Search PubMed⌕ Search

Biomedical subjects

S Monfardini

Publications and source records attributed to S Monfardini.

At least 73 records · Page 4Linked to original sources
PubMed1996

Vinorelbine treatment of advanced non-small cell lung cancer with special emphasis on elderly patients.

The aim of this study was to investigate the activity and the toxicity of vinorelbine (VNB) in a population of patients with locally advanced inoperable or metastatic non-small cell lung cancer (NSCLC) including elderly patients unfit for cisplatin-based chemotherapy. VNB was administered at a dose of 25-30 mg/m2, intravenously, weekly until progression. Of the 83 patients who entered the study (median age 63 years, number of patients aged > or = 70 years = 23, median performance status = 80, stage IV in 58 patients, previous chemotherapy in 15 patients), 76 were evaluable. One complete remission and 22 partial remissions were noted (30.2% response rate). Toxicity was mild. Median survival was 9 months. No effect of age upon outcome was detected. Thus, single agent VNB is a reasonable option for advanced NSCLC, particularly in elderly patients.

Adult↗
PubMed1996

Pharmacokinetics of vinorelbine in patients with liver metastases.

BACKGROUND: The main elimination pathway of vinorelbine is hepatic metabolism, and the clearance of vinorelbine could be reduced in patients with liver metastases. OBJECTIVES: To study the pharmacokinetics of vinorelbine in patients who have advanced breast cancer with or without liver metastases and to study the relationship between hepatic function and vinorelbine clearance. PATIENTS AND METHODS: We studied 29 patients with advanced breast cancer: 19 with liver metastases and 10 control patients with extrahepatic metastases (mean age, 61 years; age range, 38 to 81 years). The vinorelbine dose was 30 mg/m2 as a short intravenous infusion; the dose was reduced by 50% in patients with bilirubin > 2 mg/dl. Patients were classified by ultrasonographic estimation of the liver volume replaced by tumor (%LVRT). Standard liver function tests and a monoethylglycinexylidide test (a quantitative liver function test based on lidocaine metabolite formation) were performed. Vinorelbine was assayed in plasma by HPLC with fluorescence detection. Vinorelbine determination was impossible in two patients with more than 75% LVRT because of interferences. Pharmacokinetic parameters were calculated with a noncompartimental method and compared by means of the Kruskal-Wallis test. RESULTS: A lower vinorelbine clearance rate was observed in the five patients with more than 75% LVRT (22.9 L/hr/m2) compared with the 10 patients with no liver metastases (48.0 L/hr/m2) and the 12 patients with 25% to 75% LVRT (45.3 L/hr/m2). Terminal elimination half-life and apparent volume of distribution were not significantly different among groups. The monoethylglycinexylidide test had a significant correlation with vinorelbine clearance. (r2 = 0.70; p = 10(-4). CONCLUSIONS: These results support vinorelbine dose reduction in patients with severe liver failure but not in patients with moderate secondary liver involvement. The monoethylglycinexylidide test may prove to be useful for vinorelbine dose individualization.

Adult↗
PubMed1996

Hepatitis C virus and non-Hodgkin's lymphomas.

Hepatitis C virus (HCV) seems to be the aetiologic agent of mixed cryoglobulinaemia, and as this 'benign' lymphoproliferative disorder can frequently develop into more aggressive haematological disorders, this study was undertaken to determine the prevalence of HCV infection in non-Hodgkin's lymphomas. 199 unselected subjects treated by three haematological centres in Northeast Italy were investigated for the presence of HCV infection. As controls, the prevalence of HCV infection was determined in a group of patients affected by other haematological malignancies (153 subjects) and in the general population of the same geographical area in the cohort study called the Dyonisos project (6917 subjects). The presence of anti-HCV antibodies was determined by a commercial kit and, in positive cases, by PCR amplification of the 5' untranslated region of the virus. The HCV genotype was also obtained by PCR amplification of the Core region with type-specific primers. The presence of serum cryoglobulins was determined in each case of NHL. HCV infection was significantly (P < 0.00000001) higher in patients with non-Hodgkin's lymphomas (28.0%) when compared with that of the general population (2.9%), and with the group of patients affected by other malignancies (3.1%). The prevalence is particularly high in low-grade (38.4%), as compared with intermediate (11.4%), or high-grade (15.2%) lymphomas. The presence of the virus is significantly (P < 0.000001) associated with the presence of detectable levels of cryoglobulins. On the basis of these findings. HCV seems to play an important role in the development of low-grade non-Hodgkin's lymphomas.

Adult↗
PubMed1996

Multidrug chemotherapy in the treatment of non-elderly patients with hormone-refractory prostatic carcinoma. A phase II study. North-Eastern Italian Oncology Group (GOCCNE).

OBJECTIVE: The effectiveness of a chemotherapy regimen including cisplatin, epirubicin, and estramustine phosphate was evaluated in a series of young patients with prostate cancer. METHODS: 28 patients with a histological diagnosis of prostatic carcinoma, age < 70 years, performance status (PS) < 2, hormone-refractory status, life expectancy > 3 months, were treated with cisplatin 60 mg/m2 i.v. and epirubicin 60 mg/m2 i.v. every 3 weeks for six cycles. Estramustine phosphate was administered at a dosage of 10 mg/kg p.o. in two divided daily doses during intravenous chemotherapy and until progression thereafter. The response was assessed after three cycles of chemotherapy, evaluating again the disease parameters. In case of partial remission or stable disease, treatment was continued for three additional cycles. The median age was 61.5 years, the median PS was 70. RESULTS: 11 partial remissions, 13 patients with stable disease, and 4 progressions were noted. The response rate (only partial remissions) was 39% (95% confidence limits 21-57%). The median duration of the partial remissions) was 11 (range 6-25) months. A subjective improvement of symptoms was observed in 17 of 19 patients. Toxicity was acceptable with no deaths. The median overall survival was 15 months. CONCLUSIONS: The combination studied had activity in young prostate cancer patients, and our results suggest that this subset of patients needs specifically devised chemotherapy regimens.

Antibiotics, Antineoplastic↗
PubMed1995

The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non-Hodgkin's lymphomas/leukemias.

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

Adolescent↗
PubMed1995

Entry and evaluation of elderly patients in European Organization for Research and Treatment of Cancer (EORTC) new-drug-development studies.

BACKGROUND: This study aimed to determine the extent to which elderly patients (> or = 65 years) currently are being entered in Phase II single-agent studies, and if advanced age is associated with increased toxicity. METHODS: This analysis was based on the age distribution of 2344 patients with various solid tumors entering 16 Phase II EORTC single-agent trials from January 1983 to February 1992. RESULTS: Of the study group, 22% were 65 years or older and 8% were 70 years or older. Delay in dose administration and dose reduction were significantly higher for elderly patients compared with younger patients (P < 0.05). When adjusting for previous chemotherapy pretreatment, no difference between elderly and nonelderly patients was noted in the frequency of grade 3 and 4 hematological toxicity, nausea, vomiting, and diarrhea. A significant higher frequency of episodes of severe oral toxicity (P < 0.05) and alopecia were observed for elderly patients, but a higher proportion (P < 0.05) of elderly patients received drugs for which stomatitis was an established side effect. No significant difference in the frequency of complete plus partial responses was observed between older and younger patients (9% versus 7%). Treatment discontinuation significantly increased with age, ranging from 24% for those younger than 50 years to 33% among elderly patients (x for trend = 12.83, P < 0.001). There was not evidence that excess toxicity was an obstacle to treatment continuation for elderly patients, whereas treatment discontinuation did occur for the older age group more frequently because of loss to follow-up and treatment refusal. CONCLUSION: Selected elderly patients can and should enter new-drug-development protocols without an increased risk of more severe or frequent side effects. A priori exclusion based on an arbitrary chronologic age limit no longer should occur.

Age Factors↗
PubMed1995

Head and neck lymphomas associated with human immunodeficiency virus infection.

OBJECTIVE: To focus on clinicopathologic data of non-Hodgkin's lymphomas (NHLs) of the head and neck area (with lymph nodal or extranodal localization) arising in patients with immunodeficiency virus (HIV) infection. PATIENTS: Among 73 evaluable patients for presenting symptoms, of a total of 82 with HIV-related NHLs whose conditions were diagnosed at the Centro di Riferimento Oncologico, Aviano (Italy), between September 1984 and May 1992, 15 (21%) had primary, solitary head and neck (P-HN) lymphoma and 13 (18%) had systemic head and neck (S-HN) lymphoma arising from this region. RESULTS: Ten (67%) of 15 patients with P-HN NHL had stages I and II, whereas all patients with S-HN NHL had stages III and IV. Twenty-seven of 28 patients had extranodal disease at presentation, the principal sites being Waldeyer's ring and soft tissues. There were only high-grade (14 cases) or intermediate-grade (three cases) NHLs, the most frequent histotypes being small noncleaved cell, Burkitt's type, and large-cell immunoblastic. Seven of 11 cases in the miscellaneous group of the working formulation were classified as Ki-1+ anaplastic large-cell lymphoma. By immunophenotypic and genotypic characterization, a B-cell derivation was suggested for 21 of 28 NHLs. After combination chemotherapy with or without radiotherapy, a complete remission was observed in seven (58%) of 12 patients with P-HN lymphoma and in only two patients with S-HN lymphoma. Median survival was 9.8 months for the patients with P-HN lymphoma and 8.3 months for the other patients. Thirteen patients died, the most common causes of death being opportunistic infections (five cases) and progression of lymphoma (four cases). CONCLUSIONS: Most HIV-infected patients with head and neck NHL had severe immunodeficiency, extranodal disease, aggressive histologic findings, and a poor treatment response.

Adult↗
PubMed1995

CD30 (Ki-1)-positive anaplastic large-cell lymphomas in 13 patients with and 27 patients without human immunodeficiency virus infection: the first comparative clinicopathologic study from a single institution that also includes 80 patients with other human immunodeficiency virus-related systemic lymphomas.

PURPOSE: CD30 (Ki-1)-positive anaplastic large-cell lymphoma (Ki-1 ALCL) rarely has been described in patients with human immunodeficiency virus (HIV) infection. The purpose of this study was to characterize further the clinicopathologic features of Ki-1 ALCL in patients with HIV infection and, for the first time, to make a comparison with Ki-1 ALCL in patients without HIV infection. PATIENTS AND METHODS: From September 1987 to April 1993, 93 patients with HIV infection and systemic non-Hodgkin's lymphoma (NHL) were treated at the Cancer Center of Aviano, Italy; in 13 (14%), the diagnosis was of Ki-1 ALCL subtype. This group of patients was compared with the remaining 80 patients who had other HIV-related NHL and with another group of 27 patients with Ki-1 ALCL who were without a diagnosis of HIV infection. RESULTS: There was no case of a T-cell phenotype in the 13 HIV-positive Ki-1 ALCL patients, whereas there was such a phenotype in six of 27 (22%) HIV-negative Ki-1 ALCL patients. In regard to the general characteristics of the two groups with Ki-1 ALCL, more patients with stage IV, two or more extranodal sites at presentation, treatment-related leukopenia, and opportunistic infections as the cause of death were observed in the HIV-positive Ki-1 ALCL group. When these variables were compared with those of the other HIV-related NHL group, such differences were not present. CONCLUSION: Ki-1 ALCL is not a rare clinicopathologic entity among NHL in patients with HIV infection. The differences observed within the two Ki-1 ALCL groups of patients may be because of factors related to the HIV infection alone.

Adult↗
PubMed1995

Clinical Trials in Older Patients With Intermediate and High-Grade Lymphomas.

The number of studies concerning non-Hodgkin's lymphoma (NHL) in elderly patients has increased in the last few years. However, the effectiveness of treatments specifically devised for elderly patients with aggressive lymphoma must be determined despite a trend towards reduction of treatment-related death. Direct comparison of trial results is difficult since different age limits were set for the inclusion of patients on study, but we can confirm that the complete response rate decreases with increasing age. Comparison of results even among trials conducted on patients of the same age remains difficult due to the lack of homogeneity in prognostic factors related to the NHL as well as to associated comorbidity, mental status, physical activity and family and social status.

Journal Article↗
PubMed1994

Combined antineoplastic and antiretroviral therapy for patients with Hodgkin's disease and human immunodeficiency virus infection. A prospective study of 17 patients. The Italian Cooperative Group on AIDS and Tumors (GICAT).

BACKGROUND: The optimal therapeutic approach for patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection is unknown. In an attempt to improve the results obtained with standard chemotherapy and to decrease the occurrence of opportunistic infections (OI) during chemotherapy and follow-up observed in a previous experience, the authors designed a prospective combined antineoplastic and antiretroviral approach. METHODS: Between March 1989 and March 1992, 17 consecutive previously untreated patients (median age, 30 years) with HD and HIV infection were enrolled. They had Stage III and IV or Stage I and II disease with adverse prognostic factors. The median CD4+ cell count was 184/microliters. Patients were stratified in two groups and treated accordingly. Group A was made up of patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than 3 and without OI. These patients received epirubicin 70 mg/m2 intravenously on day 1, bleomycin 10 mg/m2 IV on day 1, and vinblastine 6 mg/m2 IV on day 1 (regimen EBV). Group B was made up of patients with PS of 3 or greater or previous OI who had received a 50% reduced dose of epirubicin and vinblastine and a full dose of bleomycin. Courses were repeated every 21 days for six cycles. Zidovudine was given at the dose of 500 mg/day from the beginning of chemotherapy in Group B and after the third cycle in Group A. RESULTS: Overall, 14 of 17 (82%) patients had an objective response and 9 of 17 (53%) achieved a complete remission (CR) of disease for a median duration of 20 months. Toxicity was moderate with Grade 3-4 leukopenia in eight patients and Grade 3 thrombocytopenia in one patient. Thirteen of 17 patients received zidovudine as planned with a median duration of 9 months. Only one patient had OI during or after chemotherapy (median follow-up, 11 months). No worsening of HIV markers during the combined therapy was seen, with the median CD4+ cell count before and after therapy being 184/microliters and 203/microliters, respectively. The median survival time was 11 months, with an actuarial survival rate of 48% at 36 months. The median survival time for the nine patients with CR has not been reached at the time of this analysis. CONCLUSIONS: These results revealed the feasibility and the activity of the combination of EBV regimen and zidovudine. Objective response rate seems similar to those previously observed in patients receiving standard chemotherapy, but only one patient had OI, and this compares favorably with the 16 OI observed in 28 patients treated with standard chemotherapy (6% versus 57%) in the authors' previous experience. Thus, it seems that the addition of antiretroviral therapy to the EBV regimen decreased the occurrence of OI during chemotherapy or follow-up.

Adult↗
PubMed1994

Multimodal treatment of locally advanced transitional cell bladder carcinoma in elderly patients.

22 patients with locally advanced (T3-T4, M0) transitional cell bladder carcinoma, age greater than 70 years, with medical contraindication or refusal of radical cystectomy, were treated following an ample transurethral resection (TUR), with three chemotherapy cycles. Each cycle consisted of 5-fluorouracil 500 mg/m2 intravenously (i.v.) on days 1 and 8, epirubicin 60 mg/m2 i.v. on day 1 and cisplatin 50 mg/m2 i.v. on day 1. Cycles were repeated every 3 weeks. Subsequently, patients were submitted to a repeat TUR on the area of the initial neoplasm. At computed tomography (CT) scan evaluation, response rate to chemotherapy was 54.5%, with two complete responses. No residual disease (R0) at postchemotherapy TUR was encountered in 8 cases (36%), and microscopic disease (R1) in 4 cases (18%). Median duration of complete responses (R0) was 13.5 months (range 7-57+). Radiation therapy was carried out in 12/14 patients with residual disease at repeat TUR. Overall median duration of response was 10.2 months, while overall actuarial median survival was 11.6 months. Four-year survival was 29%. The approach described was feasible. The chemotherapy regimen employed was not as active as current regimens used in younger patients. The search for more active regimens which are tolerable by the elderly is important.

Aged↗
PubMed1994

Cost-benefit of granulocyte colony-stimulating factor administration in older patients with non-Hodgkin's lymphoma treated with combination chemotherapy.

BACKGROUND: Older patients with non-Hodgkin's lymphoma (NHL) display a poorer response to chemotherapy and a significantly higher treatment-associated toxicity than do younger individuals. We investigated the potential clinical benefits and the cost-effectiveness of accelerated granulocyte recovery induced by recombinant granulocyte colony-stimulating factor (G-CSF) in patients with aggressive NHLs, aged 60-70 years, during treatment with a second-generation combination chemotherapy. PATIENTS AND METHODS: 12 consecutive patients (median age 66 years) treated with six to eight courses of CHVmP/VB plus subcutaneous G-CSF (5 micrograms/kg/day) were compared with 11 consecutive subjects (median age 65 years) who received the same chemotherapy regimen without growth factor support. The two groups of patients were fully comparable as to the clinicopathologic features. A comparative analysis of treatment costs (including hospitalization, antimicrobial prophylaxis and therapy, supportive and diagnostic procedures, and G-CSF) was also performed. RESULTS: Both the overall response rate and the percentage of complete remissions were comparable in the two treatment groups. In the control group, 32.5% of chemotherapy courses were delayed, as opposed to 19% in the G-CSF group (p = 0.05). The mean duration of delay for patients receiving or not receiving G-CSF was 10.1 and 25.9 days, respectively (p = 0.02). Grade 3 and 4 granulocytopenia complicated 27.7% of chemotherapy courses in control patients and only 4.8% in subjects receiving G-CSF (p < 0.001). Similarly, severe infections and mucositis were significantly higher in patients receiving chemotherapy alone (15.6% and 3.6%, respectively) compared to the G-CSF group (4.8%, p = 0.01; p = 0.04, respectively). A mean of 1.1 days/course of hospitalization was required in the control group, as opposed to 0.2 days/course in patients receiving G-CSF (p = 0.05). Although overall treatment costs were higher in the control group, single cost of the recombinant growth factor exceeded by far all the other expenses in the G-CSF group, reaching a statistical relevance (p = 0.01). CONCLUSIONS: The inclusion of prophylactic G-CSF in the treatment plan for aggressive NHL in older patients appears safe and cost-effective in view of the peculiar clinical features of aged subjects and the possibility of delivering effective doses of antineoplastic drugs on an outpatient setting.

Age Factors↗
PubMed1994

Hodgkin's disease in patients with HIV infection and in the general population: comparison of clinicopathological features and survival.

BACKGROUND: Hodgkin's disease (HD) has been described in patients with HIV infection in association with unfavourable prognostic factors. Similarly, HD in the older general population has a poorer prognosis than in younger patients. PATIENTS AND METHODS: With the aim of comparing the clinicopathological features and survival of HD in HIV-infected patients and in the general population, we analysed 176 patients with HD from 1986 to 1992. We divided the 84 HIV-negative patients into two groups: group A included patients less than 55 years old, group B patients of 55 years or older. This division was made in order to compare HD in HIV-infected patients with the less favourable group of patients with HD in the general population, i.e., older patients. RESULTS: Patients of the older group and HIV-infected patients had a significantly lower frequency (31% and 21%, respectively) of nodular sclerosis subtype compared to the younger group (85%). Mixed cellularity (MC) is significantly more frequent both in the older group and in HIV-infected patients. Lymphocyte predominance is more frequent (16%) in older patients than in the other two groups. HIV-infected patients are more likely to show advanced stages, B symptoms, and extranodal involvement. Chemotherapy (CT) alone has been the most widely used (83%) treatment in HIV-infected patients, while CT plus radiotherapy (RT) has been mostly employed in the general population. Twelve (14%) HIV-infected patients did not receive any treatment. Complete remission was achieved in 51% of the cases in the HIV-infected patients, and around 90% of the cases in the general population. The estimated 4-year survival rate in the HIV-infected patients is much lower (33%) than in the other two groups (100% in group A, and 88% in group B). CONCLUSION: While MC is the most common histological subtype both in HIV-infected patients and in the older general population, HD in HIV-infected patients has a worse prognosis than in the older general population, not only because of underlying HIV infection, but also because of the more unfavourable clinicopathological features at presentation.

Actuarial Analysis↗