Biomedical subjects

Michele De Laurentiis

Publications and source records attributed to Michele De Laurentiis.

8 recordsLinked to original sources

PubMed2005

A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer.

PURPOSE: Experimental data suggest a complex cross-talk between HER-2 and estrogen receptor, and it has been hypothesized that HER-2-positive tumors may be less responsive to certain endocrine treatments. Clinical data, however, have been conflicting. We have conducted a meta-analysis on the interaction between the response to endocrine treatment and the overexpression of HER-2 in metastatic breast cancer. EXPERIMENTAL DESIGN: Studies have been identified by searching the Medline, Embase, and American Society of Clinical Oncology abstract databases. Selection criteria were (a) metastatic breast cancer, (b) endocrine therapy (any line of treatment), and (c) evaluation of HER-2 expression (any method). For each study, the relative risk for treatment failure for HER-2-positive over HER-2-negative patients with 95% confidence interval was calculated as an estimate of the predictive effect of HER-2. Pooled estimates of the relative risk were computed by the Mantel-Haenszel method. RESULTS: Twelve studies (n = 2,379 patients) were included in the meta-analysis. The overall relative risk was 1.42 (95% confidence interval, 1.32-1.52; P < 0.00001; test for heterogeneity = 0.380). For studies involving tamoxifen, the pooled relative risk was 1.33 (95% confidence interval, 1.20-1.48; P < 0.00001; test for heterogeneity = 0.97); for studies involving other hormonal drugs, a pooled relative risk of 1.49 (95% confidence interval, 1.36-1.64; P < 0.00001; test for heterogeneity = 0.08) was estimated. A second meta-analysis limited to tumors that were either estrogen receptor positive, estrogen receptor unknown, or estrogen receptor negative/progesterone receptor positive yielded comparable results. CONCLUSIONS: HER-2-positive metastatic breast cancer is less responsive to any type of endocrine treatment. This effect holds in the subgroup of patients with positive or unknown steroid receptors.

Antineoplastic Agents, Hormonal↗

PubMed2004

Topotecan compared with no therapy after response to surgery and carboplatin/paclitaxel in patients with ovarian cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) randomized study.

PURPOSE: Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. PATIENTS AND METHODS: To investigate whether topotecan (1.5 mg/m(2) on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2) administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. RESULTS: Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P =.83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. CONCLUSION: The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

Adult↗

PubMed2004

Weekly docetaxel and vinorelbine (VIN-DOX) as first line treatment in patients with hormone refractory prostate cancer.

BACKGROUND: The current study investigated the clinical benefit, the impact on biochemical and objective response and tolerability of weekly docetaxel with vinorelbine (VIN-DOX) in symptomatic patients with hormone refractory prostate cancer (HRPC). METHODS: Patients were treated with docetaxel 25 mg/m2 and vinorelbine 20 mg/m2, intravenously for 6 consecutive weeks followed by a 2 week rest repeatedly until disease progression. Clinical benefit evaluations, based on Karnofsky performance status (KPS) and pain measure, were assessed weekly during therapy. A clinical benefit response was defined as a sustained (> or =4 weeks) improvements in one of these parameters. Changes in prostate-specific antigen (PSA) levels, tumoral response and toxicity also were evaluated. RESULTS: 19 men (median age 68 years), were treated. Overall, 42% of patients achieved a KPS significant change and positive pain response; 47% achieved a 50% or greater reduction in PSA. The objective response rate was observed in 2 of 9 patients with measurable disease (22%). The most important toxicity was neutropenia (Grade 3 = 32%). CONCLUSIONS: The combination of weekly VIN-DOX appears to be feasible. VIN-DOX was found to be associated with improvement in clinical benefit response and biochemical response and well tolerated as first line treatment in HRPC.

Adenocarcinoma↗

PubMed2002

Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer.

PURPOSE: The transforming growth factor alpha-epidermal growth factor receptor (EGFR) autocrine pathway has been implicated in prostate cancer cell growth. Amplification and/or overexpression of c-erbB-2, a receptor closely related to the EGFR, has been recently involved in prostate cancer progression. We investigated EGFR and c-erbB-2 expression in primary androgen-dependent and in advanced androgen-independent prostate cancer and their potential role as markers of disease progression. EXPERIMENTAL DESIGN: EGFR and c-erbB-2 expression were evaluated by immunohistochemistry in a consecutive series of 74 prostate cancer patients with the following characteristics: 29 patients (group 1) treated with radical prostatectomy; 29 patients (group 2) treated with luteinizing hormone-releasing hormone analogues and antiandrogen therapy followed by radical prostatectomy; and 16 patients with hormone-refractory metastatic disease. In all patients we evaluated: association between EGFR and/or c-erbB-2 expression and clinicopathological parameters; and disease-free survival according to EGFR and c-erbB-2 expression in univariate analysis (Kaplan-Meier product-limit method) and in multivariate analysis (Cox proportional hazards regression model). RESULTS: EGFR expression was found in 12 of 29 (41.4%) group 1 patients, in 22 of 29 (75.9%) group 2 patients (P < 0.0005), and in 16 of 16 (100%) metastatic patients (P < 0.005), whereas c-erbB-2 expression was found in 11 of 29 (37.9%) group 1, in 10 of 29 (34.5%) group 2 patients, and in 9 of 16 (56.3%) metastatic patients. A significant association was found between EGFR expression and a high Gleason score (P < 0.01) and between EGFR expression and higher serum prostate-specific antigen values (P < 0.02) in all groups of patients. Among the 58 patients treated with radical prostatectomy, 23 of 34 EGFR-positive patients (67.6%) relapsed, whereas only 2 of 24 EGFR-negative patients (8.3%) relapsed (P < 0.00004). c-erbB-2 expression did not significantly correlate with disease relapse (P = 0.07). In a Cox multivariate analysis, the only parameter with an independent prognostic effect on disease-free survival was EGFR expression (relative hazard, 11.23; P = 0.0014). CONCLUSIONS: EGFR expression increases during the natural history of prostate cancer. Correlation with disease progression and hormone-refractory disease suggests that EGFR-targeted drugs could be of therapeutic relevance in prostate cancer.

Androgens↗

PubMedDate not supplied

A novel neural network-based survival analysis model.

A feedforward neural network architecture aimed at survival probability estimation is presented which generalizes the standard, usually linear, models described in literature. The network builds an approximation to the survival probability of a system at a given time, conditional on the system features. The resulting model is described in a hierarchical Bayesian framework. Experiments with synthetic and real world data compare the performance of this model with the commonly used standard ones.

Bayes Theorem↗

PubMedDate not supplied

Is there a standard chemotherapeutic regimen for hormone-refractory prostate cancer? Present and future approaches in the management of the disease.

Prostate cancer that no longer responds to hormonal manipulation can be defined as hormone-refractory prostate cancer. Until recently, there has been no standard chemotherapeutic approach for hormone-refractory prostate cancer. The major benefits of chemotherapy in the treatment of the disease are palliative in nature, in terms of reduction of pain and use of analgesics and improvement of performance status, as followed in the most recent trials. Phase III studies are necessary to better evaluate the efficacy of the different regimens, because several old studies suffer for methodological deficits. There is a promising activity of new drug combinations, such as vinca alkaloids and taxanes. Phase I and II trial are testing combinations of classic chemotherapeutic agents and biologic drugs, and the first results appear interesting. In this article, recent advances in the treatment of hormone-refractory prostate cancer using chemotherapeutic regimens are critically reviewed.

Antibiotics, Antineoplastic↗

PubMedDate not supplied

HER-2/neu receptor in prostate cancer development and progression to androgen independence.

Development of prostate cancer and progression to androgen-independent disease is correlated with increased expression of growth factors and receptors capable of establishing autocrine and/or paracrine growth-stimulatory loops. A thorough review was made of the current literature and recent abstract presentations at scientific meetings focusing on the role of the HER-2/neu (c-erbB2) receptor in prostate cancer and the potential clinical usefulness of its specific inhibitors. In the past 10 years, conflicting results on HER-2/neu expression in prostate cancer have been reported. More recently, four studies have shown experimental evidence of HER-2/neu in the development of prostate cancer and, more specifically, in the progression to a hormone-refractory clinical behavior. Furthermore, it has been proposed that HER-2 family and androgen receptors function synergistically in the absence of androgen, which suggests a cross-talk between the HER-2/neu and androgen receptor pathways. Finally, clinical trials are in progress in prostate cancer patients to test novel agents that selectively interfere with HER-2/neu activity.

Androgens↗

PubMedDate not supplied

External beam radiotherapy in bone metastatic prostate cancer: impact on patients' pain relief and quality of life.

Bone metastases are a severe problem in oncology, since they usually are associated with pain. External beam radiation therapy (EBRT) has been, for many years, an important component of the treatment regimen to relieve pain. We have performed a clinical study to evaluate the relationship of response to EBRT in terms of pain relief and improvement in quality of life (QoL). We were also interested in the incidence of acute toxicity with EBRT. We have prospectively evaluated 75 patients (median age 68 years, range 64-79 years) with bone metastases from prostate cancer treated with EBRT, radiographically documented from June 1999 to September 2000. Additional therapies in these patients included: second-line hormonal therapy (HT) in 20 patients, chemotherapy (CT) in 25 patients, biphosphonates in 45 patients. For all patients a pain and narcotic evaluation was done before entering the study. Assessment of response was carried out by evaluating pain relief. QoL was measured by using the EORTC QLQ-C30 questionnaire. Toxicity analysis was based on the ROTG grading system. Survival was calculated by Kaplan-Meier estimate from the start of EBRT treatment until the last follow-up or death. A total of 61 out of 75 patients (81%) experienced some type of pain relief after treatment. The complete response rate was 23%. No significant difference in the response rates was found between the group treated with EBRT alone versus the groups treated with EBRT + CT or EBRT + HT. We noted a significant improvement in some of the scales of the considered EORTC-QLQC30 questionnaire. As expected all treatment-related complications were either grade 1-2 acute or subacute and transitory in nature. The group treated with EBRT + CT experienced slightly higher toxicity rates. There were no treatment-related fatalities. Forteen patients of 61 (23%) responders was alive at 12 months. Our results confirm the ability of EBRT to relieve bony pain in the majority of the cancer patients treated as measured by prospective analysis of pain scales prior to and after EBRT. Minimal side effects were experienced and QoL improved as shown by the results of the specific questionnaire.

Aged↗