Efficiency of chemotherapy GemCap + mitotane as second and subsequent lines of therapy for metastatic adrenocortical cancer

Background. Combination of gemcitabine, metronomic capecitabine and mitotane (GemCap + m) is the most studied regimen in second and subsequent lines of therapy for advanced adrenocortical cancer (ACC). Previously published studies do not give a definitive answer to the question- what plays a key role in realizing the response to treatment: chemotherapy or mitotane in therapeutic concentration.

Aim. Evaluation the efficacy and safety of GemCap + m combination with the standard dosing regimen of capecitabine in patients with metastatic ACC.

Materials and methods. This retrospective single-center clinical study included patients over 18 years of age with histologically confirmed ACC with disease progression after completion of platinum-containing therapy. They received chemotherapy regimen gemcitabine 800 mg/m² for days 1, 8 and capecitabine 1000 mg/m² orally 2 times at days 1–14 of the 21-day cycle with mitotane. we evaluated objective response, stabilization of disease, 6-months disease control rate and median progression-free and overall survival. Radiological assessment according to RECIST 1.1 criteria was carried out every 6–8 weeks of treatment.

Results. The study included 25 patients. mitotane concentration above 14 ng/mL was achieved in 22 (88 %) patients, of which 21 (84 %) reached therapeutic concentration in previous treatment lines. 80 % of patients received treatment as 2^nd line, 20 % as 3^rd and subsequent lines. The objective responses and disease stabilization was observed in 1 (4 %) and 11 (44 %) of patients, respectively. Disease control for at least 6 months rate was 24 %. median progression-free and overall survival were 3.2 months and 12.17 months, respectively. Toxicity grade 3–4 was observed in 28 % of patients. gemcitabine dose reductions due to thrombocytopenia grade 1–2 were required in 2 cases (8 %), no capecitabine reductions were necessary.

Conclusion. This study demonstrates the effectiveness of a new dose regimen of chemotherapy GemCap + m in the second and subsequent lines of therapy for metastatic ACC. The progression of the disease against the background of previous lines of therapy at a therapeutic concentration of mitotane in the majority of patients indicates the effectiveness of the chemotherapeutic component of gemCap in a cohort of patients resistant to platinum and mitotane.