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Conteduca V.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Aieta M.,Centro Of Riferimento Oncologico Della Basilicata Irccs | Amadori D.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | De Giorgi U.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Critical Reviews in Oncology/Hematology | Year: 2014

Neuroendocrine differentiation (NED) secondary to androgen deprivation therapy (ADT) may be frequent in various stages of prostate cancer (PC), particularly in castration-resistant PC (CRPC). NED generally involves more aggressive PC clinical behavior and an unfavorable prognosis. The identification of neuropeptides secreted by NE cells and of different proliferative and anti-apoptotic pathways has led to attention being focused on probable diagnostic targets and therapeutic options for a subtype of PC. Emerging evidence suggests that the acquisition of epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) phenotype are associated with the development of NED in PC, responsible for a complex interaction between ADT, the onset of CRPC and NED, in which EMT and CSC could play a central role, providing potential therapeutic targets. In this article, we review the pathogenetic, prognostic and predictive significance of NED in human PC, providing an insight into innovative agents capable of treating and perhaps preventing NED occurrence. © 2014 Elsevier Ireland Ltd.

Di Lorenzo G.,University of Naples Federico II | Buonerba C.,University of Naples Federico II | Ferro M.,Italian National Cancer Institute | Calderoni G.,Centro Of Riferimento Oncologico Della Basilicata Irccs | And 5 more authors.
Expert Opinion on Biological Therapy | Year: 2014

Penile cancer is a rare disease, with an incidence that is higher in less developed countries and is in the range of 1 - 10 per 100000 men worldwide. Early diagnosis is essential for cure, as 5 year cancer-specific survival is 90 - 100 % in patients with intraepithelial neoplasms and in those with low-grade superficial tumors without lymphovascular invasion, but it drops to 30% in men with multiple mobile or bilateral inguinal lymph nodes. The EGFR family plays a major role in penile cancer biology, with distinct receptors being involved in HPV-positive and -negative tumors. A number of anti-EGFR agents were used in penile cancer patients outside the context of a clinical trial, mainly as a salvage treatment after failure of first-line chemotherapy. A total of 28 patients received anti-EGFR monoclonal antibodies, with 50% of them showing a response to treatment, and a median PFS of ∼ 3 months. The rarity of the disease poses great challenge in terms of education and awareness of the general population, planning of preventive measures on a large scale, as well as conduction of prospective trials and approval of high-cost biological therapy. © 2014 Informa UK, Ltd.

Sonpavde G.,Comprehensive Cancer Center | Pond G.R.,McMaster University | Choueiri T.K.,Dana-Farber Cancer Institute | Mullane S.,Dana-Farber Cancer Institute | And 11 more authors.
European Urology | Year: 2016

Background Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). Objective To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Design, setting, and participants Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Interventions Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Outcome measurements and statistical analysis Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Results and limitations Data were available from eight trials including 370 patients; two trials (n = 109) evaluated single-agent chemotherapy with docetaxel (n = 72) and cremophor-free paclitaxel (n = 37), and six trials (n = 261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n = 99 and n = 24), paclitaxel-cyclophosphamide (n = 32), paclitaxel-ifosfamide-nedaplatin (n = 45), docetaxel-ifosfamide-cisplatin (n = 26), and paclitaxel-epirubicin (n = 35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p = 0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Conclusions Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination chemotherapeutic regimens for the salvage therapy of advanced UC. Patient summary This retrospective study suggests that a combination of chemotherapy agents may extend survival compared with single-agent chemotherapy in selected patients with metastatic urothelial cancer progressing after prior chemotherapy. © 2015 European Association of Urology.

Conteduca V.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori | Zamarchi R.,Istituto Oncologico Veneto | Rossi E.,University of Padua | Condelli V.,Centro Of Riferimento Oncologico Della Basilicata Irccs | And 2 more authors.
Future Oncology | Year: 2013

Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia, but its actual utility remains among the fastest growing research fields in oncology. © 2013 Future Medicine Ltd.

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