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Le Grazie di Ancona, Italy

Spitaleri G.,Istituto Europeo di Oncologia | Berardi R.,Clinica di Oncologia Medica | Pierantoni C.,Clinica di Oncologia Medica | De Pas T.,Istituto Europeo di Oncologia | And 8 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Purpose: L19-TNF is an armed antibody that selectively targets human TNF to extra domain B-fibronectin on tumour blood vessels. We performed a phase I/II first-in-man trial with L19-TNF monotherapy in metastatic solid cancer patients to study safety and signs of clinical activity. Methods: Six cohorts of patients were treated with increasing (1.3-13 μg/kg) doses of intravenous L19-TNF on day 1, 3, and 5 of repeated 3-weekly cycles, and 12 colorectal cancer patients were treated at 13 μg/kg. PK, antibody formation, changes in lymphocyte subsets, 5-HIAA plasma levels as well as safety and clinical activity were analysed. Results: Thirty-four patients received at least one L19-TNF dose. The serum half-life of L19-TNF at 13 μg/kg was 33.6 min, and maximum peak serum concentration was 73.14 μg/L. Mild chills, nausea and vomiting but no haemato- or unexpected toxicity were observed. Grade 3 lumbar pain in bone metastasis was the only dose-limiting toxicity found in one patient. Objective tumour responses were not detected. Transient stable disease occurred in 19 of 31 evaluable patients. Conclusions: Intravenous L19-TNF on day 1, 3, and 5 of a 3-weekly schedule was safe up to 13 μg/kg, but did not result in objective tumour responses. The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19-TNF possibly in combination with chemotherapy. © 2012 Springer-Verlag Berlin Heidelberg.

Lambertini M.,U.O. Oncologia Medica A | Boni L.,Centro Coordinamento Sperimentazioni Cliniche | Michelotti A.,U. O. Oncologia Medica I | Gamucci T.,Ospedale SS Trinita | And 11 more authors.
JAMA - Journal of the American Medical Association | Year: 2015

Importance Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. Objective To evaluate long-term results of LHRHa-induced ovarian suppression during breast cancer chemotherapy. Design, Setting, and Participants Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal women with stage I to III hormone receptor-positive or hormone receptor-negative breast cancer were enrolled. Last annual follow-up was June 3, 2014. Interventions Patients were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus triptorelin (LHRHa group). Main Outcomes and Measures The primary planned end pointwas incidence of chemotherapy-induced early menopause. Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). Results A total of 281 women (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6%(95%CI, 65.7%-80.3%) among the 148 patients in the LHRHa group and 64.0%(95%CI, 56.2%-72.8%) among the 133 patients in the control group (hazard ratio [HR], 1.28 [95%CI, 0.98-1.68]; P =.07; age-adjusted HR, 1.48 [95%CI, 1.12-1.95]; P =.006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95%CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6%[95%CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95%CI, 0.68-9.60]; P =.14; age-adjusted HR, 2.40 [95%CI, 0.62-9.22]; P =.20). Five-year DFS was 80.5%(95%CI, 73.1%-86.1%) in the LHRHa group and 83.7%(95%CI, 76.1%-89.1%) in the control group (LHRHa vs control: HR, 1.17 [95%CI, 0.72-1.92]; P =.52). Conclusions and Relevance Among premenopausalwomenwith either hormone receptor- positive or hormone receptor-negative breast cancer, concurrent administration of triptorelin and chemotherapy, compared with chemotherapy alone,was associated with higher long-term probability of ovarian function recovery, without a statistically significant difference in pregnancy rate. Therewas no statistically significant difference in DFS forwomen assigned to triptorelin and those assigned to chemotherapy alone, although study powerwas limited. © 2015 American Medical Association. All rights reserved.

Lambertini M.,U.O. Oncologia Medica 2 | Ferreira A.R.,University of Lisbon | Poggio F.,U.O. Oncologia Medica 2 | Puglisi F.,University of Udine | And 15 more authors.
Oncologist | Year: 2015

Background. We evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab. Materials and Methods. A total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models. Results. In the 202 trastuzumab-naive patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p =.131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p =.370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p =.045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p =.404). Patients with a trastuzumab-free interval (TFI) <6 months, visceral involvement, and hormone receptor-negative disease showed a worse OS compared with patients with aTFI of $6 months (29.5 vs. 48.3 months; p =.331), nonvisceral involvement (48.0 vs. 60.3 months;p =.270), and hormone receptor-positive disease (39.8 vs. 58.6 months; p =.003), respectively. Conclusion. Despite the inferior median PFS, trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients. © AlphaMed Press.

Sanna G.,Sandro Pitigliani Medical Oncology Unit | Fabi A.,IFO | Crivellari D.,Centro Of Riferimento Oncologico | Saracchini S.,Azienda Ospedaliera S Maria degli Angeli | And 11 more authors.
Tumori | Year: 2014

Methods: A subgroup analysis was carried out to report on the safety (primary endpoint) and efficacy (secondary endpoint) outcomes of patients recruited from Italian Centers.Results: A total of 278 patients were included. Median age was 57 years (range, 26-85), and ECOG performance status was 0 or 1 in 96% of the patients. Bevacizumab was predominantly combined with a taxane monotherapy: paclitaxel (41.4%), docetaxel (21.9%), or a taxane-based combination therapy (12.2%). The most frequent grade.3 adverse events previously associated with bevacizumab were hypertension (3.2%), proteinuria (2.9%), and cardiac disorders (0.7%). Median time to progression was 10.9 months. Median overall survival was 29.9 months, and 1-year survival probability was 85%. Objective responses were observed in 62.6% of the patients, and an additional 30% achieved stable disease.Conclusions: Results from the study support the safety and efficacy of bevacizumab in combination with chemotherapy for the treatment of locally recurrent/metastatic breast cancer in the context of routine oncology practice in Italy.Aims and background: The ATHENA international study investigated the safety and efficacy of bevacizumab plus first-line chemotherapy in locally recurrent/metastatic breast cancer in routine oncology practice. The present paper focuses on the outcomes of the Italian cohort of the study.

Insulin-like growth factor receptor 1 (IGF-1R) with its ligands and intracellular pathway is involved in cell growth and survival control. Many studies have shown how IGF-1R is over-expressed in various tumor cell lines and histological samples. In recent years many trials have been conducted investigating IGF-1R as a possible cancer therapy, with major efforts focusing on the use of monoclonal antibodies and small molecules directed against the IGF-1R-driven pathway. Several drugs are currently under intense investigation and in different experimental phases. Available data suggest that this class of drugs is well tolerated with mild to moderate side effects, when used alone or in combination with other therapeutic agents. The efficacy profile seems to be promising. However, further studies are needed to define the exact role of IGF-1R inhibitors in clinical practice.

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