Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial

Berruti, Alfredo; Terzolo, Massimo; Sperone, Paola; Pia, Anna; Casa, Silvia Della; Gross, David J.; Carnaghi, Carlo; Casali, Paolo G.; Porpiglia, Francesco; Mantero, Franco; Reimondo, Giuseppe; Angeli, Alberto; Dogliotti, Luigi

doi:10.1677/erc.1.01025

Cited by 272 publications

(229 citation statements)

References 28 publications

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“…An international network of closely collaborating investigators was the key to achieving this enrollment of patients within only 5.4 years, which is equivalent to a recruitment rate of 56 patients per year, as compared with a maximum of 7 patients per year in previous studies. 17,[25][26][27][28] This successful enrollment shows that an investigator-initiated, randomized phase 3 trial of treatment in patients with a rare tumor is feasible, despite the lack of pharmaceutical interest in sponsoring such a trial. Further strengths of the trial include its prospective, randomized design; the intentionto-treat analysis; the high percentage of patients who were evaluated for the predefined end points; and the small number of censored observations.…”

Section: Discussionmentioning

confidence: 99%

Combination Chemotherapy in Advanced Adrenocortical Carcinoma

Fassnacht¹,

Terzolo²,

Allolio³

et al. 2012

N Engl J Med

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738

502

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Section: Discussionmentioning

confidence: 99%

Combination Chemotherapy in Advanced Adrenocortical Carcinoma

Fassnacht¹,

Terzolo²,

Allolio³

et al. 2012

N Engl J Med

Self Cite

738

502

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“…Leukopenia is one of the dose-limiting side effects of the classical Berruti (EDP-M) protocol (Berruti et al 2005) and further commonly observed serious adverse effects associated with doxorubicin or cisplatin include cardiotoxicity and nephrotoxicity (Fassnacht et al 2012). Liposomal encapsulation of cisplatin (Boulikas 2004, Devarajan et al 2004) and doxorubicin (Harrington et al 2002, Huwyler et al 2008 has been shown to quench these drug-specific side effects.…”

Section: Discussionmentioning

confidence: 99%

Liposomal polychemotherapy improves adrenocortical carcinoma treatment in a preclinical rodent model

Hantel¹,

Jung²,

Mussack³

et al. 2014

Endocrine-Related Cancer

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Owing to high relapse rates and early metastatic spread, prognosis in adrenocortical carcinoma (ACC) patients remains poor, highlighting the importance of developing new treatment alternatives for them. Recently, polychemotherapy regimens including etoposide, doxorubicin, and cisplatin together with mitotane (EDP-M) have been defined as the standard treatment for late-stage disease patients. Nevertheless, the administration of conventional cytostatic drugs is associated with severe and dose-limiting side effects. In an attempt to optimize existing clinical treatment regimens, in this study, we investigated the therapeutic efficacy of EDP-M in comparison with that of a paclitaxel-modified scheme (paclitaxel, doxorubicin, cisplatin plus mitotane (PDP-M)) in preclinical in vitro and in vivo models. In addition, based on an extraordinary uptake phenomenon of liposomes in ACC cells, we further evaluated liposomal variants of these protocols (etoposide, liposomal doxorubicin, liposomal cisplatin plus mitotane (LEDP-M) and nab-paclitaxel, liposomal doxorubicin, liposomal cisplatin plus mitotane (LPDP-M)). In vitro, PDP-M was more potent in the induction of apoptosis and inhibition of cell viability as well as cell proliferation than EDP-M. Following the administration of a single therapeutic cycle, we further demonstrated that LEDP-M and LPDP-M exerted significant antitumoral effects in vivo, which were not as evident upon EDP-M and PDP-M treatments. These results were confirmed in a long-term experiment, in which the highest and sustained antitumoral effects were observed for LEDP-M. In summary, liposomal cytostatic substances could represent a promising option that deserves testing in appropriate clinical protocols for the treatment of ACC patients.

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“…Surgery is regarded as therapy of choice in all patients with resectable tumour, but 25% of patients already have distant metastases at the time of primary diagnosis and the majority of patients develop metastases even after assumed curative surgery (2-12). In 2003, an international consensus conference on the management of ACC recommended for patients with advanced metastatic disease mitotane as monotherapy or combined with etoposide, doxorubicin and cisplatin (13) or with streptozotocin (14) as first-line systemic treatment based on two phase II trials leading to an evidence level not better than 2 (1). The two latter regimens are currently compared in the first randomized trial in this disease (FIRM-ACT trial, www.firm-act.org).…”

Section: Introductionmentioning

confidence: 99%