Mitotane 500mg tablets

ContextAdrenocortical carcinoma (ACC) is a rare, aggressive malignancy with a high recurrence and mortality rate even after complete resection. Therefore, intensification of adjuvant therapies is crucial, although their effectiveness remains controversial.ObjectiveThis study aimed to determine the efficacy and safety of available treatments by considering the prognostic factors affecting disease outcomes.MethodsThe search was conducted across 3 databases (PubMed, Embase, and CENTRAL) in October 2024. Eligible studies compared overall survival (OS) and recurrence-free survival (RFS) in patients with ACC treated with and without systemic (mitotane, cytotoxic chemotherapy) or localized (radiotherapy) nonsurgical treatments. In total, 86 studies met the inclusion criteria for the systematic review, and 62 for the meta-analysis. Two reviewers extracted data independently. Adjusted hazard ratios (aHR) with 95% CI were calculated for survival outcomes.ResultsMitotane significantly improves OS (aHR: 0.54; CI: 0.41-0.70) and RFS (aHR: 0.60; CI: 0.43-0.84), even in stage I-III disease (OS aHR: 0.71; CI: 0.52-0.98; RFS aHR: 0.65; CI: 0.50-0.85). Radiotherapy showed a trend toward improved OS (aHR: 0.66; CI: 0.38-1.15) and RFS (aHR: 0.65; CI: 0.35-1.23), with significant benefits in stage I-III (OS aHR: 0.68; CI: 0.50-0.93; RFS aHR: 0.71; CI: 0.63-0.81). The impact of cytotoxic chemotherapy on OS remains uncertain (aHR: 0.61; CI: 0.08-4.78).ConclusionMitotane significantly improves survival outcomes in patients with ACC, while radiotherapy exhibits potential benefits, particularly in localized disease. Further research is needed to verify the efficacy of cytotoxic chemotherapy, and randomized controlled trials are required to provide robust evidence of different treatment approaches.

Abstract licence: CC BY

Background: Advanced adrenocortical carcinoma (ACC) remains a challenging malignancy with limited therapeutic options. Multi-kinase inhibitors (MKIs), either alone or in combination with immuno-oncology (IO) agents, have been investigated in recent single-arm clinical trials and retrospective series. Methods: We conducted a systematic review and single-arm meta-analysis of studies evaluating MKIs in advanced ACC. Objective response rate (ORR) and disease control rate (DCR) were pooled using random-effects models for single-arm proportions. Overall survival (OS) and progression-free survival (PFS) were summarized descriptively due to limited variance data. Subgroup analyses compared MKI monotherapy versus MKI + IO combinations, and meta-regression was performed to assess the impact of prior mitotane exposure. Results: Eleven studies (n = 208 patients) were included. The pooled ORR was 21% (95%CI, 11-36%), and the DCR was approximately 57%. Subgroup analysis revealed a higher ORR with MKI + IO regimens (26%; 95%CI, 12-48%) compared to MKI monotherapy (15%; 95%CI, 3-47%). Median OS ranged from 5.4 to 30.6 months, and PFS from 2.8 to 13.3 months, both favouring MKI + IO combinations. Meta-regression identified prior mitotane exposure as a significant predictor of ORR (p = 0.0279), particularly within the MKI + IO subgroup. Conclusions: MKI-based regimens, especially when combined with IO, demonstrate promising efficacy in advanced ACC, a disease with few established second-line options. While limited by the non-comparative design of available studies, these findings support further investigation in prospective, randomized clinical trials.

Abstract licence: CC BY