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Meldola, Italy

Maltoni M.,Palliative Care Clinic | Scarpi E.,Biostatistics and Clinical Trials Unit | Pittureri C.,Palliative Care Unit | Martini F.,Palliative Care Unit | And 7 more authors.

Purpose. Predicting prognosis in advanced cancer aids physicians in clinical decision making and can help patients and their families to prepare for the time ahead. Materials and Methods. This multicenter, observational, prospective, nonrandomized population-based study evaluated life span prediction of four prognostic scores used in palliative care: the original Palliative Prognostic Score (PaP Score), a variant of PaP Score including delirium (DPaP Score), the Palliative Performance Scale, and the Palliative Prognostic Index. Results. A total of 549 patients were enrolled onto the study. Median survival of the entire group was 22 days (95% confidence intervals [95% CI] = 19 -24). All four prognostic models discriminated well between groups of patients with different survival probabilities. Log-rank tests were all highly significant (p <.0001). The PaP and D-PaP scores were the most accurate, with a C index of 0.72 (95% CI = 0.70-0.73) and 0.73 (95% CI = 0.71-0.74), respectively. Conclusion. It can be confirmed that all four prognostic scores used in palliative care studies accurately identify classes of patients with different survival probabilities. The PaP Score has been extensively validated and shows high accuracy and reproducibility in different settings. © AlphaMed Press. Source

Fabbri F.,Biosciences Laboratory | Brigliadori G.,Biosciences Laboratory | Carloni S.,Biosciences Laboratory | Ulivi P.,Biosciences Laboratory | And 4 more authors.

BACKGROUND. The efficacy of current therapy for hormone-refractory prostate cancer is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of different antitumor drug combinations in hormone-resistant prostate cancer (HRPC) cell lines. METHODS. The activity of docetaxel (Doc), cisplatin (Cis), oxaliplatin (Oxa), SN-38 and ST1481, singly or in combination, was assessed in different HRPC cell lines (PC3, parental DU145 and taxane-resistant DU145-R) by SRB test. Apoptosis was evaluated by TUNEL and ANN-V assays. Extrusion pump activity was studied by Hoechst 33342 assay, while gene expression related to drug efflux mechanisms and DNA damage repair was analyzed by RT-PCR. RESULTS. Doc induced a high cytocidal effect in the HRPC cells, whereas Cis, Oxa, SN-38 and ST1481 exerted prevalently cytostatic activity. Doc followed by ST1481 proved to be the most effective drug sequence among those investigated, producing an important synergistic effect (R.I. from 2.0 to 5.2) in all the tested cell lines. Moreover, this sequence induced a significant downregulation of xenobiotic extrusion pump and DNA damage repair gene expression. ST1481 synergistically increased the cytocidal effect of Doc, probably through a downregulation of extrusion pump activity and DNA damage repair-related genes. CONCLUSIONS. Our results show that the Doc → ST1481 sequence effectively reduces the cancer cell population and restores Doc activity in taxane-resistant HRPC, indicating its potential usefulness as first- or second-line treatment of hormone-refractory prostate cancer. © 2009 Wiley-Liss, Inc. Source

Cardoso F.,Jules Bordet Institute | Cardoso F.,Champalimaud Cancer Center | Canon J.-L.,Grand HOpital de Charleroi | Amadori D.,IRST | And 9 more authors.

Background: This exploratory study assessed the safety, pharmacokinetics, and antitumor activity of sunitinib combined with docetaxel and trastuzumab. Methods: Patients with unresectable, locally recurrent or metastatic human epidermal growth factor receptor 2 (HER2)+ breast cancer received sunitinib plus docetaxel and trastuzumab. Sunitinib was administered at 37.5 mg/day for 2 weeks on treatment followed by 1 week off (Schedule 2/1). The primary endpoint was safety; secondary endpoints included pharmacokinetics and antitumor activity. Results: Twenty-six patients enrolled; 24 received at least one dose of sunitinib plus docetaxel and trastuzumab, and one patient received one dose of docetaxel and trastuzumab only. These 25 treated patients were evaluable for safety. Twenty-three patients discontinued the study, primarily due to disease progression. The planned dose of sunitinib was maintained in 10 patients and reduced at least once to 25 mg/day in 14 patients. The most common grade 3/4 non-hematologic adverse events were fatigue/asthenia (28%), diarrhea (16%), stomatitis (12%), vomiting (8%) and dyspnea (8%). Neutropenia was reported in all 24 evaluable patients; most events were grade 4. Three grade 1-3 cardiac adverse events occurred. Sunitinib and docetaxel levels were consistent with known single-agent levels, suggesting that there were no clinically relevant drug-drug interactions. Of 22 evaluable patients, 16 (73%) experienced an objective response (all confirmed partial responses). Conclusions: Sunitinib combined with docetaxel and trastuzumab had an acceptable toxicity profile and showed preliminary antitumor activity as first-line treatment for metastatic HER2+ breast cancer. © 2012 Elsevier Ltd. Source

Lorenzini C.,University of Bologna | Lamberti C.,University of Bologna | Aquilina M.,IRST
Computing in Cardiology

The aim of this retrospective study was to detect early cardiotoxicity by speckle tracking analysis. We analyzed 2D and 3D echocardiographic datasets (2DE and 3DE) in 65 patients treated for breast cancer with anthracycline and trastuzumab. We compared the temporal variations of the left ventricular ejection fraction (LVEF) obtained analyzing 2D and 3D datasets and of the strain values computed before, during and after chemotherapy administration. In addition, in a subgroup of 45 patients a complete echocardiographic examination was performed 6 months after completion of therapy. Cardiotoxicity onset definition varies depending on the method used to compute LVEF (16.9% by 2DE and 50.8% by 3DE). Thirty-three patients developed cardiotoxicity. Nine of them showed a reduction of longitudinal and radial strain values before LVEF reduction at the 16th week. Through 3D speckle tracking analysis early diagnosis of the cardio-toxicity onset seems achievable allowing the planning of cardio protective therapy without interrupting chemotherapy administration. © 2015 CCAL. Source

Fabbri F.,Biosciences Laboratory | Zoli W.,Biosciences Laboratory | Carloni S.,Biosciences Laboratory | Ulivi P.,Biosciences Laboratory | And 6 more authors.
Journal of Cellular Physiology

The efficacy of therapy for hormone-refractory prostate cancer (HRPC) is still unsatisfactory and new agents and therapeutic modalities are needed. The aims of the present work were to examine the in vitro activity and mechanisms of action of doxorubicin (DX), pegylated liposomal DX (PLDX), and non-pegylated liposomal DX (NPLDX) in DU145 and taxane-resistant DU145-R HRPC cell lines. Drug activity and incorporation, apoptosis, and expression of cell death-related markers were evaluated by SRB test, cytofluorimetric assays, and Western blot, respectively. Among the different DX formulations, NPLDX showed the highest cytotoxic activity in both cell lines, with more than 50% of apoptotic cells at only 1/10 of the plasma peak concentration after 72h exposure. Anthracyclines, in particular NPLDX, were highly concentrated in the Golgi apparatus. Moreover, a significant increase was observed in the expression of CD95 receptor, GD3 ganglioside and, caspase-2 and -8 active forms in both cell lines followed by caspase-3 activation and mitochondrial membrane depolarization. The Golgi apparatus, probably acting as a stress sensor, intensified the conventional apoptotic mechanism induced by anthracyclines. Our data support the hypothesis that organelle-dependent initiation of cell death other than that induced by mitochondria and nucleus is a research area worthy of pursuing and suggest that the Golgi apparatus could be an ideal target for anti-cancer therapy. Of note, the activity of NLPDX in taxane-resistant DU145-R cells warrants further evaluation as second-line treatment of advanced HRPC after taxane failure. © 2011 Wiley-Liss, Inc. Source

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