Publications by authors named "Danilo Galizia"

17 Publications

  • Page 1 of 1

Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy.

Vaccines (Basel) 2021 Mar 8;9(3). Epub 2021 Mar 8.

Translational Oncology, ARCO Foundation, 12100 Cuneo, Italy.

Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients' outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39).
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http://dx.doi.org/10.3390/vaccines9030235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999072PMC
March 2021

MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer.

ESMO Open 2020 10;5(5):e000937

Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy. Electronic address:

Purpose: Overexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer.

Methods: miR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype.

Results: Baseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype.

Conclusions: Our findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer.
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http://dx.doi.org/10.1136/esmoopen-2020-000937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597498PMC
October 2020

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study.

Cancers (Basel) 2020 Jan 31;12(2). Epub 2020 Jan 31.

Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.

Background: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab.

Methods: MCT was defined as an asymptomatic absolute decrease in LVEF of ≥ 10 percentage units to >50%. Treatment consisted of enalapril 2.5 mg bid and carvedilol 3.75 mg bid, which were up-titrated to 10 mg bid for the enalapril and 6,25 mg bid of carvedilol. In patients receiving study drug, the primary study end-point was LVEF recovery, which was defined as a post-trastuzumab LVEF returning to no less than -5 percentage points of the baseline value.

Results: 103 patients were enrolled, 100 started trastuzumab, and 98 completed the planned treatment. Sixteen patients (16%) had MCT and received study drugs until trastuzumab completion. None of these patients achieved a post-trastuzumab LVEF recovery. Nevertheless, treated patients had significantly higher median LVEF recovery from nadir to post-trastuzumab LVEF in (8% points vs. 4% points, respectively, p = 0.004), resulting in no difference in post-treatment LVEF values compared to patients without MCT.

Conclusion: Treatment of MCT with ACEis and BB allows faster LVEF recovery from nadir values and should be further studied in this setting.
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http://dx.doi.org/10.3390/cancers12020327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072182PMC
January 2020

How I treat squamous ENT cancer.

ESMO Open 2019 16;4(Suppl 2):e000542. Epub 2019 Jul 16.

Department of Medical Oncology, S Croce and Carle Teaching Hospital, Cuneo, Italy.

The definition of 'head and neck cancer' (HNC) identifies squamous cell carcinoma arising from the pharynx, the larynx and the oral cavity. Most of them are induced by smoking and alcohol abuse, but tumours arising in the nasopharynx and in the oropharynx may be virus induced, Epstein-Barr virus and human papillomavirus, respectively. Medical oncologists are involved in HNC in locally advanced disease and in relapsed/metastatic disease not suitable for salvage radiotherapy or surgery. A close cooperation with surgeons and in particular with radiation oncologists is required in the first situation. The second situation is almost completely responsibility of medical oncologists while surgeons and radiation oncologists are involved in specific situations requiring palliative treatments. Interventions in locally advanced diseases change according to the goal of treatment. Indeed, the target may be the cure of patients unresectable disease or that have refused surgery, the adjuvant treatment of resected diseases at high risk of relapse, or organ preservation, which means sparing demolitive surgery requiring severe functional impairment, such as definitive laryngectomy. In all these situations, a close cooperation between the medical oncologist and the radiation oncologist is mandatory. Treatment of relapsed/metastatic disease is rapidly changing due to the development of immunotherapy. Although the results of immune checkpoint inhibitors in HNC are less impressive than in other tumours such as melanoma or lung cancer, these drugs are effective and allow for long-term survivors that were not expected with chemotherapy and target therapy. In particular, first-line treatment will change soon. Indeed, due to the result of a large randomised trial, immunotherapy will replace the combination of cisplatin, fluorouracil and cetuximab at least in a large proportion of patients.
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http://dx.doi.org/10.1136/esmoopen-2019-000542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6735671PMC
July 2019

What is the best pharmacotherapeutic strategy for HER-2 positive breast cancer?

Expert Opin Pharmacother 2019 01 6;20(1):5-9. Epub 2018 Nov 6.

c Investigational and Clinical Oncology , Candiolo Cancer Institute-FPO, IRCCS , Candiolo , Italy.

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http://dx.doi.org/10.1080/14656566.2018.1543406DOI Listing
January 2019

Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide.

Clin Transl Radiat Oncol 2018 Aug 13;12:47-52. Epub 2018 Aug 13.

Radiation Oncology, IRCCS S. Martino, IST National Cancer Research Institute and University, Genova, Italy.

Introduction And Background: Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors.

Methods/design: In this open label, multi-center, single-arm, Phase Ib/II, R/M-HNC patients pretreated with at least one line of therapy containing platinum, fluorouracil, and cetuximab will receive a daily metronomic dose of 50 mg cyclophosphamide without a drug-free break, 10 mg/kg avelumab on day 1 and every other week until progression, and a single fraction of 8 Gy radiotherapy on day 8.

Discussion: The treatment protocol aims to reverse immune evasion of the tumor through a radiotherapy-induced self-vaccination effect, suppression of CD4+ CD25+ FoxP3+ regulatory T-cell function by metronomic cyclophosphamide, and effector T-cell reactivation owing to the inhibition of the PD-1-PD-L1 axis by avelumab.The immunologic interplay induced by the proposed combined treatment may theoretically improve the activity of avelumab without increasing its toxicity profile.Finally, an ancillary translational study will be extended to all the patients' population.

Trial Registration: EudraCT n. 2017-000353-39.
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http://dx.doi.org/10.1016/j.ctro.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107891PMC
August 2018

Self-evaluation of duration of adjuvant chemotherapy side effects in breast cancer patients: A prospective study.

Cancer Med 2018 09 20;7(9):4339-4344. Epub 2018 Jul 20.

Investigational and Clinical Oncology (INCO), Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.

Background: We recently reported that self-evaluation of the incidence and severity of treatment-related side effects (TSEs) using a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0-based questionnaire was feasible and more informative than doctor reports in patients undergoing standard adjuvant chemotherapy for operable breast cancer. Here, we compare self- and doctor-evaluated day of onset and duration of TSEs in the same population.

Patients And Methods: Six hundred and four patients were enrolled at 11 sites in Italy. CTCAE v4.0 definitions of grade of severity of nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea were translated into Italian and rephrased. Questionnaires were administered after the first and third chemotherapy cycles. At each time-point, information on TSEs was extracted from the medical charts and compared to patient questionnaires.

Results: A total of 594 and 573 paired patient and doctor questionnaires were collected after cycles one and three, respectively. TSE duration was significantly longer when reported by patients compared to doctors for six and seven of ten items after cycles one and three, respectively. Due to the combined effect of doctor underreporting of TSE incidence and duration, the mean percentages of cycle days with TSEs were significantly higher for all ten items when based on patient reports. Day of onset could not be evaluated because of insufficient numbers of complete records.

Conclusions: Self-reporting TSE duration is feasible using a CTCAE-derived questionnaire. As doctors tend to underestimate TSE incidence and duration, patient-reported outcomes should be incorporated into clinical practice, perhaps using eHealth technologies, to harness their potential to better estimate total TSE burden.
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http://dx.doi.org/10.1002/cam4.1687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144000PMC
September 2018

Cardiovascular safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients: a prospective evaluation.

Future Oncol 2018 Feb 10;14(5):443-448. Epub 2018 Jan 10.

Medical Oncology I, Fondazione Del Piemonte Per l'Oncologia, IRCCS Candiolo, Turin, Italy.

Aim: The aim of this study is to evaluate cardiotoxicity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer patients (pts) with cardiovascular comorbidities or coronary artery disease (CAD) risk factors.

Patients & Methods: We prospectively analyzed pts receiving AA in order to evaluate correlations between cardiotoxicity onset and CAD risk factors or cardiovascular comorbidities.

Results: Eighty-seven pts were enrolled, with median treatment duration of 9 months (1-44). At baseline, 84 pts (96%) had CAD risk factors. During treatment four pts (4; 6%) developed hypertension and 26 pts (30%) worsened the preexisting hypertension. Median left ventricular ejection fraction were 64 and 63% at baseline and after treatment, respectively.

Conclusion: AA appears to be safe in pts with cardiovascular comorbidities or CAD risk factors.
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http://dx.doi.org/10.2217/fon-2017-0385DOI Listing
February 2018

Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases.

ESMO Open 2017 9;2(4):e000253. Epub 2017 Oct 9.

Investigative Clinical Oncology (INCO), Candiolo Cancer Institute-FPO, IRCCS, Candiolo, Italy.

Background: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution.

Methods: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment.

Results: Baseline CSF-derived ctDNA analysis revealed and mutations as well as and c amplification. Post-treatment ctDNA analysis showed decreased markers level in plasma, consistent with extra-CNS disease control, while increased in the CSF, confirming poor treatment benefit in the CNS.

Discussion: Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent a useful companion for clinical management of brain metastases.
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http://dx.doi.org/10.1136/esmoopen-2017-000253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640139PMC
October 2017

PARP1 expression drives the synergistic antitumor activity of trabectedin and PARP1 inhibitors in sarcoma preclinical models.

Mol Cancer 2017 04 28;16(1):86. Epub 2017 Apr 28.

Sarcoma Unit, Medical Oncology, Candiolo Cancer Institute - FPO, IRCCS, Candiolo, Torino, Italy.

Background: Enhancing the antitumor activity of the DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin is an isoquinoline alkylating agent with a peculiar mechanism of action. It binds to minor groove of DNA inducing single- and double-strand-breaks. These kinds of damage lead to the activation of PARP1, a first-line enzyme in DNA-damage response pathways. We hypothesized that PARP1 targeting could perpetuate trabectedin-induced DNA damage in tumor cells leading finally to cell death.

Methods: We investigated trabectedin and PARP1 inhibitor synergism in several tumor histotypes both in vitro and in vivo (subcutaneous and orthotopic tumor xenografts in mice). We searched for key determinants of drug synergism by comparative genomic hybridization (aCGH) and gene expression profiling (GEP) and validated their functional role.

Results: Trabectedin activated PARP1 enzyme and the combination with PARP1 inhibitors potentiated DNA damage, cell cycle arrest at G2/M checkpoint and apoptosis, if compared to single agents. Olaparib was the most active PARP1 inhibitor to combine with trabectedin and we confirmed the antitumor and antimetastatic activity of trabectedin/olaparib combination in mice models. However, we observed different degree of trabectedin/olaparib synergism among different cell lines. Namely, in DMR leiomyosarcoma models the combination was significantly more active than single agents, while in SJSA-1 osteosarcoma models no further advantage was obtained if compared to trabectedin alone. aCGH and GEP revealed that key components of DNA-repair pathways were involved in trabectedin/olaparib synergism. In particular, PARP1 expression dictated the degree of the synergism. Indeed, trabectedin/olaparib synergism was increased after PARP1 overexpression and reduced after PARP1 silencing.

Conclusions: PARP1 inhibition potentiated trabectedin activity in a PARP1-dependent manner and PARP1 expression in tumor cells might be a useful predictive biomarker that deserves clinical evaluation.
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http://dx.doi.org/10.1186/s12943-017-0652-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410089PMC
April 2017

Impact of a risk-based follow-up in patients affected by gastrointestinal stromal tumour.

Eur J Cancer 2017 06 24;78:122-132. Epub 2017 Apr 24.

Sarcoma Unit, Division of Medical Oncology Candiolo Cancer Institute - FPO, IRCCS, Strada Provinciale 142, Km 3.95, 10060 Candiolo, TO, Italy; University of Torino, Department of Oncology, Regione Gonzole, 10, 10043 Orbassano, TO, Italy. Electronic address:

Background: Follow-up aims to precociously identify recurrences, metastases or treatment-related adverse events so as to undertake the appropriate therapy. Guidelines admit lack of knowledge on optimal surveillance schedule, but suggest follow-up based on experts' opinion and risk stratification. To identify the impact, if any, of regular follow-up, we interrogated our prospectively collected database whether early detection of recurrences affected both clinical management and, likely, the outcome.

Patients And Methods: We required information to be available on primary surgery and ≥3°years of follow-up for non-recurring patients. We analysed recurrence characteristics (asymptomatic versus symptomatic, low- versus high tumour burden) and computed tomography (CT) scan counts to detect one recurrence. Kaplan-Meier method estimated recurrence-free survival (RFS), post-recurrence progression-free survival (PR-PFS), and disease-specific overall survival (OS). Comparisons used Hazard ratios (HR) with 95% confidence intervals (CIs). Multivariate analyses employed the Cox proportional hazards model. All tests were two-sided.

Results: Between 01/2001 and 12/2012 we found 233 study-eligible patients. Estimated 5- and 10-year RFS were 61.8% and 50.4%, respectively. After a 68-month median follow-up, we observed 94 (40.3%) recurrences [73/94 (77.7%) asymptomatic versus 21/94 (22.3%) symptomatic and 45/94 (47.9%) low- versus 49/94 (52.1%) high tumour burden]. Multivariate analysis revealed that symptomatic and high tumour burden recurrences were highly predictive of both worse PR-PFS (HR:3.19, P < 0.001; HR:2.80, P = 0.003, respectively) and OS (HR:3.65, P < 0.001; HR:2.38, P = 0.026, respectively). Finally, 29 second (primary) cancers were detected during follow-up.

Conclusions: Regular follow-up detects recurrences at an earlier stage and may be associated with a better PR-PFS and OS for these patients. In the absence of randomised trials, these evidences support follow-up effort and cost.
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http://dx.doi.org/10.1016/j.ejca.2017.03.025DOI Listing
June 2017

New and developing chemical pharmacotherapy for treating hormone receptor-positive/HER2-negative breast cancer.

Expert Opin Pharmacother 2016 Nov 27;17(16):2179-2189. Epub 2016 Sep 27.

a Investigative Clinical Oncology (INCO) , Candiolo Cancer Institute-FPO- IRCCS , Turin , Italy.

Introduction: Endocrine therapy is the mainstay of treatment for a substantial proportion of hormone receptor positive (HR+) breast cancer (BC). Indeed, patients with metastatic disease not immediately life threatening may experience long disease control across several lines of endocrine therapy. The major limitation of this therapeutic approach is primary or acquired resistance. A better understanding of endocrine resistance has resulted in newer targeted agents to be added to endocrine therapy. Areas covered: This review highlights new findings in the treatment of HR+/HER2- BC, with a particular focus on new drugs from phase 3 development onwards. Expert opinion: Combining endocrine therapy with agents targeting putative mechanisms of endocrine resistance is a newer treatment paradigm in HR+ BC. Adding a biologically targeted agent to endocrine therapy results in improved response rate, and clinical benefit rate, and prolonged progression-free survival. A clear advantage in overall survival has not yet been reported. Combination therapy allows to delay chemotherapy but increases toxicities and costs, which are critical factors in decision making in the clinical practice. Moreover, identification and validation of biomarkers of response are needed. Ongoing and future trials should elucidate the role of these compounds in the treatment of HR+/HER2- BC.
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http://dx.doi.org/10.1080/14656566.2016.1236914DOI Listing
November 2016

Successful treatment of gemcitabine-induced acute interstitial pneumonia with imatinib mesylate: a case report.

BMC Cancer 2016 10 12;16(1):793. Epub 2016 Oct 12.

Department of Medical Oncology, University of Turin Medical School, Candiolo Cancer Institute, FPO, IRCCS, Str. Prov.le 142 Km 3.95, 10060, Candiolo, Turin, Italy.

Background: Gemcitabine is currently the standard chemotherapy for the adjuvant treatment of pancreatic cancer. This chemotherapeutic agent is generally well-tolerated, myelosuppression and gastrointestinal toxicity being common side effects. Nevertheless, gemcitabine-induced pulmonary toxicity has been rarely reported. Despite its low incidence, the spectrum of pulmonary injury is wide, including potentially fatal conditions. We report a case of acute interstitial pneumonia related to gemcitabine, completely solved with Imatinib Mesylate (IM).

Case Presentation: The patient was a 69-year-old man, who developed a hypoxemic respiratory distress during adjuvant treatment with gemcitabine for stage IIA pancreatic cancer. The nonspecific diffuse alveolar involvement found on computed tomography (CT), together with the negative tests for infectious aetiology and the continuing severe respiratory failure despite a long course of broad-spectrum therapy, suggested gemcitabine-induced acute pneumonia as the most likely diagnosis. Thus, after the failure of steroids and all other conventional therapies, the patient was treated with imatinib mesylate on the basis of its activity in the management of graft-versus-host-induced lung fibrosis. A follow-up CT scan of chest one month later showed complete resolution of pneumonia.

Conclusion: Despite the low frequency of serious pulmonary toxicity, gemcitabine widespread use warns clinicians to consider this life-threatening toxicity. The favourable clinical outcome with IM treatment was remarkable, warranting additional study of IM in the treatment of lung fibrosis.
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http://dx.doi.org/10.1186/s12885-016-2833-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059971PMC
October 2016

Confirmed Activity and Tolerability of Weekly Paclitaxel in the Treatment of Advanced Angiosarcoma.

Sarcoma 2016 25;2016:6862090. Epub 2016 Feb 25.

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Via Mariano Semmola, 80131 Napoli, Italy.

Background. In several prospective and retrospective studies, weekly paclitaxel showed promising activity in patients with angiosarcoma. Patients and Methods. Our study was originally designed as a prospective, phase II multicenter trial for patients younger than 75, with ECOG performance status 0-2, affected by locally advanced or metastatic angiosarcoma. Patients received paclitaxel 80 mg/m(2) intravenously, at days 1, 8, and 15 every 4 weeks, until disease progression or unacceptable toxicity. Primary endpoint was objective response. Results. Eight patients were enrolled but, due to very slow accrual, the trial was prematurely stopped and further 10 patients were retrospectively included in the analysis. Out of 17 evaluable patients, 6 patients obtained an objective response (5 partial, 1 complete), with an objective response rate of 35% (95% confidence interval 17%-59%). Of note, five responses were obtained in pretreated patients. In the paper, details of overall survival, progression-free survival, and tolerability are reported. Conclusions. In this small series of patients with locally advanced or metastatic angiosarcoma, weekly paclitaxel was confirmed to be well tolerated and active even in pretreated patients.
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http://dx.doi.org/10.1155/2016/6862090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785388PMC
March 2016

Prolonged disease stability with trabectedin in a heavily pretreated elderly patient with metastatic leiomyosarcoma of the thigh and renal failure: a case report and review of the literature.

Oncol Res 2013 ;20(10):483-90

Medical Oncology Unit, Institute for Cancer Research and Treatment, Fondazione del Piemonte per l' Oncologia Candiolo, Turin, Italy.

Leiomyosarcoma represents about 24% of all soft tissue sarcomas and can originate from retroperitoneum, uterus, or extremities. Adequate local control may be achieved with surgery and radiotherapy. In the presence of unresectable metastases either doxorubicin- or gemcitabine-based chemotherapy is the standard of treatment. Nevertheless, prognosis remains poor regardless of the selected chemotherapy regimen, and new effective therapeutic agents for patients with advanced leiomyosarcoma are needed. Trabectedin, a promising new DNA-damaging agent with a mechanism of action that is different from that of traditional alkylating agents, is approved in Europe for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents and in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. We present a case of a 76-year-old patient with progressive metastatic lung lesions from a previously resected primary leiomyosarcoma of the thigh and moderate renal failure, who achieved 17 months of disease stability during third-line treatment with trabectedin. Trabectedin was not associated with any cumulative toxicity and was consistently well tolerated for a total of 22 treatment cycles. Current evidence on trabectedin is also presented.
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http://dx.doi.org/10.3727/096504013x13685487925130DOI Listing
December 2013

Gingival metastasis of a radiotherapy-induced breast angiosarcoma: diagnosis and multidisciplinary treatment achieving a prolonged complete remission.

Anticancer Drugs 2012 Nov;23(10):1112-7

Division of Odontostomatology, Ospedale Umberto I Mauriziano, Torino, Italy.

Angiosarcoma is a rare and highly malignant mesenchymal tumor. Similar to other soft tissue sarcomas, it may arise in any organ, although it occurs more frequently within skin structures like the scalp. Angiosarcoma has a characteristic pattern of local and distant relapse involving primary site, regional lymph nodes, and lung. Patients affected by unresectable relapses or metastases have a dismal prognosis with a median overall survival of less than 9 months. We present the case of a 74-year-old woman who previously underwent total mastectomy for a radiotherapy-induced angiosarcoma of the breast. She subsequently developed a rapidly growing gingival tumor lesion that was in fact a unique distant metastasis of her angiosarcoma. In general, surgery is the mainstay of angiosarcoma treatment, and even metastases are aggressively resected whenever feasible. We describe the successful multidisciplinary treatment that avoided a likely mutilating surgery and review the literature regarding primary and metastatic gingival angiosarcoma.
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http://dx.doi.org/10.1097/CAD.0b013e3283579e0dDOI Listing
November 2012