Michele Aieta

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Emilia-Romagna, Italy

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Publications (38)205.53 Total impact

  • Alfredo Tartarone, Rosa Lerose, Michele Aieta
    Annals of Oncology 04/2014; · 7.38 Impact Factor
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    ABSTRACT: Objective Lymphopenia is associated with toxicity and outcomes in several cancer types. We assessed the association between pre-treatment lymphopenia, toxicity, and clinical outcomes in elderly patients with metastatic renal cell cancer (mRCC) treated with first-line sunitinib. Prognostic factors in these patients were also evaluated. Patients and methods We reviewed the clinical records of 181 patients with mRCC aged ≥ 70 years treated with first-line sunitinib in 17 Italian Oncology Units from February 2006 to September 2011. Baseline lymphopenia was defined as lymphocyte counts < 1000/μL. Results Twenty-nine (16%) patients had a baseline lymphocyte count < 1000/μL (group A) and 152 (84%) patients had a lymphocyte count ≥ 1000/μL (group B). Although no differences between the two groups were reported in terms of overall response rate (P = 0.207), dose reductions (P = 0.740), discontinuation due to adverse events (P = 0.175) or overall incidence of grade 3–4 toxicities (P = 0.112), more patients in the lymphopenia group had grade 3–4 neutropenia (P = 0.017), grade 3–4 thrombocytopenia (P = 0.017) and grade 3–4 diarrhea (P = 0.006). In multivariate analysis, performance status and Heng score were predictors of progression-free survival (P = 0.015 and P = 0.0006, respectively), while performance status, Heng score, and lymphopenia were found to be significantly associated with overall survival (P = 0.007, P < 0.0001 and P = 0.023, respectively). Conclusions Sunitinib appears to be safe and active in elderly patients with lymphopenia. Lymphocyte count is an independent prognostic factor for overall survival in elderly patients with mRCC treated with first-line sunitinib.
    Journal of Geriatric Oncology 01/2014; · 1.12 Impact Factor
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    ABSTRACT: The efficacy of high-dose chemotherapy (HDC) and autologous hemopoietic progenitor cell transplantation (AHPCT) for breast cancer (BC) patients (pts) has been an area of intense controversy among the medical oncology community. Aim of this study is to assess toxicity and efficacy of this procedure in a large cohort of high-risk primary breast cancer (HRPBC) who underwent AHPCT in Italy. 1183 pts receiving HDC for HRBC (> 3 positive nodes) were identified in the Italian registry. Median age was 46 years, 62% of patients were pre menopausal at treatment, 60.1% had an endocrine responsive tumours and 20.7% had a HER2+ tumour. Median number of positive LN at surgery was 15 with 71.5% of patients having >10 positive nodes. 73% received alkylating agent-based HDC as a single procedure while 27% received epirubicin or mitoxantrone-containing HDC, usually within a multi-transplant program. Source of stem cells was peripheral blood in the vast majority of pts. Transplant related mortality was 0.8 %, while late cardiac and secondary tumour-related mortality were around 1% overall. With a median follow up of 79 months, median disease-free and overall survival (OS) in the entire population were 101 and 134 months, respectively. Subgroup analysis demonstrated that OS was significantly better in endocrine responsive tumours and in patients receiving multiple transplant procedures. HER2 status did not affect survival probability Size of primary tumor and number of involved LN negatively affected OS. Adjuvant HDC with AHSCT has low mortality rate and provides impressive long-term survival rates in patients with HRPBC. Our results suggest that this treatment modality should be proposed in selected HRBC patients and further investigated in clinical trials.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2013; · 3.15 Impact Factor
  • European Urology 11/2013; · 10.48 Impact Factor
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    ABSTRACT: 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.
    Future Oncology 09/2013; 9(9):1337-52. · 3.20 Impact Factor
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    ABSTRACT: The discovery of several molecular alterations that underlie non-small cell lung cancer (NSCLC) pathogenesis has led to the development of targeted therapies. In particular, gefitinib and erlotinib have become the standard of care in patients harboring epidermal growth factor receptor mutations, while crizotinib showed an impressive efficacy in patients with ALK-positive NSCLC. Nevertheless, the occurrence of clinical resistance limits the long term results of these novel agents. The identification of the molecular mechanisms responsible for acquired resistance to targeted therapy is crucial in order to pursue the creation of rational strategies to overcome resistance. In the current review, we will focus on the acquired resistance mechanisms to EGFR-TKIs and crizotinib and the therapeutic strategies currently under study to overcome resistance.
    Lung cancer (Amsterdam, Netherlands) 06/2013; · 3.14 Impact Factor
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    ABSTRACT: Aim: This study aimed to identify predictive/prognostic factors in castration-resistant prostate cancer patients treated with cabazitaxel. Patients & methods: Patients were enrolled from March 2011 to December 2011 in an international expanded access program. In January 2012, when cabazitaxel became commercially available, a prospective study was initiated at University Federico II of Naples and at Rionero in Vulture Hospital. Results: Forty-seven patients were enrolled in this study. Patients received a median of nine cycles of cabazitaxel. Median progression-free survival was 7.0 months (95% CI: 5.7-8.0). Seventeen patients were still alive at the time of the analysis, with a median overall survival of 14 months (95% CI: 11-16). At multivariate analysis, a higher Gleason score (≥8) appeared to be associated with prolonged progression-free survival (hazard ratio: 0.36; 95% CI: 0.18-0.72); however, the higher Gleason score showed no statistical impact on overall survival. Conclusion: We hypothesize that the Gleason score has the potential to be incorporated in the clinical decision-making process for definition of treatment strategy in docetaxel-pretreated castration-resistant prostate cancer patients. We encourage further experimentation in this setting.
    Future Oncology 06/2013; 9(6):889-897. · 3.20 Impact Factor
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    ABSTRACT: An interesting and reciprocal association between the metabolic syndrome and prostate cancer has been identified. Metabolic alterations, such as hyperinsulinemia, increased levels of insulin growth factor-1, and insulin resistance could be on the basis of development and progression of many tumors, including prostate cancer, and changes in body composition, in turn, can represent some side effects of androgen deprivation therapy and novel drugs, such as mammalian target of rapamycin inhibitors. This review evaluates this interrelation between metabolic syndrome and prostate tumor scanning in many clinical and preclinical epidemiological studies and describes possible pathogenetic biological mechanisms. Finally, this article discusses feasible clinical implications for the management, prevention, diagnosis, prognosis, and treatment of patients affected by metabolic syndrome and prostate cancer, with particular attention to the metformin action.
    Clinical Genitourinary Cancer 05/2013; · 1.43 Impact Factor
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    ABSTRACT: Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy.
    International Journal of Molecular Sciences 01/2013; 14(10):19731-19762. · 2.46 Impact Factor
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    ABSTRACT: Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor. Our experience confirms that inhibition of angiogenic factors to treat cancer is a novel challenge for the oncologist and requires the cardiologist's support.
    Future Oncology 01/2013; 9(1):127-33. · 3.20 Impact Factor
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    ABSTRACT: Background There are no data on the patterns of care and outcome of elderly patients with mRCC treated with sunitinib. In a retrospective study, we assessed the routine use of first-line sunitinib in mRCC patients aged ≥ 70 years. Patients and Methods We reviewed the clinical files of 185 patients aged >70 years with mRCC treated with first-line sunitinib in seventeen Italian Oncology Units from February 2006 to September 2011. One hundread twenty-three patients (66.5%) received a standard 50 mg/d 4 wk on/2 wk off regimen (SR), and 62 patients (33.5%) received an adapted regimen (AR) consisting in 37.5 mg/d 4 wk on/2 wk off in 67.7% of cases. Results Median age was 74 years. Patients treated with an AR were older than those treated with the SR (P <.0001). In the overall population, the median progression-free survival (PFS) was 11 months, and the median overall survival (OS) was 25.5 months. Grade 3-4 toxicities occurred in 70.7% of SR and 51.6% of AR, respectively; dose reductions were required in 66.7% and 41.9%, respectively; discontinuations due to therapy-related adverse events occurred in 20.3% and 24.2%, respectively. In multivariate analysis, only performance status and the Heng score were predictors of either PFS or OS. Conclusions Sunitinib is active and feasible in elderly patients with mRCC. A sunitinib AR could be considered as an option in selected older mRCC patients. The optimal treatment of frail patients with mRCC remains to be established.
    Clinical Genitourinary Cancer 01/2013; · 1.43 Impact Factor
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    ABSTRACT: : An understanding of the activated protein signaling architecture in non-small-cell lung cancer (NSCLC) is of critical importance to the development of new therapeutic approaches and identification of predictive and prognostic biomarkers for patient stratification. : We used reverse-phase protein microarrays to map the activated protein signaling networks of 47 NSCLC tumors, 28 of which were node negative, which were subjected to tumor cellular enrichment using laser capture microdissection. The phosphorylation/cleavage levels of 111 key signaling proteins and total levels of 17 proteins were measured for broadscale signaling analysis. : Pathway activation mapping of NSCLC revealed distinct subgroups composed of epidermal growth factor receptor (ERBB1), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ERBB4), v-akt murine thymoma viral oncogene homolog 1- mammalian target of rapamycin (AKT-mTOR), protein kinase, AMP-activated, alpha 2 catalytic subunit (AMPK), and autophagy-related signaling, along with transforming growth factor-beta-signaling protein 1 (SMAD), insulin-line growth factor receptor (IGFR), rearranged during transfection proto-oncogene (RET), and activated CDC42-associated kinase (ACK) activation. Investigation of epidermal growth factor receptor (EGFR)-driven signaling identified a unique cohort of tumors with low EGFR protein expression yet high relative levels of phosphorylated EGFR and high EGFR total protein with low relative levels of phosphorylation. Last, mapping analysis of patients with NSCLC with N0 disease revealed a pilot pathway activation signature composed of linked epidermal growth factor receptor family (HER)-AMPK-AKT-mTOR signaling network along with focal adhesion kinase- LIM domain kinase-1 (FAK-LIMK) and janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathways that correlated with short-term survival and aggressive disease. : Functional protein pathway activation mapping of NSCLC reveals distinct activation subgroups that are underpinned by important therapeutic targets and that patients with early-stage node negative disease and poor prognosis may be identified by activation of defined, biochemically linked protein signaling events. Such findings, if confirmed in larger study sets, could help select and stratify patients for personalized targeted therapies.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2012; 7(12):1755-66. · 4.55 Impact Factor
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    ABSTRACT: Gonadotropin-releasing hormone agonists (GnRH) play an important role in the treatment of prostate cancer, improving significantly overall survival. GnRH agonists belong to androgen deprivation therapy (ADT) together with surgical castration and, recently, GnRH antagonists. ADT has several side effects, such as sexual dysfunction and osteoporosis. Recently, changes in body composition, obesity, insulin resistance, hyperglycemia, dyslipidemia, and hypertension have emerged as complications of ADT, perhaps responsible for cardiovascular events, but discussion is still open. Since the majority of men with prostate cancer die of conditions other than their malignancy, recognition of these adverse effects is important. This review serves to focus attention on the pathogenetic mechanisms of ADT-related cardiovascular toxicity with also reference to the possible direct role of GnRH agonist on the cardiac receptors. Furthermore, this paper would generate recommendations for the management of patients treated with GnRH agonists balancing the potential benefits against the possible risks in prostate cancer men.
    Critical reviews in oncology/hematology 10/2012; · 5.27 Impact Factor
  • Alfredo Tartarone, Rosa Lerose, Michele Aieta
    Therapeutic drug monitoring 10/2012; 34(5):604. · 2.43 Impact Factor
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    ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Metastatic or locally advanced squamous cell carcinoma of the penis (SCCP) is generally incurable, but it can be palliated with systemic chemotherapy. Two retrospective studies, involving <10 patients each, showed that cisplatin plus continuous infusion of 5-fluorouracil (5-FU) may be effective and well tolerated. Cisplatin, methotrexate and bleomycin, cisplatin and irinotecan and taxanes can also play an important role for patients with locally advanced/metastatic SCCP. Finally, anti-EGFR therapy may also be effective in advanced SCCP. Although cisplatin plus continuous infusion of 5-FU is widely used in clinical practice for palliation of SCCP, toxicity and efficacy data regarding this schedule include a total of 14 patients with SCCP, treated more than two decades ago. In our retrospective study, cisplatin plus continuous infusion of 5-FU was used for palliative purposes in a homogenous sample of 25 patients with SCCP. Partial responses and stable disease were observed in 8 (32%) and 10 (40%) patients, respectively, with a median progression-free survival of 20 weeks. Neutropenia was the most important grade 3-4 side effect observed, occurring in 20% of patients. These data provide confirmation that such a combination regimen is moderately effective and well tolerated in patients with SCCP. OBJECTIVE: •  To investigate the activity and toxicity of 5-fluorouracil (5-FU) as a first-line treatment in metastatic squamous cell carcinoma of the penis (SCCP). METHODS: •  The medical records of 78 patients with SCCP treated between January 2000 and June 2011 at the four participating centres were reviewed. •  Data regarding patients treated with first-line 5-FU were extracted. •  Patients were included in the study if radiological reports were available for determination of response and progression-free survival (PFS) according to response evaluation criteria in solid tumours (RECIST) 1.1. RESULTS: •  Between January 2000 and June 2011, 25 patients were treated with i.v. cisplatin on day 1 followed by 5-FU as a continuous 24-h infusion for 4 days every 3 weeks until disease progression or unacceptable toxicity. Partial responses and stable disease were observed in eight (32%) and 10 (40%) patients, respectively, with a disease control rate of 72%. •  Severe neutropenia was the most important grade 3-4 side effect observed, occurring in 20% of patients. •  The median (interquartile range [IQR]) PFS was 20 (11-20) weeks and the median (IQR) overall survival (OS) was 8 (7-12) months. CONCLUSION: •  5-FU is associated with a moderate response rate and is well tolerated in patients with metastatic SCCP.
    BJU International 09/2012; · 3.05 Impact Factor
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    ABSTRACT: Background:Recently, we developed an apoptotic assay for expanding the monitoring capabilities of the circulating tumour cells (CTC) test during therapy. An automated platform for computing CTCs was integrated with a mAb (M30) targeting a neoepitope disclosed by caspase cleavage at cytokeratin 18 in early apoptosis; we showed that live CTCs were associated with progression, consistent with enhanced cell migration and invasion. The test was first applied here to mRCC.Methods:Live/apoptotic CTCs changes were measured in mRCC patients receiving first-line Sunitinib and compared with circulating endothelial cell (CEC) levels.Results:The presence of EpCAM-positive, live CTCs predicts progression in individual mRCC patient, being associated with distant metastasis under first-line Sunitinib. Synchronous detection of CTCs and CEC levels discloses for the first time an association between their dynamic changes and outcome: a rapid increase of the CEC number as early as the first cycle of therapy is associated with CTC decrease in non-progressed patients, whereas a delayed response of CECs is related to higher CTC values in the progressed group indicating treatment failure.Conclusion:We demonstrated that a delayed response to antiangiogenic treatment indicated by persistent detection of CECs correlates with persistent live CTCs and more aggressive disease.
    British Journal of Cancer 09/2012; 107(8):1286-94. · 5.08 Impact Factor
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    ABSTRACT: The median survival of women with metastatic breast cancer (MBC) is 18-24 months, and fewer than 5% are alive and disease free at 5 years. We report toxicity and survival in a cohort of MBC patients receiving high-dose chemotherapy (HDC) with autologous hematopoietic SCT (AHSCT) in Italy between 1990 and 2005. Data set for survival analysis has been obtained for 415 patients. Clinical parameters including probability of transplant-related mortality (TRM), PFS and OS. With a median follow-up of 27 months (range 0-172), OS and PFS at 5 and 10 years in the whole population were 47/23 and 32/14%, respectively. A total 239 patients are alive with a median follow-up of 33 months (range 2-174). Survival was significantly more pronounced in patients harboring hormone receptor positive tumors (P=0.028), without visceral metastases (P=0.009) and in women with chemosensitive disease (P<0.0001). Sixty eight patients (20.4%) who received HDC in partial response, stable or progressive disease underwent conversion to CR. TRM was 2.5% overall and 1.3% since 2000. Our findings suggest that could be a role for HDC and AHSCT in delaying disease progression and possibly cure a subset of MBC patient harboring chemosensitive tumors.Bone Marrow Transplantation advance online publication, 6 August 2012; doi:10.1038/bmt.2012.149.
    Bone marrow transplantation 08/2012; · 3.00 Impact Factor
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    ABSTRACT: Mutations of epidermal growth factor receptor 1 (EGFR) gene occur in about 15 % of all NSCLCs in Western Europe and are frequently located in exons 19 and 21, being associated with high sensitivity to EGFR tyrosine kinase inhibitors (TKIs). By contrast, exon 20 insertions account for up to 10 % of all EGFR mutations and are correlated to EGFR TKI resistance. Herein, we describe a novel mutation in EGFR exon 20 in a female non-smoker bearing a lung adenocarcinoma, characterized by the insertion of a nucleotide triplet GTT, which translates into a protein with an additional Valine between Proline 772 and Histidine 773 (p.P772_H773insV-c.2316_2317insGTT). The patient was treated with cisplatin/pemetrexed 1st-line and docetaxel 2nd-line chemotherapies, reporting a prolonged disease stabilization of 25 months. The identification and the biological and clinical characterization of novel EGFR mutations represent a prerequisite for their wide use as predictive biomarkers for personalized therapy in NSCLC.
    Medical Oncology 07/2012; · 2.14 Impact Factor
  • Alfredo Tartarone, Rosa Lerose, Michele Aieta
    New England Journal of Medicine 05/2012; 366(18):1739; author reply 1739-40. · 51.66 Impact Factor
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    ABSTRACT: Breast cancer usually metastasizes towards the lymph nodes, lung, bone, liver or brain; metastatic gastrointestinal involvement is rare and anal metastases are extremely rare. Necroscopic studies report a 6-18% incidence of extra-hepatic gastrointestinal metastases, and the most frequent sites of the GI tract involved are the stomach and the small intestine. We report a case with anal metastasis from breast cancer and a review of the associated literature.
    Future Oncology 03/2012; 8(3):333-6. · 3.20 Impact Factor

Publication Stats

243 Citations
44 Downloads
2k Views
205.53 Total Impact Points

Institutions

  • 2013
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 2006–2013
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Department of Oncology and Hematology
      Giovanni Rotondo, Apulia, Italy
  • 2009–2012
    • CRO Centro di Riferimento Oncologico di Aviano
      • Division of Medical Oncology A
      Aviano, Friuli Venezia Giulia, Italy