Treatment of refractory adrenocortical carcinoma with thalidomide: results of a retrospective analysis of 15 patients

Objective: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy with a dismal prognosis. The adrenotoxic drug mitotane and cytotoxic chemotherapy are considered standard of care in advanced stages but tumor control is often short-lived. Due to its anti-angiogenic properties, the use of thalidomide may be promising in this context.

Methods: We performed a retrospective analysis from the German Adrenocortical Carcinoma Registry, evaluating the outcome of patients with refractory ACC treated with thalidomide. Main outcome measures were best response during treatment, progression-free survival (PFS), and overall survival (OS).

Results: Fifteen patients (7 males; median age 48.9 years) with refractory ACC progressing after mitotane and up to six systemic treatments were enrolled. Thalidomide was administered according to tolerability (median starting dose 100 mg/d, maximum dose 400 mg/d), and follow-up was usually performed every 12 ± 3 weeks (median interval between treatment initiation and first staging 10.9 weeks, range 4.4 to 19.3 weeks). The best response to treatment was stable disease (n = 2) and progressive disease (n = 13), with a median PFS of 10.9 weeks (range 4.4 to 34.4 weeks) and a median OS of 34.4 weeks (range 5.1 to 111.1 weeks). With respect to the two patients with stable disease, the first discontinued treatment due to epistaxis and diarrhea. The other had ongoing stable disease according to RECIST criteria for more than 6 months. However, the dose of thalidomide was low and the overall course of the disease had been relatively slow before. Moderate gastrointestinal disorders and unspecific general symptoms were the most common adverse events and usually of mild nature.

Conclusion: Thalidomide was overall well tolerated but did not result in clinically meaningful disease stabilization in the majority of patients in this heavily pretreated cohort.