Activity and safety of temozolomide in advanced adrenocortical carcinoma patients

Abstract

Objective Temozolomide has shown a significant anti-proliferative activity on adrenocortical cancer (ACC) cells in vitro. Design On the basis of these results the drug was prescribed as second/third line in advanced metastatic ACC patients in four referral centers in Italy. Methods We retrospectively collected anagraphic, clinical and pathological data of patients with advanced ACC with disease progression to standard chemotherapy plus mitotane who were treated with temozolomide at the dose of 200 mg/m2/die given for 5 consecutive days every 28 days. The primary endpoint was the disease control rate, defined as objective response or disease stabilization after 3 months. Secondary endpoints were overall survival (OS), progression-free survival (PFS) and drug safety. Results Twenty-eight patients have been included in the study. Ten patients (35.8%, 95% CI: 17.8–53.8) obtained a disease control from temozolomide treatment. In particular, 1 patient had a complete response, 5 patients a partial response and 4 patients stable disease. Median PFS was 3.5 months and median OS was 7.2 months. Disease response was more frequently observed in patients with methylation of O6-methylguanine-DNA methyltransferase (MGMT) gene. Temozolomide therapy was well tolerated and most toxicities were limited to grade G1–2 according to WHO criteria. Conclusion Temozolomide was found active in the management of advanced ACC patients. The disease control rate obtained, however, was short-lived and the prognosis of treated patients was poor.

Frequency and outcome of SARS-CoV-2 infection in patients with adrenocortical carcinoma followed at a reference center in Italy

“…Twenty-three of them (46.9%) were on adjuvant mitotane therapy [5]. Among the 43 patients with metastatic disease, 25 (58.1%) were treated with mitotane, 18 (41.8%) were receiving chemotherapy + mitotane as follows: first line EDP (Etoposide, Doxorubicin, Cisplatin) [6] in 8 patients; second/third line therapies with temozolomide [7] in 5 patients (4%) and gemcitabine-capecitabine [8] in 5 patients (5%). Forty-seven patients (51.1%) were resident in Lombardy while the remaining 45 lived in the rest of Italy.Six ACC patients (6.5%) developed COVID-19 symptoms, five of them resident in Lombardy.…”

Cytotoxic Effect of Trabectedin In Human Adrenocortical Carcinoma Cell Lines and Primary Cells

“…DNA alkylation appears to be a critical point for inducing cytotoxicity in the ACC; indeed, cisplatin is a fundamental component of the EDP-M scheme. Furthermore, results obtained both in vitro [9] and in vivo [10] support the antineoplastic activity of another alkylating agent such as temozolomide against ACC. Trabectedin (ET-743) is a powerful anti-tumor drug isolated from the Caribbean tunicate Ecteinascidia turbinata.…”

Case Report: Exceptional Response to Second Line Temozolomide Therapy in a Patient With Metastatic Adrenocortical Carcinoma

“…In a recently conducted retrospective study, single agent temozolomide was found active as second line approach in advanced ACC patients with a response rate observed in 20% of patients. The disease control rate obtained, however, was short-lived (10).…”