Malignant pleural mesothelioma.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
B Castagneto
Publications and source records attributed to B Castagneto.
HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients.
No data are available on the role of HER2 overexpression in predicting the efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. We retrospectively evaluated this role in patients enrolled in a phase III study comparing standard FEC21 (5-fluorouracil, epirubicin, and cyclophosphamide, administered every 3 weeks) vs dose-dense FEC14 (the same regimen repeated every 2 weeks). HER2 status was determined for 731 of 1214 patients. Statistical analyses were performed to test for interaction between treatment and HER2 status with respect to event-free survival (EFS) and overall survival (OS); EFS and OS were compared within each HER2 subgroup and within each treatment arm. Median follow-up was 6.7 years. Among FEC21-treated patients, both EFS (HR=2.07; 95% CI 1.27-3.38) and OS (HR=2.47; 95% CI 1.34-4.57) were significantly worse in HER2 + patients than in HER2 - patients. Among FEC14-treated patients, differences in either EFS (HR=1.21; 95% CI 0.65-2.24) or OS (HR=1.85; 95% CI 0.88-3.89) between HER2 + and HER2 - patients were not statistically significant. Interaction analysis suggested that the use of dose-dense FEC14 might remove the negative prognostic effect of HER2 overexpression on EFS and OS. Our data suggest a potential role of HER-2 overexpression in predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the need to confirm this hypothesis in future prospective studies.
Antibiotics, Antineoplastic↗
Limits of aortic stop flow infusion chemotherapy in the treatment of advanced cancer.
BACKGROUND: Advanced and relapsed tumors remain a challenging disease with a poor and dismal prognosis. Our choice for inoperable tumors consists in a percutaneous treatment strategy involving intra-arterial chemotherapy and hemofiltration, with previous blood stop-flow, which allows high doses of Cisplatin-cisplatinum, cis-diammine-dichloroplatinum (CDDP) and Mitomycin C (MMC) in the tumor-bearing area with minimal systemic toxicity. METHODS: We analyse the morbidity and mortality associated with stop-flow in 20 patients with unresectable and/or metastatic thoraco- abdominal tumors, non responders to prior systemic chemotherapy. RESULTS: In our experience, the rate of major side effects of the procedure was 31% with a mortality of 5%. The side effects were related to the radiological procedure and to the chemotherapic treatment. A 74-year-old patient died for acute kidney toxicity within 15 days after the procedure. The other transient toxicity symptoms recorded were: nausea, vomiting, increasing of creatinine levels, diplopia and appearance of necrotic ulcer associated to chemotherapic drugs. Concerning the complications related to the radiological technique, the main problem was the rupture of the balloon stop-flow catheter in four patients. CONCLUSIONS: Stop-flow is a new procedure that could develop in the future, thanks to the possibility of obtaining a higher dose intensity of chemotherapic drugs in districts or organs affected by advanced tumors, with less systemic side effects. Unfortunately, the uncertain results in terms of increasing survival and the default of effective devices are to be resolved for a wider application of the procedure.
Adult↗
Establishment of four new mesothelioma cell lines: characterization by ultrastructural and immunophenotypic analysis.
The aim of this study was to assess the biological characteristics of four new malignant mesothelioma (MM) cell lines. Since simian virus (SV)40 sequences have been recently detected in MM, SV40 large T antigen (Tag) expression was also analysed. MM cell lines were characterized by morphological, ultrastructural and cytogenetic analysis. Expression of Tag and of relevant MM markers was studied by immunocytochemistry, surface antigens by indirect immunofluorescence and immunomodulating cytokines by enzyme-linked immunosorbent assay (ELISA). The four MM cell lines, established from pleural effusions, showed a slow proliferation rate and pleomorphic changes during culture. Cell lines expressed vimentin, cytokeratins 8 and 18, and the mesothelial antigen recognized by HBME-1 monoclonal antibody, but not carcinoembryonic antigen. Surface human leukocyte antigen (HLA)-class I and intercellular adhesion molecule (ICAM)-1 molecules were present on all the cell lines. While HLA class II and CD86 were constitutively undetectable, HLA-class II was present after interferon (IFN)-gamma stimulation. All cell lines displayed abnormal karyotypes with chromosome 6 abnormalities. Transforming growth factor (TGF)-beta2 and interleukin (IL)-6 were constitutively secreted, while tumour necrosis factor (TNF)-alpha was secreted only in response to lipopolysaccharide. Intranuclear Tag was expressed in two cell lines. The persistence of large T antigen with human leukocyte antigen class I and intercellular adhesion molecule-1 positivity may point to large T antigen as a target for cytotoxic T-lymphocyte-based immunotherapy in some malignant mesothelioma patients.
Antigens, Differentiation, T-Lymphocyte↗
Immunobiology and immune defense mechanisms of mesothelioma cells.
Malignant mesothelioma (MM) is an aggressive tumor whose incidence is expected to rise in future years. Patients with this neoplasm have a poor prognosis. Immunotherapy has been shown to be effective in some neoplasms (e.g. melanoma), significantly improving their prognosis but we do not yet have sufficient data on the capability of MM cells to elicit an immune response. A "three step" event is required to determine an immune response: adhesion, recognition, and costimulation between the antigen presenting cells and the immunoeffector cells. Lack of one of these three steps leads to a defective immune response. The most important mechanism determining the defective immune response to the tumor cells is supposed to be the deficiency of the molecules involved in this "three step event", the release of immuno-depressant factors by the tumor cells and/or the tumor infiltrating cells and the lack of surface immunogen epitopes. Investigations on MM cells are not univocal, suggesting that, at least in some cases, an effective immune response to this neoplasm can occur. Blocking the release of immunodepressant factors by malignant mesothelioma cells and identification of effective, specific immunogen epitopes seem to be the most promising objective to achieve.
Asbestos↗
Recurrent chromosome 6 abnormalities in malignant mesothelioma.
The long latency period between asbestos exposure and the onset of malignant mesothelioma (MM) suggests that a multistep tumorigenesis process occurs whilst the capability of asbestos fibres to interfere directly with chromosomes focuses on the critical role of the chromosomal abnormalities in this neoplasm. The aim of our study was to identify any recurrent chromosomal changes in ten primary MM cell cultures derived from pleural effusions of patients with MM from the same geographic area and environmental and/or occupational exposure to asbestos fibers. Cytogenetic analysis was performed in accordance with International System for Human Cytogenetic Nomenclature. Our results confirmed a great number of cytogenetic abnormalities in MM cells. Recurrent loss of the long arms of chromosome 6 (6q-) was the most frequent abnormality detected (four epithelial and two mixed subtypes) while, on the whole, abnormalities of chromosome 6 were found in nine out of ten cases whereas chromosome 6 was normal only in the case with fibromatous subtype. Monosomy 13 and 17 was found in five cases, monosomy 14 in four cases and 22 in three cases. Since deletion of 6q- was detected even in relatively undisturbed karyotype, we hypothesize a multistep carcinogenic process in which deletion of 6q- is an early event in the development and progression of malignant mesothelioma.
Adult↗
Recombinant interferon alpha-2b in the treatment of diffuse malignant pleural mesothelioma.
Fourteen patients with diffuse malignant pleural mesothelioma (DMPM) were enrolled in a Phase II study to assess activity and toxicity of the systemic administration of recombinant (r)-alpha-interferon (IFN)-2b. The IFN schedule was: 3 x 10(6) IU i.m. days 1-4, 6 x 10(6) IU days 5-8, 10 x 10(6) IU days 9-12; then IFN was administered at 10 x 10(6) IU 3 days/week. If grades II-III toxicity occurred, IFN dose was reduced and drug continued at the previous dose level. All patients were evaluated by CT scan. Only one patient was not evaluable for response and toxicity because of inadequate follow-up. Of 13 evaluable patients, we observed 1 objective response, 6 stable disease, and 6 failures (3 progressive disease and 3 early interruptions due to subjective toxicity). The median time to progression was 19 weeks, and the median overall survival was 62 weeks. Toxicity was mild: of 13 patients evaluable for toxicity we observed fever (9 patients), flu-like syndrome (3 patients), fatigue (4 patients), anorexia (2 patients), myelosuppression (3 patients), and muscle pain (1 patient). The results of this study indicate only marginal activity of r-alpha-IFN in the treatment of DMPM.
Aged↗
Gamma/delta T-lymphocytes in advanced pulmonary asbestosis.
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Asbestosis↗
Mortality from respiratory and digestive cancers among asbestos cement workers in Italy.
A cohort study is presented on the mortality of blue-collar workers in an asbestos-cement production plant that has been operating since 1907. Use of both crocidolite and chrysotile is reported. The cohort includes 2608 men and 759 women who were employed in the plant on Jan. 1, 1950 and those who started to work between 1950 and 1980. Follow-up was terminated on April 15, 1986 with 97.9% traced. Expected deaths were estimated from the age- and sex-specific regional mortality rates for the years 1969 to 1981. The data have been analyzed for the period 1964 to 1986 based on person-years at risk: 43,000 for men and 14,494 for women. A statistically significant increase was found in both sexes for mortality from all causes. From 1964 to 1986, 728 men died from all causes (608 expected), 275 with cancer at any site (158 expected) 110 with lung cancer (41 expected), 28 with pleural tumors (1 expected) and 85 with asbestosis (less than 1 expected). Corresponding figures for women were--all causes: 136 deaths versus 102 expected; all cancers: 79 verses 32 expected; lung cancer: 7 versus 2 expected; pleural tumor: 15 versus 0 expected and asbestosis: 4 versus 0 expected. Deaths from digestive tract cancer were in excess only among women (18 observed versus 10 expected, p less than 0.01). No excess was found for deaths from laryngeal cancer. Standardized mortality rates (SMR) for lung cancer among males showed a clear increase in direct relationship with length of follow-up. SMR according to length of employment were 234 for length 10 to 19 years, 363 for 20 to 29 years, and 256 for 30 years or longer (p less than 0.05 and lower).
Adult↗
Etoposide versus etoposide plus high-dose cisplatin in the management of advanced non-small cell lung cancer. Results of a prospective randomized FONICAP trial. Italian Lung Cancer Task Force.
Two hundred sixteen patients with unresectable non-small cell lung carcinoma were randomly allocated to receive etoposide (120 mg/m2, days 1-3) either alone or in combination with high-dose cisplatin (60 mg/m2, days 1-2). The patients' distribution and characteristics were similar in the two treatment arms. The objective response rate for etoposide was 7% versus 25.8% for etoposide plus cisplatin (P less than 0.005). Median progression-free survival in etoposide arm was 3.5 months versus 5 months in the combination arm (P = 0.43). The median survival time for etoposide was 6 months compared with 8 months for etoposide combined with cisplatin (P = 0.87). Significantly more nausea/vomiting (P less than 0.005), serum creatinine elevation (P less than 0.005), hearing loss and/or tinnitus (P less than 0.005), peripheral neuropathy (P less than 0.005), leukopenia (P less than 0.025), and anemia (P less than 0.005) occurred in the etoposide plus cisplatin arm. No statistically significant difference was recorded between the two arms in terms of performance status changes. In conclusion the addition of high-dose cisplatin to single-agent etoposide significantly increases the chance of obtaining tumor response in advanced non-small cell lung cancer at the cost of an increased toxicity without any significant long-term impact on survival and progression-free survival.
Antineoplastic Combined Chemotherapy Protocols↗
[Cancer of the rectum: analysis of incidence and survival at the Casale Monferato Provincial Hospital].
Between 1978 and 1984, 34 patients carrier of rectal neoplasms, were observed and treated in Divisione di Chirurgia Generale of Casale Monferrato Hospital. Twenty of such patients had been operated with curative procedures and 14 with palliative procedures. At the moment of this investigation 14 patients were still alive. The survival rate at 5 years, referred to '78, '79, '80, '81, respectively was 37.2%. For the last three years, the fifth year delay time shall be waited. The survival rates per year, have been reported her, for the whole period of the investigation. The AA, have evaluated the gross incidence rate for male and female patients (3.1 and 2.1 respectively). Survival and incidence data have been composed to those reported in the literature. Whilst survival rates agree with those from other authors, the incidence rates result considerably lower than those from other West Countries. It could be abscribed to an underestimation of the actual number of rectal neoplasm bearing patients, which could escape the investigation because diagnosticed and treated elsewhere. It should be noted nevertheless that the Casale Hospital supplies a scarcely industrialized urban area, and a wide rural environment, so that resident population might be included within one of the groups partially protected by environmental and alimentary conritions against the disease. In conclusion the AA. consider of a primary importance the development of centres suitable for base medicine aimed at assuring a real and effective prevention activity.
Adenocarcinoma↗
[Occlusive neoplastic pathology of the large intestine (a clinical contribution)].
The Authors report an investigation on 42 patients with large bowel occlusions for neoplastic lesions. Obstruction complications were localized in 69% in sigmoid colon and recto-sigmoid junction. This pathology involved old patients with one or more associated affections. The Authors explain reflections on surgical treatment, on necessity of therapeutic approach in high-risk patients, and of large bowel surgery with oncologic radical treatment.
Adult↗
[Carcinoma of the prostate: statistico-epidemiologic study at Casale Monferrato Hospital (1980-84)].
An investigation on prostatic dancer is reported by AA., along a five years period (80-84) in Casale Monferrato territory (USSL 76, Piedmont) incidence rate (29,8) aid mortality data (27,7) are also reported in comparison to those reported in "Registro Tumori del Piemonte (Turin)", "Registro Tumori Lombardia (Varese)" and ISTAT (national territory). A. marking differencies among reported data, give some explanation about disagreement. AA.'s further assert that the given under-estimation of the incidence rate is due to the different diagnosis in different USSL. The over-estimation of death rate is partially given first by people come back in primitive country of origin, and second by data acquired in original countries, about death.
Aged↗
Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion: Results of a phase II study on 31 consecutive patients.
Malignant pleural mesothelioma is often unresectable at diagnosis, is refractory to cytotoxic agents and is frequently complicated by pleural effusion. The expected survival range for patients with or without involvement of visceral pleura is respectively 1-9 and 9-12 months; mesothelioma-related pleural effusion severely impairs the patients' quality of life and easily relapses after conservative treatments. Intrapleural administration of IL-2 is reported to be effective both in tumor-associated malignant pleurisy and on primary mesothelioma, whereas few data exist about IL-2 systemic administration. In order to assess the palliative and therapeutic activity of IL-2 in unresectable pleural malignant mesothelioma with pleural effusion, we performed a phase II study on 31 consecutive patients (M/F 16/15; median age 61 years, range 40-84; PS ECOG 0 n=7; ECOG 1 n=15; ECOG 2 n=9; stage IA n=13; IB n=9; II n=7; IV=2) who received first-line therapy with intrapleural repeated instillation of 9000000 I.U. IL-2 twice/weekly for 4 weeks, after needle thoracenthesis. In nonprogressing patients, 3000000 I.U. IL-2 were subcutaneously administered thrice weekly for up to 6 months. Toxicity (WHO criteria) with intrapleural IL-2 consisted of grade 3 fever in 6/31 (19%) patients and of cardiac toxicity (failure) grade 3 in one patient (3%); toxicity during subcutaneous treatment was mild to moderate, mainly a flu-like syndrome. In 28/31 (90%) of patients there was no further or minimal (asymptomatic) pleural fluid collection (according to Paladine criteria); pleurisy relapsed only in 1/28 patients after 19 months. Tumor objective response (WHO criteria), evaluated by CT, occurred in seven patients (one CR and six PR; ORR 22%); ten patients achieved SD and 14 patients progressed. Median overall survival was 15 months (range 5-39) in all patients. IL-2 intrapleural administration followed by low-dose IL-2 subcutaneously in pleurisy-complicated malignant mesothelioma is feasible and active both in palliation of pleural effusion and on primary tumor, with manageable toxicity. The overall survival observed in nonprogressing patients warrants further randomized studies with IL-2 aimed to the patient outcome.
Adult↗
Combined epirubicin and interleukin-2 regimen in the treatment of malignant mesothelioma: a multicenter phase II study of the Italian Group on Rare Tumors.
The Italian Group on Rare Tumors undertook a phase II study of a combination of epirubicin and interleukin-2 in 21 chemotherapy-naive patients with malignant mesothelioma. All patients had bidimensionally measurable disease at CT scan. Treatment included Intravenous administration of epirubicin at a dose of 110 mg/m2 i.v. on day 1, and interleukin-2 at a dose of 9 MU subcutaneously from day 8 to day 12 and from day 15 to day 19. Cycles were repeated every three weeks, up to six times in the absence of progressive disease. Treatment response was evaluated after two cycles of therapy. Only one patient achieved a partial response, resulting in an overall response rate of 5% (1/21) with a median progression-free and overall survival of 5 and 10 months, respectively. Toxicity was relevant and caused treatment discontinuation in many patients. These results do not support the use of such a combination in the management of malignant mesothelioma.
Adult↗
[Mortality from tumors and other diseases of the respiratory system in cement-asbestos workers in Casale Monferrato. A historical cohort study].
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Adolescent↗
Expression of intercellular adhesion molecule-1 (ICAM-1) by reactive mesothelial cells in pleural effusions.
Reactive mesothelial cells in serous effusions have been assessed for their capacity to express intercellular adhesion molecule-1 (ICAM-1), when pleural cavities are involved in inflammatory and immune reactions. Cytospin smears prepared from 10 benign and 10 malignant effusion specimens were used in an immunocytochemical procedure. Mesothelial cells were positively immunolabeled by a monoclonal antibody to human ICAM-1, whereas lymphocytes clustered around them reacted positively with a monoclonal antibody to human Lymphocyte Function-associated antigen-1 alpha chain (LFA-1-alpha). The ICAM-1/LFA-1 interaction enables mesothelial cells to regulate leukocyte transmigration to and accumulation in serous cavities and therefore they are actively involved in the development of serous effusions.
Antibodies, Monoclonal↗