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Biomedical subjects

A Ardizzoia

Publications and source records attributed to A Ardizzoia.

At least 73 records · Page 4Linked to original sources
PubMedDate not supplied

Efficacy of cancer chemotherapy in relation to the pretreatment number of lymphocytes in patients with metastatic solid tumors.

The evidence of lymphocytopenia has been demonstrated to predict a poor prognosis in terms of survival in advanced cancer patients. This finding is not surprising because of the fundamental role of lymphocytes in mediating tumor cell destruction. Despite the importance of lymphocytes in the pathogenesis of cancer, there are only few data about the profile and the function of lymphocytes during the various antitumor therapies, and in particular the relation between lymphocyte pretreatment number and response to chemotherapy remains to be established. The present study was performed to evaluate whether the evidence of lymphocytopenia before the onset of treatment may influence the efficacy of chemotherapy in metastatic cancer patients affected by the most frequent tumor types. The study included 183 patients (lung cancer: 89; colorectal cancer: 63; breast cancer: 31), 95 of whom had been previously treated with chemotherapy. The chemotherapeutic regimens consisted of oxaliplatin plus 5-fluorouracil and folates in untreated colorectal cancer, weekly irinotecan in pretreated colorectal cancer, cisplatin plus gemcitabine or etoposide in untreated lung cancer, weekly vinorelbine in pretreated lung cancer, and taxotere in breast cancer patients who had been previously treated with anthracyclines. Lymphocyte count was considered to be abnormally low for values below 1500/mm3. Lymphocytopenia was found in 79/183 (43%) patients, without any significant differences in relation to tumor histology. A complete response (CR) was achieved in 6/104 patients with a normal lymphocyte count and in none of the 79 lymphocytopenic patients. A partial response (PR) was obtained in 39 patients with a normal lymphocyte count and in only eight patients with a low lymphocyte count prior to therapy. Therefore, irrespective of the type of chemotherapy, the objective tumor response rate (CR + PR) in lymphocytopenic patients was significantly lower than in patients with normal pretreatment lymphocyte counts (8/79 vs 45/104; p < 0.001). This study shows that the evidence of lymphocytopenia prior to chemotherapy is associated with a lower efficacy of treatment in terms of objective tumor regression rates in patients with metastatic solid tumors, and suggests that the action of chemotherapy may depend at least in part on an interaction with the antitumor immunity. Pretreatment lymphocyte count may represent a new, simple biological marker to be taken into consideration by oncologists in the chemotherapeutic treatment of metastatic cancer.

Adult↗
PubMedDate not supplied

Endocrine effects of human recombinant interleukin-3 in cancer patients.

It is known that several cytokines can exert hormonal effects. At present, no data are available about the possible influence of IL-3 on the endocrine system. In order to investigate the endocrine effects of IL-3 in humans, we have evaluated serum levels of cortisol, beta-endorphin, GH, PRL, FSH, LH, TSH and melatonin in response to intravenous injection of IL-3 at a dose of 1 mcg/kg b.w. at 6.00 p.m. The study was performed in 5 non-small cell lung cancer patients. GH increased significantly in response to IL-3. PRL showed a progressive decrease after IL-3 injection, but its variations were not statistically significant. All other hormones, including cortisol, were not affected by IL-3. This preliminary study shows that IL-3 may exert endocrine effects in humans, which would seem at variance with previously reported results on most other cytokines.

Biomarkers, Tumor↗
PubMedDate not supplied

Stimulation of IL-12 secretion by GM-CSF in advanced cancer patients.

In addition to its efficacy in the treatment of chemotherapy-induced neutropenia, recent evidence would suggest that GM-CSF may have immunomodulatory effects on anticancer immunity. In particular, GM-CSF has been proven to promote dendritic cell maturation, with following potential stimulation of the anticancer cytokine, IL-12. Unfortunately, at present there are only few and controversial results on GM-CSF effects on IL-12 secretion in cancer patients. This preliminary study was performed to evaluate IL-12 response to an acute injection of GM-CSF in human neoplasms. The study included 20 advanced cancer patients, who received GM-CSF for chemotherapy-induced neutropenia. GM-CSF was injected at 3 micrograms/kg at 8.00 A.M., and venous blood samples were drawn before GM-CSF, and at 4, 8, 12 and 24 hours after its injection. Serum levels of IL-12 were measured by an enzyme immunoassay. High basal levels of IL-12 were seen in 8/20 patients. In patients with abnormally high pretreatment levels of IL-12, no significant change occurred in IL-12 mean serum concentration after GM-CSF administration. In contrast, patients with normal baseline levels of IL-12 showed a significant increase in IL-12 mean concentrations in response to GM-CSF, with a peak after 12 hours. This preliminary study seems to show that GM-CSF may acutely stimulate IL-12 secretion in cancer patients. Further studies are required to evaluate the effects of chronic GM-CSF administration, and the impact of GM-CSF-induced secretion of IL-12 on the efficacy of the immunotherapies of cancer with cytokines, such as IL-2. In any case, this study would justify further research in the emerging oncological applications of GM-CSF as an immunomodulatory agent on host anticancer defenses.

Adjuvants, Immunologic↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

A clinical study of taxotere versus taxotere plus the antiprolactinemic agent bromocriptine in metastatic breast cancer pretreated with anthracyclines.

Prolactin (PRL) constitutes a growth factor for breast cancer cell proliferation and abnormally elevated blood concentrations of PRL are associated with poor prognosis and reduced efficacy of antitumor therapies in metastatic breast carcinoma. It has already been demonstrated that low-dose bromocriptine, an antiprolactinemic long-acting dopaminergic drug, normalizes PRL blood concentrations in metastatic breast cancer patients with abnormally elevated PRL levels. In addition, previous clinical studies have already demonstrated a lower efficacy of chemotherapy with taxotere in metastatic breast cancer, with persistent hyperprolactinemia. We planned a controlled clinical study to evaluate the influence of a concomitant administration of the antiprolactinemic drug bromocriptine on the efficacy of chemotherapy with taxotere, in metastatic breast cancer patients progressing after chemotherapeutic combinations containing anthracyclines. The study included 30 randomized consecutive patients treated with taxotere alone or taxotere plus bromocriptine. Taxotere was given I.V. at 100 mg/m2 every 21 days for 3 cycles. Bromocriptine was given orally at 2.5 mg/day every day until the end of the chemotherapeutic treatment. Bromocriptine therapy induced a significant decline in PRL mean blood concentrations compared to patients treated by chemotherapy alone. No complete response was obtained. A partial response (PR) occurred in 5 out of 14 (36%) patients treated with taxotere plus bromocriptine and in only 2 out of 16 (13%) patients treated with taxotere alone. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with taxotere alone and in 7 out of 14 patients concomitantly treated with bromocriptine. Therefore, the percent of non-progressive disease (PR + SD) achieved in patients treated with taxotere plus bromocriptine was significantly higher with respect to that found in patients treated with taxotere alone (12 out of 14 vs 7 out of 16, p < 0.025). This preliminary clinical study would suggest that the inhibition of PRL secretion by antiprolactinemic drugs such as bromocriptine may enhance the efficacy of chemotherapy for metastatic breast cancer.

Aged↗
PubMedDate not supplied

Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations.

Recent advances in immunobiological knowledge have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones. In particular, the pineal neurohormone melatonin (MLT), which is able to exert both antioxidant and immunomodulating effects, has been proven to enhance the efficacy of various chemotherapeutic drugs, namely cisplatin, anthracyclines and 5-fluorouracil, whereas at present there are no data about its possible influence on cytotoxic drugs effective in the treatment of colon cancer other than 5-fluorouracil, such as irinotecan (CPT-11). The present study was performed to evaluate the influence of a concomitant administration of MLT on CPT-11 therapeutic activity in metastatic colorectal cancer. The study included 30 metastatic colorectal cancer patients progressing after at least one previous chemotherapeutic line containing 5-fluorouracil, who were randomized to be treated with CPT-11 alone or CPT-11 plus MLT. According to a weekly low-dose schedule, CPT-11 was given i.v. at 125 mg/m2/week for 9 consecutive weeks. MLT was administered orally at 20 mg/day during the dark period of the day. No complete response was observed. A partial response (PR) was achieved in 2 out of 16 patients treated with CPT-11 alone and in 5 out of 14 patients concomitantly treated with MLT. Moreover, a stable disease (SD) was obtained in 5 out of 16 patients treated with CPT-11 alone and in 7 out of 14 patients treated with CPT-11 plus MLT. Therefore, the percent of disease-control achieved in patients concomitantly treated with MLT was significantly higher than that observed in those treated with chemotherapy alone (12 out of 14 vs 7 out of 16, p < 0.05). The only important toxicity was diarrhoea grade 3-4, which occurred in 6 out of 16 patients treated with CPT-11 alone and in 4 out of 14 patients treated with CPT-11 plus MLT, which required a 50% dose reduction. However, taken together, patients treated with CPT-11 at 50% of the planned dose showed a percent of disease control comparable to that achieved in patients who had no dose reduction (6 out of 10 vs 13 out of 20). This preliminary study shows that the efficacy of weekly low-dose CPT-11 in pretreated metastatic colorectal cancer patients may be enhanced by a concomitant daily administration of the pineal hormone MLT, according to the results previously reported for other chemotherapeutic agents. Moreover, since the dose reduction of CPT-11 does not influence its efficacy, the dose of CPT-11 for successive studies might be not greater than 70 mg/m2.

Adjuvants, Immunologic↗
PubMedDate not supplied

Immunological effects of a single evening subcutaneous injection of low-dose interleukin-2 in association with the pineal hormone melatonin in advanced cancer patients.

Recent experiments have shown that a great variety of neurohormones can interact with IL-2 in the modulation of host antitumor immune response. On the basis of these data, a study was started to evaluate the effect of the pineal hormone melatonin (MLT) on IL-2-induced immune changes in cancer. The study included 30 advanced cancer patients. They were randomized to be treated with IL-2 at a dose of 3 million IU subcutaneously twice/daily (8.00 a.m. and 8.00 p.m.) for 6 days/week for 4 weeks, with IL-2 once/daily in the evening, with IL-2 once/daily plus MLT at 10 or at 50 mg/day. MLT was given orally at 8.00 p.m. Both IL-2 given twice daily and IL-2 given once daily and IL-2 given once daily in association with MTL induced a significant increase in mean number of lymphocytes, T lymphocytes, NK cells, CD25-positive cells and eosinophils, whereas the single administration of IL-2 alone was unable to determine a significant rise in the mean number of immune cells. Soluble IL-2 receptor and neopterin increase was significantly higher during IL-2 given twice/daily than during IL-2 plus MLT, while no difference was seen in TNF rise. This study would suggest that a single daily injection of low-dose IL-2 is able to efficiently activate the lymphocyte proliferation in cancer patients when it is given in association with the pineal hormone MLT.

Adult↗
PubMedDate not supplied

Effects of granulocyte-macrophage colony stimulating factor on cortisol, growth hormone, prolactin and melatonin in cancer patients (short communication).

Several interleukins and interferons have been proven to induce endocrine effects. On the contrary, only few data are available about the possible hormonal activity of hemopoietic growth factors. This study was carried out to evaluate the endocrine influence of GM-CSF in humans. The study included nine head and neck cancer patients, evaluated in basal conditions and after an acute subcutaneous injection of GM-CSF at a dose of 3 mcg/kg b.w., by determining serum levels of cortisol, growth hormone (GH), prolactin (PRL) and melatonin. Both cortisol and GH significantly increased in response to GM-CSF, while PRL, and melatonin were not influenced. This preliminary study shows that hemopoietic growth factors, as well as interleukins, may also play endocrine effects in humans.

Adult↗
PubMedDate not supplied

Inhibitory effect of interleukin-3 on interleukin-2-induced cortisol release in the immunotherapy of cancer.

The stimulatory effect of IL-2 on cortisol rise represents an undesirable biological event during IL-2 cancer immunotherapy. At present, no cytokine has been proven to be able to counteract IL-2-induced cortisol increase. This study was carried out to evaluate the influence of IL-3 on IL-2 stimulation of cortisol secretion. Five lung cancer patients were investigated after IL-2 (3 x 10(6) IU s.c.), after IL-3 (1 mcg/kg b.w. i.v.) and after IL-3 plus IL-2, by administering IL-3 two hours before IL-2 injection. IL-2 significantly stimulated cortisol secretion. IL-3 alone had no effect on cortisol levels. The pretreatment with IL-3 completely neutralizes IL-2-induced cortisol release. These preliminary results would suggest that IL-3 may be associated with IL-2 during cancer immunotherapy to modulate the effect of IL-2 on the endocrine system.

Carcinoma, Non-Small-Cell Lung↗
PubMedDate not supplied

Tumor necrosis factor in solid tumors: increased blood levels in the metastatic disease.

TNF, a cytokine produced by macrophages, is able either to exert an antitumor activity, or to determine severe clinical complications, such as cachexia and septic shock. Increased blood levels of TNF have been described in cancer patients. The present study was performed to better define TNF secretion in patients with solid tumors. The study included 48 cancer patients (lung cancer: 22; colon cancer: 11; breast cancer: 10; renal cancer: 5), and among them 27 showed distant organ metastases. TNF serum levels were measured by IRMA method. The control group comprised 40 healthy subjects. TNF levels were also evaluated in relation to those of SIL-2R, whose increase seems to be associated with an unfavorable prognosis in cancer. High levels of TNF were seen in 27/48 (56%) patients. Mean levels of TNF were significantly higher in cancer patients than in controls. Moreover, within the cancer group, TNF mean values were significantly higher in metastatic patients than in those without metastases; the highest levels were observed in patients with visceral lesions as dominant metastasis sites. Finally, patients with high TNF concentrations showed significantly higher mean levels of SIL-2R than those with normal values. This study shows that the neoplastic metastatic disease is associated with an exaggerated TNF secretion.

Adult↗
PubMedDate not supplied

Enhancement of the efficacy of weekly low-dose taxotere by the long acting anti-prolactinemic drug cabergoline in pretreated metastatic breast cancer.

In view of its potential action as a growth factor, the evidence of abnormally high blood levels of prolactin (PRL) is associated with a poor prognosis in metastatic breast cancer. Moreover, metastatic breast cancer-related hyperprolactinemia has proven to counteract the efficacy of cancer chemotherapy. The negative influence of high blood levels of PRL on the efficacy of chemotherapy in metastatic breast cancer has been confirmed by previous preliminary studies, showing that the concomitant administration of the anti-prolactinemic dopaminergic agent bromocriptine may enhance the therapeutic effect of chemotherapy. However, the clinical use of bromocriptine is limited by its short duration and gastrointestinal toxicity. Therefore, new anti-prolactinemic drugs, characterized by less toxicity and a longer duration of activity, such as Cabergoline (CBG), could be more appropriated to control PRL secretion in breast cancer. On this basis, a study was planned to evaluate the efficacy and tolerability of a concomitant administration of CBG with weekly low-dose Taxotere (TXT) in pretreated metastatic breast cancer under chemotherapy. The study group comprised 70 metastatic breast cancer patients (females), pretreated with at least one previous chemotherapeutic line containing anthracyclines, who were randomized to be treated with TXT alone or TXT plus CBG. TXT 25 mg/m2 was given i.v. at weekly intervals for at least 9 consecutive cycles. CBG was given orally at 0.5 mg once per week. Abnormally high pre-treatment levels of PRL were seen in 24/70 (34%) patients, 11 of whom were treated with TXT plus CBG, whereas the other 13 received TXT alone. CBG induced a complete normalization of the PRL levels in all patients within the first two weeks of therapy, whereas no normalization of PRL occurred spontaneously in patients treated with chemotherapy alone. The objective tumor regression rate was significantly higher in patients concomitantly treated with CBG than in those who received chemotherapy alone (31/34 vs 13/36, p < 0.05), and this difference was particularly evident in patients with high PRL levels prior to therapy (6/11 vs 2/13). No CBG-related toxicity occurred. On the contrary, chemotherapy-induced asthenia was significantly lower in patients concomitantly treated with CBG (5/34 vs 11/36, p < 0.05). This study shows that the chemoneuroendocrine therapy of weekly low-dose TXT plus the anti-prolactinemic drug CBG is a new, effective and well-tolerated therapy for metastatic breast cancer. It may also be recommended in heavily pretreated patients or in those with poor clinical status.

Adult↗
PubMedDate not supplied

Modulation of interleukin-2-induced macrophage activation in cancer patients by the pineal hormone melatonin.

The concomitant induction of immunosuppressive events, at least in part mediated by macrophages, would represent one of the mechanisms responsible for the lower activity of IL-2 in vivo than in vitro. Since macrophages have recently appeared to be under neuroendocrine control, the present study was carried out to evaluate the effect of the pineal neurohormone MLT on IL-2-induced macrophage activation during cancer immunotherapy, by determining serum levels of neopterin, which is a specific marker of macrophage activity. The study included 21 advanced cancer patients (lung cancer: 12; renal cancer: 9), 10 of whom received IL-2 subcutaneous therapy alone (1.8 x 10(6) IU/m2 twice daily), or IL-2 plus MLT (10 mg/day orally at 8.00 P.M.). Neopterin levels increased in all patients during IL-2 immunotherapy, but neopterin mean peak was significantly higher in patients treated with IL-2 alone than in those who received IL-2 plus MLT. This preliminary study would suggest the possible use of neurohormones to modulate host antitumor immune response during cancer immunotherapy with IL-2.

Adult↗
PubMedDate not supplied

Weekly epirubicin plus low-dose interleukin-2 subcutaneous therapy in breast cancer: preliminary immunobiological results.

Experimental studies have shown that IL-2 may antagonize chemotherapy-induced lymphocytopenia. On this basis, we have evaluated the influence of low-dose IL-2 on lymphocyte and NK cell numbers in cancer patients treated with the anthracycline drug, epirubicin. The study included 7 metastatic breast cancer women treated with epirubicin at a dose of 25 mg/m2 i.v. weekly. IL-2 was given subcutaneously at 3 million IU/day for 6 days/week. Venous blood samples were drawn at weekly intervals, and the results were compared to those seen in 14 patients treated with epirubicin alone. Lymphocyte mean number observed on treatment was higher in patients concomitantly treated with IL-2 than in those receiving epirubicin alone, without, however, significant differences. In addition, NK cell mean number was significantly higher in patients receiving IL-2 than in those treated with epirubicin alone. These preliminary results would suggest that IL-2 may antagonize lymphocyte and NK cell declines during cancer chemotherapy with anthacyclines. Further studies will be required to confirm these results and to establish their possible influence on chemotherapy-induced tumor regressions.

Adult↗
PubMedDate not supplied

Cancer immunotherapy with low-dose interleukin-2 subcutaneous administration: potential efficacy in most solid tumor histotypes by a concomitant treatment with the pineal hormone melatonin.

The antitumor efficacy of IL-2 is limited to renal cancer and melanoma. Several cytokines have been associated with IL-2 in an attempt to improve its activity, without, however, any clear benefit. Recent experimental and clinical studies have suggested the possibility to manipulate the host biological response by immunomodulating neurohormones, such as the pineal hormone melatonin (MLT). On the bases of these considerations, we have designed a neuroimmunotherapeutic protocol with low-dose IL-2 subcutaneous therapy (3 million IU/day for 6 days/week for 4 weeks) plus MLT (40 mg/day orally, starting 7 days before IL-2) in advanced solid neoplasms other than renal cancer and melanoma, which are generally resistant to IL-2 alone. The study included 82 patients, 72 of whom showed distant organ metastases. Tumor histotypes were, as follows: non-small cell lung cancer: 19; hepatocarcinoma: 16; colon cancer: 15; gastric cancer: 11; cancer of pancreas: 11; breast cancer: 6; miscellaneous: 4. Objective tumor regression were achieved in 17/82 (21%) patients, consisting of CR in 4 (liver: 2; pancreas: 1; stomach: 1) and PR in 13 (lung: 4; liver: 4; stomach: 2; pancreas: 1; breast: 1; colon: 1). The median duration of response was 8+ months. A stabilization of disease was obtained in 30 patients, while the other 35 patients progressed. The lack of progression was associated with a significantly higher increase in lymphocyte and eosinophil mean number and with a significantly lower increase in neopterin mean levels. The treatment was well tolerated in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗