Publications by authors named "Marco Gizzi"

9 Publications

  • Page 1 of 1

Rhabdomyolysis and acute kidney injury induced by the association of rosuvastatin and abiraterone: A case report and review of the literature.

J Oncol Pharm Pract 2021 Jan 12;27(1):216-219. Epub 2020 May 12.

Department of Intensive Care, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

Introduction: Abiraterone acetate is an inhibitor of androgens biosynthesis, approved as first-line treatment in castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer. Abiraterone has been rarely associated with severe rhabdomyolysis, but the mechanism of muscle toxicity is unknown.

Case Report: We hereby present a case of severe rhabdomyolysis resulting in acute on chronic kidney injury following abiraterone initiation in a patient previously under rosuvastatin.

Management And Outcome: Rhabdomyolysis was resolutive after rosuvastatin and abiraterone discontinuation, and kidney function recovered. There was no recurrence of muscle toxicity after re-initiation of abiraterone alone.

Discussion: Abiraterone selectively inhibits CYP17 as well as the hepatic transporter OATP1B1. OATP1B1 is an efflux transporter, whose function is to extract several drugs from the portal blood, allowing them to undergo hepatic metabolism. We hypothesize that abiraterone-induced inhibition of plasmatic uptake of rosuvastatin by OATP1B1 increased plasmatic concentration of rosuvastatin, leading to toxicity on muscle cells. We therefore suggest that the association between rosuvastatin and abiraterone should be avoided.
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http://dx.doi.org/10.1177/1078155220923001DOI Listing
January 2021

Efficacy and Tolerability of Tremelimumab in Locally Advanced or Metastatic Urothelial Carcinoma Patients Who Have Failed First-Line Platinum-Based Chemotherapy.

Clin Cancer Res 2020 01 4;26(1):61-70. Epub 2019 Dec 4.

St-Augustinus Ziekenhuis, Antwerp, Belgium.

Purpose: Patients with advanced urothelial carcinoma who fail platinum-containing chemotherapy (treatment fails) have a poor prognosis and limited treatment options. Recent approvals of immune-checkpoint inhibitors confirmed the value of immunomodulatory therapy in urothelial carcinoma. Tremelimumab is a selective human immunoglobulin G2 (IgG2) monoclonal antibody against cytotoxic T-lymphocyte-associated antigen 4 with demonstrated durable response rate in metastatic melanoma. This is the first study to report the efficacy and safety of tremelimumab in urothelial carcinoma.

Patients And Methods: We report the results of the urothelial carcinoma cohort from a phase II, open-label, multicenter study of patients with advanced solid tumors (NCT02527434). Patients with locally advanced/metastatic urothelial carcinoma were treated with tremelimumab monotherapy (750 mg via intravenous infusion every 4 weeks for seven cycles, then every 12 weeks for two additional cycles) for up to 12 months or until disease progression, initiation of other anticancer therapy, unacceptable toxicity, or consent withdrawal.

Results: In 32 evaluable patients with metastatic urothelial carcinoma, objective response rate was 18.8% (95% confidence interval, 7.2-36.4), including complete response (CR) in 2 (6.3%), and partial response in 4 patients (12.5%). Median duration of response has not been reached. Stable disease of ≥12 months was reported in 1 patient (3.1%), yielding a disease control rate at 12 months of 21.9%. Overall, tremelimumab was generally well tolerated; safety results were consistent with the known safety profile.

Conclusions: Tremelimumab monotherapy demonstrated clinical activity and durable responses in patients with metastatic urothelial carcinoma. This study is the first in which CR has been observed with tremelimumab as a single agent in urothelial carcinoma.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1635DOI Listing
January 2020

Advancing therapies in metastatic castration-resistant prostate cancer.

Expert Opin Pharmacother 2018 11 12;19(16):1797-1804. Epub 2018 Oct 12.

a Department of Medical Oncology , Institut Gustave Roussy, University of Paris Sud , Villejuif , France.

Introduction: Prostate cancer is the second most common cause of cancer worldwide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the cornerstone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatments have dramatically improved overall survival of men with mCRPC. Current therapies are based on AR-axis inhibitors and taxane-based chemotherapies, as well as radiopharmaceuticals and Sipuleucel T.

Areas Covered: The authors provide a review of the current field of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies.

Expert Opinion: Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, as well as in non-metastatic castration-resistant patients, it is expected that a growing subgroup of patients will be exposed earlier to chemotherapy and to AR targeted agents. It becomes then fundamental to find novel strategies to overcome drug resistance and further improve survival.
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http://dx.doi.org/10.1080/14656566.2018.1527312DOI Listing
November 2018

[Atezolizumab (Tecentriq): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma].

Bull Cancer 2018 Feb 28;105(2):140-145. Epub 2017 Dec 28.

University of Paris Sud, Gustave Roussy cancer campus, drug development department, 94805 Villejuif cedex, France; University of Paris Sud, Gustave Roussy cancer campus, department of medical oncology, 94805 Villejuif cedex, France. Electronic address:

Treatments for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin are currently limited. Atezolizumab (Tecentriq) is a monoclonal antibody targeting PD-L1. The first of IMVIGOR 210 phase II trial (NCT02951767) investigated atezolizumab as front line treatment among 119 patients with metastatic urothelial cancer unfit for cisplatin. Response rate was 23% and median overall survival 15.9 months. The second cohort (NCT02108652) included 310 patients whose tumors were progressing after first line platinum-based chemotherapy. Response rate was 15% and median overall survival 7.9 months. Among patients with high PD-L1 expression on infiltrating immune cells (ICs), response rate was 26% and median overall survival 11 months. Atezolizumab was well-tolerated in both cohorts with 66% of treatment-related toxicities including 12% (cohort 1) and 7% (cohort 2) of grade 3-4 adverse events. These results led to an approval by the FDA in United States and the EMA in Europe. In France, atezolizumab was available through an early access agreement by the French National Agency for Medicines and Health Products (ANSM) for patients with metastatic or advanced urothelial carcinomas on progression after first line chemotherapy or unfit for cisplatin. So far, its avaibility in France within the EMA approval is pending its pricing.
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http://dx.doi.org/10.1016/j.bulcan.2017.10.030DOI Listing
February 2018

Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours.

Eur J Cancer 2016 12 4;69:151-157. Epub 2016 Nov 4.

Department of Cancer Medicine, Institut Gustave Roussy, Université Paris-Sud, 94800 Villejuif, France. Electronic address:

Background: Patients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE. The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT).

Methods: Between 2001 and 2014, 295 patients received first-line cisplatin-based chemotherapy for GCT. Preventive anticoagulation with low-molecular-weight heparin (LMWH) was progressively implemented in patients with predictive factors. Sixteen patients with evidence of TEE before starting chemotherapy were excluded from the analysis.

Results: Among 279 eligible patients, a TEE occurred in 38 (14%) consisting of DVT (n = 26), arterial thrombosis (n = 2), and superficial thrombophlebitis (n = 10). DVT occurred in 26 (12.7%) of 204 patients with risk factors versus two (2.6%) of 75 patients with no risk factors (p = 0.01). After a prevention protocol was progressively implemented from 2005, primary thromboprophylaxis was administered to 104 patients (68%) with risk factors. Among patients at risk (n = 151), the incidence of DVT decreased by roughly half when they received a LMWH: 9/97 (9.2%) and 9/54 (16.6%), respectively (p = 0.23).

Conclusion: Patients with GCT who receive cisplatin-based chemotherapy are at risk of developing a TEE which can be predicted by elevated serum LDH. To our knowledge this is the first study exploring LMWH as thromboprophylaxis in GCT patients. A prospective trial testing prophylactic anticoagulation is warranted.
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http://dx.doi.org/10.1016/j.ejca.2016.10.003DOI Listing
December 2016

Late recurrent testicular seminoma: histological evidence is required.

Oncol Res Treat 2015 19;38(6):286-8. Epub 2015 May 19.

Department of Cancer Medicine, Gustave-Roussy Cancer Campus, Villejuif, France.

Introduction: Over the past 3 decades, the appropriate management of metastatic germ cell tumours (GCT) has been defined by several phase III trials. Many follow-up recommendations have been published based on expert consensus. However, common clinical scenarios can still be vexing for clinicians who are less experienced at managing patients with testicular cancer.

Case Report: We highlight the arduous diagnostic work-up of a suspected late relapsing metastatic GCT in a patient suffering from fatigue, weight loss and prominent retroperitoneal lymph nodes, 4 years after first-line chemotherapy for metastatic seminoma. The various explorations finally led to the diagnosis of Whipple's disease.

Conclusion: This unusual clinical case strongly highlights the need to perform an exhaustive evaluation, with a biopsy, if a late recurrent GCT is suspected to avoid pointless and potentially harmful treatment.
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http://dx.doi.org/10.1159/000430794DOI Listing
March 2016

Axitinib in metastatic renal cell carcinoma.

Expert Rev Anticancer Ther 2015 May;15(5):499-507

Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.

Axitinib is the most recent targeted therapy approved by the US FDA and EMA in the treatment of metastatic renal cell carcinoma (mRCC). It is a second-generation, orally available, potent tyrosine kinase inhibitor targeting selectively VEGF receptor (VEGFR)-1, -2 and -3, resulting in inhibition of angiogenesis, metastasis and tumor growth. Based on the results of a randomized pivotal Phase III clinical trial, axitinib stands as one of the two recommended agents for patients with mRCC who progressed after first-line tyrosine kinase inhibitor therapy. Its potent and selective inhibition of VEGFR was the rationale for its development in the second-line setting after failure of prior cytokines or sunitinib. Here we examine the preclinical and clinical data of axitinib for mRCC, and its use in the treatment algorithm.
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http://dx.doi.org/10.1586/14737140.2015.1033408DOI Listing
May 2015

Tubulocystic carcinoma of the kidney with fatal outcome in an adolescent male.

Urol Int 2015 16;94(4):485-7. Epub 2014 Dec 16.

Service d'oncologie médicale, Cliniques universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium.

Non-clear cell renal cell carcinoma accounts for about 20% of all kidney cancers. Tubulocystic carcinoma of the kidney (TCK) is a newly described entity with distinct molecular, genetic and clinical features. In 2013, it was one of five new renal tumors to be recognized by the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia. We describe here a case of TCK with a rare genetic signature, unusual metastases and limited response to an anti-vascular endothelial growth factor inhibitor in what we believe is the youngest patient on record to date.
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http://dx.doi.org/10.1159/000366287DOI Listing
March 2016