Abstract
Etoposide, doxorubicin and cisplatin plus oral mitotane (EDP-M) comprise the reference regimen in the management of patients with adrenocortical carcinoma (ACC). In this paper, we described the outcome of 58 patients with advanced/metastatic ACC consecutively treated with EDP-M in a reference center for this rare disease in Italy. In this series, EDP-M obtained a partial response in 50% of patients; median progression free survival (PFS) and overall survival were 10.1 months (95% Confidence Interval [CI 95%] 8.1–12.8) and 18.7 months (95% CI: 14.6–22.8), respectively. EDP-M was not interrupted in five patients showing disease progression after two cycles without the appearance of new lesions and mitotane levels below the therapeutic range. In two of them, the disease remained stable at further imaging evaluations and the other three obtained a partial response. Twenty-six responding patients underwent surgery of residual disease and 13 of them became disease free. Surgery identified a pathological complete response (pCR) in four patients (7%) and Ki67 expression in post-chemotherapy tumor specimens, inferior to 15% (median value), was associated with better PFS and survival. In the present study, the EDP-M regimen is confirmed to have a limited efficacy. Early disease progression does not mean treatment inefficacy. Surgery of residual disease in partially responding patients allows for the detection of pCR in few of them and this condition is predictive of long-term survival. Ki67 expression of post-chemotherapy residual disease could be an additional prognostic factor that deserves to be studied further.
Highlights
Adrenocortical carcinoma (ACC) is a rare tumor with an estimated incidence in Western countries of 0.7–2 new cases per million population per year [1].Surgery is the mainstay of therapy and represents the only treatment modality able to offer a chance of a cure
We present the outcome of a consecutive series of patients with advanced/metastatic adrenocortical carcinoma (ACC) treated with EDP-M at a tertiary referral oncology center in Italy
In this series of advanced/metastatic ACC patients, uniformly treated in a reference oncology center for this rare disease in Italy, the EDP-M regimen was confirmed to be active. Both the overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (50%) and the progression free survival (PFS) observed in this study were higher than the ones reported with EDP-M in the FIRM-ACT trial and were similar to those observed in the Italian phase 2 trial [9,10]
Summary
Adrenocortical carcinoma (ACC) is a rare tumor with an estimated incidence in Western countries of 0.7–2 new cases per million population per year [1].Surgery is the mainstay of therapy and represents the only treatment modality able to offer a chance of a cure. Mitotane has been the reference drug for ACC This compound is efficacious when serum levels reach the so-called therapeutic range (14–20 mg/L) [3], which is not usually attained before 2–3 months of therapy. An EDP-M scheme was first introduced in 1992, when it was found to be active in the management of two young ACC patients, both obtaining a partial response lasting 7 and 21 months, respectively [6]. The feasibility of this regimen was subsequently assessed on 7 consecutive patients [7], a formal prospective phase II trial was designed and conducted in Italy. The median progression free survival (PFS) and overall survival (OS) of the entire cohort were 9.1 and 28.5 months, respectively [9]
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