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V Torri

Publications and source records attributed to V Torri.

72 records · Page 4Linked to original sources
PubMed1993

Dose intensity analysis in advanced ovarian cancer patients.

To determine if chemotherapy dose intensity influences treatment outcome in advanced ovarian cancer, all randomised studies of first line chemotherapy, published between 1975 and 1989, were analysed for relationships between planned dose intensity and (a) objective response and (b) median survival. Total dose intensity of each study regimen was calculated and a weighted regression model providing for systemic differences in response or survival among studies was utilised. Hence, treatment arms of different studies were never directly compared. In addition, relative dose intensities of individual drugs within combinations was similarly evaluated. The improvement in objective response rate when adding one unit of total dose intensity ranged between 12% and 16% depending on baseline response rate. The improvement in median survival when adding one unit of total dose intensity ranged between 2 and 4 months. One unit of total dose intensity corresponds to, for example, 20 mg m2 week of cisplatin, or 25 mg m2 week of doxorubicin, or 350 mg m2 week of cyclophosphamide. The analysis of individual drugs suggested that doxorubicin and the platinum compounds were about equally effective, with cyclophosphamide being less effective. The methodological benefits and limitations of the approach used and the implication of the results are discussed.

Antineoplastic Agents↗
PubMed1993

Chronic oral etoposide in small-cell lung cancer: clinical and pharmacokinetic results.

AIMS: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of chronic oral etoposide (E) in patients (pts) with small-cell lung cancer (SCLC) previously untreated with chemotherapy. PATIENTS AND METHODS: Twenty-seven (14 extensive-, 13 limited-stage) pts receiving 100 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of weekly 24-hour drug concentrations. RESULTS: Among 25 evaluable pts, 60% (95% CI: 39%-79%) overall response, 144 and 217 days of median PFS and survival. Dose-limiting non-cumulative neutropenia of high interpatient variability. Linear reduction (30% per week) of absolute neutrophil counts (ANC) up to the 3rd week, recovering the following week. Risk factors for neutropenia (age, PS, serum creatinine and albumin) not identified. High inter-patient variability of 24-hour E plasma levels. A weak correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC, but higher relative decrease of ANC in pts with 24-hour E plasma levels of > 0.32 microgram/ml. CONCLUSIONS: Chronic oral E is effective in SCLC pts previously untreated with chemotherapy. Careful hematological monitoring is essential to avoid severe myelosuppression. The degree of neutropenia might be related to the maintenance of a critical drug concentration level for a critical period of time.

Administration, Oral↗
PubMed1993

Inappropriate Halsted mastectomy and patient volume in Italian hospitals.

To study whether Halsted mastectomy was used only when properly indicated, a prospective survey was undertaken on the process of care of 985 breast cancer patients seen consecutively at 62 general hospitals in Northern and Central Italy. Overall, 79% of Halsted mastectomies were performed inappropriately. The procedure was less likely to be performed on more educated patients and, other factors considered, on those seen at hospitals with larger volume. We conclude that the measurement of utilization of a surgical procedure for which only a few appropriate indications exist may help identify important relationships between hospital characteristics and quality of surgical care.

Adult↗
PubMed1992

Statistical model to determine the relationship of response and survival in patients with advanced ovarian cancer treated with chemotherapy.

BACKGROUND: A statistically appropriate analysis of the association between survival and response measures in patients with ovarian cancer could help to define the role of response rate in planning, monitoring, and interpreting the results of clinical trials. PURPOSE: This study was designed to investigate the relationship between antitumor response determined by clinical or pathological means and survival in patients with advanced ovarian cancer with no previous treatment. We focused on avoiding the limitations of the usual approach of comparing durations of survival for patients responding to therapy with those for nonresponders. METHODS: A new meta-analytic statistical model we developed was used to analyze data from 26 randomized clinical trials published between 1975 and 1989. Our model incorporates intra-study and inter-study sources of variability in the estimates of response and survival. The study also addresses the methodological problems of evaluating response as a surrogate end point and the relevance of this association to clinical decision making and the design of clinical trials. RESULTS: For 13 studies in which response was pathologically assessed, an improvement in surgically documented complete response rate was associated with an increase in median survival. A similar but apparently smaller effect was found for the association between objective clinical response and median survival in the 25 studies reporting these data. CONCLUSIONS: These results suggest that therapeutic measures must produce large improvements in clinical response rates to achieve meaningful effects on median survival. Improvement in surgically documented complete response rate appears to be more strongly associated with increased median survival and, hence, might be used for interim monitoring in clinical trials, but the role of second-look procedures in clinical management is controversial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

The role of attitudes, beliefs, and personal characteristics of Italian physicians in the surgical treatment of early breast cancer.

The influence of Italian physicians' attitudes, beliefs, and personal characteristics on medical decision making is examined in the case of surgical treatment of early breast cancer. Responses to a mail survey of 657 physicians from different specialties were analyzed comparing doctors recommending a radical procedure (9%) to those preferring a conservative procedure for younger patients only (25%), and those considering conservative surgery the treatment of choice regardless of patients' age (66%). The findings suggest that the likelihood of physicians' preferring a conservative procedure is influenced by their specialty and the extent to which they feel that a patient should have a role in the treatment decision more than by differences in the beliefs of treatment outcomes. Only preferences of the small group indicating radical surgery as the sole admissible treatment can be accounted for by ignorance or distrust of results of recent trials. These findings suggest that other than scientific factors guide many doctors in their decision making; they may help to explain why the diffusion of research results into clinical practice is often disappointingly slow.

Adult↗
PubMed1990

Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

Age Factors↗
PubMed1990

The impact of cancer treatment guidelines on actual practice in Italian general hospitals: the case of ovarian cancer.

Over the past ten years the Italian National Research Council (C.N.R.) has carried out an educational program based on the preparation and dissemination of guidelines to facilitate delivery in community hospitals of the most up-to-date care to patients with ovarian cancer. In 1988 an assessment was begun to determine (a) whether the guidelines reached the target physician population; (b) whether they were accepted by those they reached, and (c) whether treatment patterns thereafter conformed to the guidelines. Overall results of this evaluation provide no evidence of clinically relevant effects of the program. The guidelines were not widely disseminated: only 44% of responders were aware of them. Moreover, analysis of practice patterns showed serious deficiencies in diagnostic procedure and surgical staging (information on grading and residual tumour was available only in 30% and 45% of cases, respectively, and only 10% of the patients had random biopsies as part of their surgical staging). The only observation supporting some effect of this educational intervention in terms of knowledge modification was of certain therapeutic preferences among those aware of the guidelines. This finding, however, is highly susceptible to confounding by other factors (e.g. physicians' greater expertise, spillover effect of the program) not entirely avoidable in an observational study. We conclude that any assessment of procedures based on dissemination of information must include a careful analysis of the method of dissemination. The availability of clinically applicable information must also be realistically appraised before the guidelines approach can be accepted as the most effective.

Adult↗
PubMed1989

Quality, evolution, and clinical implications of randomized, controlled trials on the treatment of lung cancer. A lost opportunity for meta-analysis.

A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients' characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non-small-cell lung cancer-despite the persistent lack of proof of efficacy of any active treatment-an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable-though limited-progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.

Combined Modality Therapy↗
PubMedDate not supplied

The multi-centre assessment of quality of life: the Interdisciplinary Group for Cancer Care Evaluation (GIVIO) experience in Italy.

One of the main issues to be considered in conducting clinical trials concerns the presence of missing data. This aspect is particularly relevant in oncology longitudinal studies, characterized by a long follow-up, and especially in quality of life studies where there is still little knowledge about patients' characteristics that predict loss of data. Since the middle of the 1980s the GIVIO (Interdisciplinary Group for Cancer Care Evaluation) co-operative group has been involved in conducting quality of life assessment studies, also focusing on the development of some strategies aimed at the minimization of missing data. In this paper we report on the results of two trials, which are now completed, concerning the quality of life assessment in a sample of breast and colon cancer patients. In order to cope with the problem of missing data, in both the trials the strategy of follow-up mailing was adopted, which proved to be an effective way to increase the response rate by nearly 50 per cent at each time point.

Adenocarcinoma↗
PubMedDate not supplied

How tumor markers are used in the routine follow-up of breast and colorectal cancer. A survey of 29 Italian hospitals.

The impact of tumor markers on the outcome of several malignancies is still under debate. This relative uncertainty leads to a subjective approach to their use. Monitoring the use of tumor markers is a valuable tool to identify the need for educational policies. We conducted a survey to evaluate how tumor markers are routinely used in the follow-up of patients with breast, colorectal and ovarian carcinoma. The former two malignancies are considered in the present paper. We surveyed 35 Italian hospitals; 29 (83%, accounting for 26,622 hospital beds) filled in and returned the questionnaire. Overall, 467,361 tumor marker requests were scrutinized by the surveyed hospitals. We found a wide variability in the type and number of routinely used markers, the cutoff points chosen, and the clinical decisions taken on the basis of marker results. In addition, we observed a relative lack of communication between clinicians and clinical pathologists in around 50% of the surveyed hospitals. In these cases clinical information was not provided to the laboratory and methodological aspects were not communicated to clinicians. From the findings of the present study we conclude that the cooperation between clinicians and clinical pathologists must improve before guidelines for the use of tumor marker assays can be framed and the compliance with these guidelines can be checked. Request forms for tumor marker assays should therefore be designed to contain clinical information and the quality of filling in request forms with clinical data should be carefully monitored.

Biomarkers, Tumor↗
PubMedDate not supplied

Cell cycle-related phosphatases CDC25A and B expression correlates with survival in ovarian cancer patients.

Alterations in cell cycle regulating proteins are common in many cancer types. Recent data suggest a possible link between CDC25 phosphatases overexpression and malignancy. Our objective was to evaluate the expression of the three cell cycle-related phosphatases CDC25A, CDC25B and CDC25C in patients with ovarian cancer. All the patients had a minimal follow up of three years. CDC25A, CDC25B and CDC25C expression were investigated by immunohistochemistry in 106 patients with ovarian cancer. CDC25A and CDC25B were found expressed in almost all the samples analyzed, while CDC25C was undetectable in more than 80% of the patients. The low evaluable data on CDC25C expression, did not allow any association between the expression of this phosphatase and prognosis. The expression of CDC25A and CDC25B showed some evidences of association with a poor prognosis (p = 0.034 and p = 0.058 respectively). This relationship was independent of other factors such as tumor grade, histotype, stage and residual tumor after surgery. In the same patients the examined parameters (residual tumor, grade, stage and histotype) did show the expected relation with survival. The results indicate that high CDC25A and CDC25B expression is related to a worse prognosis in ovarian cancer patients. CDC25 phosphatases expression can be regarded as a possible prognostic factor for ovarian cancer and these proteins should be evaluated as potential molecular targets of novel drugs against this human neoplasm.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Therapeutic impact of adult-type acute lymphoblastic leukemia regimens in B-cell/L3 acute leukemia and advanced-stage Burkitt's lymphoma.

BACKGROUND: Adult B/L3-ALL is a rare disease subset characterized by an aggressive clinical course and a poor response to conventional adult ALL-type chemotherapy. Recent data from the GMALL Group showed that prognosis can be improved with an innovative treatment regimen. In the current retrospective survey we focus on therapeutic results obtained at our Institutions during a 15-year period with ALL-type regimens in 34 adults with either B/L3-ALL or advanced-stage Burkitt's lymphoma. METHODS: Five successive ALL treatment programs were developed. They included a homogeneous induction phase with early intrathecal chemoprophylaxis, multidrug postremission consolidation followed by cranial irradiation (4 trials), high-dose chemotherapy plus autografting (2 trials), late consolidation (2 trials), and variable-length maintenance (4 trials). Early response and prolonged disease-free survival rates were analyzed according to selected clinical and therapeutic variables. RESULTS: Overall, a complete remission was achieved in 62%, with a median duration of 1.6 years and a 10-year remission rate of 49%. A diagnosis of B/L3-ALL (p = 0.007), the use of idarubicin instead of adriamycin during induction (p = 0.018), a serum creatinine < 1.6 mg/dL, and an uninvolved central nervous system were associated with higher response rates. As regards long-term disease-free survival, results were significantly better in patients with < 1 x 10(9)/L L3/blast cells in the peripheral blood (p = 0.0029) and/or aged < 50 years (p = 0.04), and in those consolidated with the most recent rotational high-dose plus peripheral blood stem cell autotransplant regimen. CONCLUSIONS: According to the results presented, ALL-like regimens may still represent a worthwhile therapeutic choice. The use of idarubicin during induction, the prognostic subclassification of patients, a careful control of dysmetabolic complications, the selection of the proper chemo-radioprevention for meningeal disease and perhaps the introduction of high-dose chemotherapy supported by autologous stem cell rescue appear to be the mainstay of further improvements.

Adolescent↗