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Biomedical subjects

S Viviani

Publications and source records attributed to S Viviani.

At least 55 records · Page 3Linked to original sources
PubMed1986

A clinical study of the pineal gland activity in oncologic patients.

It has been known for many years that the pineal gland is involved in regulating tumor growth. In order to evaluate the functional activity of the pineal gland in neoplastic diseases, melatonin serum levels and its light/dark rhythm have been determined with the RIA method in patients affected by various forms of tumor. Irrespectively of the type of the tumor and of its localization, existence of two subpopulations has been observed within the oncologic patients, the former with normal levels of melatonin, and the latter with high ones. The light/dark rhythm of melatonin was anomalous in some cases. An evident decrease of serum melatonin values was seen after chemotherapy. It might be interesting to establish whether melatonin levels may conditionate the prognosis of patients with cancer.

Adolescent↗
PubMed1986

CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease.

Starting in February 1980, 58 patients with Hodgkin's disease refractory to both MOPP and ABVD received as third-line chemotherapy a combination of CCNU or lomustine, etoposide, and prednimustine (CEP). Complete response (CR) was achieved in 40% of cases and partial response (PR) in 14%. The median duration of CR was greater than 15 months, and the median survival of complete responders was longer than 24 months. In addition, CEP alternating with ABVD was given to 21 patients refractory to MOPP chemotherapy. In this series, CR was documented in 67% of patients with a median duration of 24+ months and a median survival of 36+ months. Treatment was generally well tolerated, and all acute side effects were reversible. Present findings indicate that CEP is an effective regimen in patients refractory to MOPP and ABVD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Salvage chemotherapy in Hodgkin's disease irradiation failures: superiority of doxorubicin-containing regimens over MOPP.

One hundred and twenty-two consecutive patients with Hodgkin's disease who relapsed after primary curative irradiation were treated with either MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) or a doxorubicin-containing regimen (ADM-Reg). The main pretreatment characteristics were comparable in the two groups. Complete remission was achieved in 74.6% of patients treated with MOPP (44 of 59) and in 90.5% of those given ADM-Reg (57 of 63). No difference was observed in the incidence of complete remission with regard to the type of ADM-Reg utilized [MABOP (mechlorethamine, doxorubicin, bleomycin, vincristine, and prednisone), 92.9%; ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), 95.6%; and MOPP alternated with ABVD, 84.6%]. The superiority of ADM-Reg versus MOPP was also confirmed in the 7-year analysis of freedom from disease progression (73.2% vs 42.2%), relapse-free survival (81.2% vs 54.3%), and overall survival (80.5% vs 44.4%). Thrombocytopenia was less frequently observed with ADM-Reg (30%), particularly following ABVD (13%), compared to MOPP (73%). The lowest incidence of alopecia occurred in patients given MOPP (15%) or MOPP/ABVD (19%). Acute nonlymphoblastic leukemia was observed in patients treated with MOPP (five of 59) and MABOP (one of 14). The observed findings indicate that in patients failing to respond to primary radiotherapy, salvage regimens containing doxorubicin are more effective than MOPP. Furthermore, combinations devoid of procarbazine and alkylating agents (ABVD) or with less intensive administration of these drugs (MOPP/ABVD) were not associated with secondary leukemia.

Adolescent↗
PubMed1985

Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD.

The comparative gonadal toxicity following two equally effective and non-cross-resistant regimens (MOPP and ABVD) was prospectively evaluated in 53 males with Hodgkin's disease. The median age was 29 yr (range 16-45). MOPP produced azoospermia in 28/29 patients (97%) while ABVD induced oligoazoospermia in 13/24 patients (54%). Follicle-stimulating hormone levels were consistently and significantly increased after MOPP while their median value remained within normal range after ABVD. Sperm count was repeated in 34 patients. Recovery of spermatogenesis occurred in 3/21 cases treated with MOPP and in all 13 cases given ABVD. Present findings confirm that the two alkylating agents, mechlorethamine and procarbazine, included in the MOPP regimen cause sterility in most patients while the drugs included in ABVD are not associated with permanent gonadal dysfunction.

Adolescent↗
PubMed1985

Evaluation of semen and pituitary gonadotropin function in men with untreated Hodgkin's disease.

The reproductive capacities of 35 patients with Hodgkin's disease were assessed before treatment by semen evaluation and determination of basal hypothalamic-hypophyseal function and after stimulation with gonadotropin-releasing hormone (GnRH). Sixty-five percent of the patients had asthenozoospermia, 46% had teratozoospermia, and 28% had oligozoospermia. Normal semen was more frequently seen in asymptomatic patients (7 of 18) than in symptomatic patients (2 of 15). All the patients had normal basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and significantly low testosterone (T) levels (P less than 0.01). The FSH response to 100 micrograms of GnRH was normal, but the LH responses were all significantly low, both as delta % (28.4% +/- 18.7% versus 52.4% +/- 25.3%, P less than 0.005) and as peak values (36.7 +/- 20.7 mIU/ml versus 59.4 +/- 26.4 mIU/ml, P less than 0.01). It is believed that abnormal semen is a specific symptom of Hodgkin's disease, secondary to functional insufficiency of the hypothalamic-hypophyseal axis, with a relative decrease in T production.

Adolescent↗
PubMed1985

Prospective randomized trial in advanced malignant melanoma with cis-platinum, vindesine, and etoposide vs. cis-platinum, vindesine, and lomustine.

Thirty-seven consecutive patients with disseminated malignant melanoma and previously untreated with chemotherapy were randomly allocated to receive vindesine, cis-platinum, and etoposide (Regimen A) or vindesine, cis-platinum, and lomustine (Regimen B). In 31 evaluable patients, Regimen A induced an overall response rate of 31% and a complete response rate of 6%; with Regimen B the corresponding findings were 20% and 20%, respectively. The median duration of complete response was 12 months with both regimens and the comparative median total survivals were 8 and 6 months, respectively. In no case was toxicity so severe to require treatment discontinuation, and the major dose-limiting side effect was myelosuppression, especially in the patients treated with Regimen B. Present results confirm once more the limited activity of drugs and regimens presently utilized in the treatment of advanced malignant melanoma.

Adult↗
PubMed1985

Third-line salvage chemotherapy in Hodgkin's disease.

CEP (CCNU, etoposide, and prednimustine) was tested as third-line chemotherapy in 40 patients resistant to both MOPP and ABVD. The observed response rate (complete remission, 35%, and partial remission, 25%) is encouraging. Treatment was generally well tolerated and all acute side effects were reversible.

Adolescent↗
PubMed1985

Phase II study with amsacrines (m-AMSA and m-AMSA lactate) in refractory lymphomas.

A total of 70 patients with malignant lymphomas refractory to one or more chemotherapeutic regimens were treated with iv amsacrines (m-AMSA and m-AMSA lactate). Of 58 evaluable patients, 12 had Hodgkin's disease and 46 had non-Hodgkin's lymphoma. Twenty-nine of the evaluable patients received m-AMSA and 29 received m-AMSA lactate. The amsacrines were recycled every 3 weeks. The doses of m-AMSA were 90-120, 70, and 25-30 mg/m2/day for 3 days, respectively. All patients treated with m-AMSA lactate received a single dose of 225 mg/m2. In Hodgkin's disease, the response rate was 58.3% (one complete response among 12 patients), and in non-Hodgkin's lymphoma, the response rate was 30.4% (six complete responses among 46 patients). The median duration of response was 3 and 5 months, respectively. The response rate was unfavorably affected by the presence of extra-nodal disease and a Karnofsky performance status less than 80. There was no important difference in the incidence and duration of response between m-AMSA and m-AMSA lactate. After vomiting, myelosuppression was the most frequent observed toxic effect. One patient showed an unexpected fatal bone marrow aplasia following the first course of 90 mg/m2. This study indicates that m-AMSA and m-AMSA lactate are active and moderately toxic in previously treated malignant lymphomas. Thus, amsacrines could be effectively incorporated into salvage polydrug regimens.

Adult↗
PubMed1984

Gonadal damage in Hodgkin's disease from cancer chemotherapeutic regimens.

The paper re-emphasizes that intensive prolonged anticancer chemotherapy containing alkylating agents or procarbazine or both produces a high-incidence of gonadal failure, particularly in males. This evidence has been documented mostly in patients with Hodgkin's disease. On the contrary, effective combination regimens, such as ABVD, not including the above mentioned drugs induce a comparatively less and transient germ cell toxicity. In devising chemotherapy for potentially curable neoplastic diseases in young patients efforts should be made to avoid or minimize the potential risk of drug-induced gonadal failure.

Adolescent↗
PubMed1984

A clinicopathologic study in advanced non-Hodgkin's lymphomas treated with sequential non-cross-resistant regimens: comparison of the working formulation with the Rappaport and Kiel classifications.

One-hundred and ninety-four adult patients with histologically proven stage III and IV non-Hodgkin's lymphomas, treated with CVP (cyclophosphamide, vincristine and prednisone) alternated with ABP (adriamycin, bleomycin and prednisone), were analyzed to test the validity of the clinicoprognostic correlation offered by the working formulation in comparison with the Rappaport and Kiel classifications. Actuarial overall survival at 5 yr showed a significant difference among the three prognostic subgroups of the working formulation (low grade, 53.3%; intermediate grade, 47.5%; high grade, 27.7%). Overall survival of favorable subgroups of the Rappaport and Kiel classifications was superior to that of unfavorable prognostic groups. The percentage of systemic symptoms and bulky disease increased in patients with low-grade compared to those with intermediate-grade and intermediate-to-high-grade malignancy. The achievement of complete remission was not related to any of the prognostic groups of the Working Formulation, and no difference could be detected within the various prognostic groups of the Rappaport and Kiel classifications. Within the diffuse histiocytic lymphomas of the Rappaport classification, two groups with a different prognostic outcome were evidenced by the working formulation (G, with an overall survival of 50%, and H, with an overall survival of 26.7% at 5 yr) and by the Kiel classification. The possibility of reporting results in the three different groups of the working formulation instead of two can be considered a step forward. Within the diffuse histiocytic histology, the working formulation allows separation, as does the Kiel classification, into two main different prognostic subgroups.

Adolescent↗
PubMed1983

Non-Hodgkin's lymphomas of Waldeyer's ring.

From 1970 to 1980, 171 consecutive cases with non-Hodgkin's lymphomas (NHL) of Waldeyer's ring were admitted to this Institute. The cases were reviewed to evaluate whether involvement of Waldeyer's ring might represent a distinct clinicopathologic entity. Adequate pathologic staging was performed in 86% of cases. All slides were reviewed, and the histologic diagnosis given according to the Rappaport classification, the Kiel classification, and the recent Working Formulation of NHL for Clinical Usage. Waldeyer's ring alone was involved in 12.3% of the cases at presentation; regional nodes were positive in one-third (35.7%), and distant involvement was detected in half of the patients (52%). The tonsils represented the most frequent site of involvement by NHL within Waldeyer's ring. Treatments employed were heterogeneous, but most of the patients with stage I-II received radiotherapy alone. The present series shows that the association of involvement of Waldeyer's ring and the stomach by NHL occurs in less than 10% of the cases. Treatment results and patterns of recurrence fail to differentiate NHL involving Waldeyer's ring from those of other sites. Prognosis remains related to the classical variables and is independent of the site of onset.

Humans↗
PubMedDate not supplied

Serum levels of interleukin-2 in cancer patients: preliminary considerations.

In order to investigate the production of interleukin-2 (IL-2) in human neoplasms, we determined IL-2 and soluble IL-2 receptors (sIL-2R) in serum from 18 patients with lymphoma and 28 patients with solid tumors, with (15 cases) or without (13 cases) metastases. As controls, 58 healthy subjects were evaluated. Low levels of IL-2 were not observed in patients with lymphoma or limited solid tumor but abnormally low concentrations of IL-2 were seen in 4/15 metastatic solid tumors, associated with abnormally high values of sIL-2R. This preliminary study confirms in vivo the reduced IL-2 production in metastatic solid neoplasms, previously documented in vitro.

Adult↗
PubMedDate not supplied

Chronic effects of subcutaneous interleukin-2 therapy on soluble interleukin-2 receptors in advanced small cell lung cancer.

The increase in IL-2 receptor serum levels is one of the most typical changes in immune parameters during IL-2 cancer immunotherapy. To better define the effects of prolonged IL-2 injection on SIL-2R levels, we evaluated 7 advanced small cell lung cancer patients who received IL-2 subcutaneously at a daily dose of 9 x 10(6) IU/m2/12h for two days followed by 3 x 10(6) IU/m2/12h for 18 days (5 days/week for 4 weeks). Moreover, four patients were also evaluated during the second IL-2 cycle. Venous blood samples were drawn before and at weekly intervals during IL-2 therapy. Mean SIL-2R serum levels rapidly increased with the start of IL-2 injection, and they were significantly higher than the baseline levels throughout the immunotherapy cycle. The increase in mean SIL-2R levels was higher in patients with progressive disease than in those with response or stable disease, but the difference was not significant. Finally, the increase in mean SIL-2R concentrations during the second IL-2 cycle was not significantly different from that seen during the first one. The present study confirms that IL-2 administration determines an evident increase in SIL-2R levels; moreover, it would demonstrate that re-exposure to IL-2 after a rest period does not induce a more pronounced SIL-2R release.

Biomarkers, Tumor↗
PubMedDate not supplied

Anaplastic lymphoma kinase (ALK) is not expressed in Hodgkin's disease: results with ALK-11 antibody in 327 untreated patients.

The t(2;5)(p23;q35) or other rare chromosomal abnormalities involving 2p23 upregulate the ALK gene, which is not expressed in normal lymphocytes. Thus, detection of ALK protein is presumptive evidence of these 2p23 abnormalities. The t(2;5) and ALK immunoreactivity are common in anaplastic large cell lymphoma of T/null-cell lineage. However, a small subset of cases of Hodgkin's disease (HD) have been reported to either carry the t(2;5) or express ALK. In this study, we have immunohistochemically evaluated 327 cases of HD with the ALK-11 antibody. ALK-11 is a well characterized polyclonal antibody raised against an intracellular portion of the ALK protein. We detected ALK-11 immunoreactivity in 8 (2.4%) cases of HD. We further studied these positive cases with ALK-1 monoclonal antibody, which reacts with an intracellular portion of ALK, similar to ALK-11. All 8 ALK-11 positive cases were negative for ALK-1. These results indicate that rare cases of HD may react with ALK-11 antibody, similar to previous reports by others using different polyclonal anti-ALK antibodies. However, the absence of ALK-1 expression in these HD cases suggests that ALK protein is not truly present and that polyclonal anti-ALK antibodies may rarely yield non-specific cross reactivity. These results further support the use of anti-ALK antibodies in the differential diagnosis of HD from ALCL.

Adolescent↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease.

PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

Adolescent↗
PubMedDate not supplied

Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2.

Tumor necrosis factor-alpha (TNF-alpha), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-alpha secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-alpha secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-alpha serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-alpha levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-alpha concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-alpha levels in seven evaluable lymphoma patients (NHL: 6; HD: 1)--who did not respond to conventional therapies--during subcutaneous low-dose IL-2 (3 MIU/day, 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-alpha concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-alpha secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-alpha levels in malignant lymphomas.

Adolescent↗