hormone melatonin were measured by RIA. Both cortisol and beta-endorphin significantly increased after IL-2 injection. GH rose but not to a significant extent. PRL, FSH, LH and TSH did not change after IL-2. Finally, melatonin levels markedly decreased after IL-2 injection in the only 2 patients with elevated concentrations of this hormone before the start of immunotherapy. These results suggest that the endocrine effects of subcutaneous IL-2 therapy are similar to those previously described with intravenous administration.

Adult↗
PubMed1991

Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response.

Mitoxantrone (DHAD), an anthracenedione with antineoplastic properties similar to doxorubicin, was tested for therapeutic efficacy and for immunomodulating action on lymphocyte subsets in 16 metastatic breast cancer patients, 12 of whom had been previously treated with chemotherapy. DHAD was given intravenously at a dose of 14 mg/m2 every 21 days. To evaluate total T lymphocytes (CD3), T helper (CD4), and T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio, venous blood samples were drawn before and after the first DHAD cycle. Moreover, in 8/16 patients, B lymphocytes (CD20), T suppressor cells (CD8+/CD57+), T cytotoxic cells (CD8+/CD57-), NK (CD16) and IL-2 receptor-expressing cells (CD25) were also measured at the same time. An objective tumor response was achieved in 5/16 (31%) patients and the response rate was significantly higher in patients pretreated with hormone therapy alone than in those pretreated with chemotherapy. No relation was found between clinical response and changes in the CD4/CD8 ratio. Neither the mean number nor the percentage of CD3, CDA and CD8 cells observed after DHAD were significantly different with respect to those seen before. In contrast, the mean number of T suppressor cells, B lymphocytes and CD25-positive cells was significantly lower after than before DHAD administration, whereas no difference was seen in NK cells. These results confirm in humans the immunomodulating properties of DHAD previously described in experimental conditions. However, the DHAD-induced changes in lymphocyte subsets do not seem to be related to the clinical response in breast cancer.

Adult↗
PubMed1991

Effect of antitumor surgery on soluble interleukin-2 receptor serum levels.

Surgically induced immunosuppression may play a role in cancer, because of the possible existence of micrometastases at the time of surgical removal of tumors. Antitumor immune reactions are mediated by interleukin-2 (IL-2). IL-2 acts on a specific IL-2 cell surface receptor; moreover, a soluble form of IL-2 receptor (sIL-2R) can be released in the blood. This study was carried out to evaluate the effect of surgery on sIL-2R serum levels in patients with operable solid tumors. A total of 48 patients with cancer and 11 controls who underwent major surgery for non-neoplastic disease were evaluated before and 7 days after surgery. Serum mean levels of sIL-2R were significantly higher after than before surgery in both the cancer and control groups. No correlation was seen between surgery-induced changes in sIL-2R and in T lymphocyte subsets. Because of its capacity of binding to IL-2, the increased blood concentrations of sIL-2R could reduce the IL-2 availability and negatively affect antitumor immune reactions.

Breast Neoplasms↗
PubMed1991

Increase in soluble interleukin-2 receptor and neopterin serum levels during immunotherapy of cancer with interleukin-2.

Both immunostimulatory and immunosuppressive events would occur during the immunotherapies of cancer, including interleukin 2 (IL-2) therapy. The marked increase in soluble IL-2 receptor (SIL-2R) levels during IL-2 therapy could represent a potentially negative biological effect, because of the receptor's capacity to bind IL-2 and compete for it with IL-2 cell surface receptor. Since it has been observed that macrophages stimulate in vitro the release of SIL-2R, a study was started to evaluate in vivo the role of macrophages in IL-2-induced SIL-2R rise by measuring neopterin, which is a marker of macrophage activity. The study included 9 advanced renal cancer patients, treated subcutaneously with IL-2 at 1.8 x 10(6) IU/m2 twice daily for 5 days/week for 6 weeks. Both SIL-2R and neopterin serum mean levels significantly increased during IL-2 treatment, and the highest concentrations were reached on the second week of therapy. SIL-2R rise was significantly correlated to that of neopterin. This study, by showing a positive correlation between SIL-2R and neopterin rise, would suggest a macrophage involvement in the stimulation of SIL-2R release during IL-2 immunotherapy of cancer.

Adenocarcinoma↗
PubMed1991

Decrease in cholesterol levels during the immunotherapy of cancer with interleukin-2.

IL-2, in addition to its immunomodulating and antitumour properties, induces important systemic actions, including cardiovascular, neuroendocrine and metabolic effects. The present study was carried out to evaluate IL-2 effects on cholesterol metabolism. The study included 14 advanced cancer patients (renal carcinoma: ten; colon carcinoma: four), who received IL-2 subcutaneously at a dose of 1.8 x 10(6) IU ml-2 twice daily for 5 days/week for 6 weeks. Venous blood samples were collected 7 days before, on days 0, 3, 7, 14, 21, 42 of IL-2 therapy, and on days 14 and 28 of the rest-period. IL-2 induced a rapid and evident decrease in cholesterol levels, with a normalisation of its concentrations within 7 days in 10/10 hypercholesterolemic patients. The lowest mean levels of cholesterol were reached within the first 2 weeks; after that they still slowly increased. LDL-/HDL-cholesterol ratio was significantly reduced by IL-2 therapy. Cholesterol fall was associated with a marked increase in conjugated biliary acid levels. Finally, triglyceride values increased during IL-2 therapy, but not in a significant manner. These results, by showing that IL-2 exerts an evident and very rapid cholesterol-lowering activity, would represent a further demonstration of the physiological importance of cytokines in the control of cholesterol metabolism.

Adenocarcinoma↗
PubMed1991

Lower survival in metastatic cancer patients with reduced interleukin-2 blood concentrations. Preliminary report.

It is known that interleukin-2 (IL-2) plays a fundamental role in the generation of immune cells capable of mediating tumor regression. Since IL-2 may be often reduced in patients with disseminated cancer, a pilot study was started to evaluate which relation exists between IL-2 levels and survival in metastatic solid neoplasms. The study included 25 patients with metastatic disease (breast cancer: 12; non-small-cell lung cancer: 13). Serum IL-2 levels were measured by radioimmunoassay on venous blood samples collected before the start of chemotherapy. Breast cancer was treated with weekly epirubicin and lung cancer with cisplatin plus etoposide. Low levels of IL-2 were seen in 10/25 patients. Irrespectively of response to therapy and of dominant metastasis sites, the mean survival time was significantly lower in patients with reduced IL-2 concentrations than in those with normal values. These results would suggest that the evidence of low IL-2 levels negatively influences the clinical course of patients with metastatic solid neoplasms.

Adult↗
PubMed1991

Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies.

The pineal hormone melatonin (MLT) is able to exert an oncostatic action. Its possible use in the treatment of human tumors, however, has not yet been investigated. The present study was carried out to evaluate the effects of MLT in patients with metastatic solid tumors resistant to conventional therapies. The study included 54 patients, most of them were affected by lung cancer or colorectal carcinoma. MLT was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; this induction phase was followed by a maintenance period at a dose of 10 mg orally in responder patients or in those with an improvement in performance status (PS). The clinical response was as follows: 1 partial response (cancer of pancreas), 2 minor responses (colon cancer and hepatocarcinoma) and 21 with stable disease. The remaining 30 patients rapidly progressed within the first 2 months of therapy. An evident improvement in PS was achieved in 18 of 54 (33%) cases. These results, by showing an apparent control of the neoplastic growth and an improvement in the quality of life in a reasonable number of cancer patients for whom no other standard therapy is available, would justify further clinical trials to better define the impact of MLT therapy on the survival and quality of life of untreatable advanced cancer patients.

Adult↗
PubMed1979

Treatment of advanced breast cancer with norethisterone acetate.

The medical records of 84 postmenopausal women treated with oral norethisterone acetate (NTA) for advanced breast cancer were retrospectively analyzed. Treatment was devoid of significant toxicity. Twenty-one patients were not evaluable for treatment response either because of insufficient data or inadequate treatment trial. Complete plus partial response was obtained in 21 (33.3%) of the 63 evaluable patients, with a median duration of 10 months. Disease stabilization was observed in 16 (25.4%) patients for a median duration of 5 months, while 26 patients (41.3%) showed progressive disease while on treatment. The best response was observed in women with dominant soft part disease and an age over 70 (CR+PR 48%). The literature on norethisterone acetate is reviewed and compared with present results. The role of progestational agents in the treatment of advanced mammary carcinoma is discussed.

Age Factors↗