# FIRM-ACT: combination chemotherapy in advanced adrenocortical carcinoma

Source: https://onco.cc/key-papers/paper-firm-act-edp-mitotane-adrenocortical-carcinoma-nejm-2012/  
OnCo record `paper-firm-act-edp-mitotane-adrenocortical-carcinoma-nejm-2012` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first randomised trial in advanced adrenocortical carcinoma showed that etoposide, doxorubicin and cisplatin with mitotane shrank tumours more often and held them back longer than streptozocin with mitotane, making EDP-mitotane the standard.

## Summary

International randomised phase 3 trial of 304 patients with advanced adrenocortical carcinoma assigned to etoposide, doxorubicin and cisplatin plus mitotane (EDP-M) or streptozocin plus mitotane, with crossover at progression.

Response rates were 23.2 percent with EDP-M against 9.2 percent, and median progression-free survival 5.0 against 2.1 months; median overall survival was 14.8 against 12.0 months, not statistically different, partly because of crossover. Serious adverse events were similar.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: New England Journal of Medicine
- Year: 2012
- DOI: 10.1056/NEJMoa1200966
- Authors: Fassnacht M, Terzolo M, Allolio B, et al.
- Findings: Response rate 23.2 percent with EDP-mitotane versus 9.2 percent with streptozocin-mitotane.; Median progression-free survival 5.0 versus 2.1 months; overall survival 14.8 versus 12.0 months (not significant).
- What it means: EDP-mitotane is the first-line chemotherapy for adrenocortical carcinoma that cannot be removed, and the comparator arm for new trials; outcomes remain poor and better drugs are needed.
- Caveats: Overall survival did not differ significantly; crossover diluted the comparison.; Toxicity of EDP-M is substantial in a population often already unwell from cortisol excess.

## Sources

- N Engl J Med 2012: https://doi.org/10.1056/NEJMoa1200966
- PubMed: https://pubmed.ncbi.nlm.nih.gov/22551107/

## Connected records

- cancers: [Advanced and metastatic adrenocortical carcinoma (ENSAT stage IV or unresectable)](https://onco.cc/cancers/advanced-adrenocortical-carcinoma/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Mitotane](https://onco.cc/drugs/mitotane/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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