Adrenocortical cancer or cancer of the adrenal glands (glands located just above the kidneys) is a rare type of cancer with low chances of survival. Data on the usefulness of chemotherapy for this cancer is limited. Hence, the First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma Treatment (FIRM-ACT) was planned, which compared two chemotherapy regimens in advanced adrenocortical cancer. The first regimen included etoposide, doxorubicin, and cisplatin (EDP) with mitotane for 4-week cycles, while the second regimen included streptozocin with mitotane for 3-week cycles. Patients who showed disease progression with a particular regimen were switched over to the alternative regimen as a second-line treatment.
The study was conducted in 40 specialized centers across 12 countries between June 2004 and October 2009. A total of 304 patients participated in the study.
AdvertisementA positive response to treatment was seen in 23.2% patients in the EDP-mitotane group, which was significantly higher than the number of patients responding to the streptozocin-mitotane regimen i.e. 9.2% patients. In fact, three patients in the EDP-mitotane group showed a complete response to treatment, and 6 patients showed a partial response. These 6 patients later underwent surgery, which made them free of the cancer.
The median duration of progression-free survival was double in the EDP-mitotane group (5 months) as compared to the streptozocin-mitotane group (2.1 months).
However, first-line therapy with EDP-mitotane did not result in a significant improvement in overall survival, as compared with streptozocin-mitotane regimen (14.8 months vs. 12.0 months).
Adverse effects including serious ones were more common with the EDP-mitotane regimen when used as first-line treatment, as compared to the streptozocin-mitotane regimen, though the difference was not statistically significant.
The study thus concludes that a chemotherapy regimen consisting of etoposide, doxorubicin and cisplatin (EDP-mitotane) has better effect on adrenocortical cancer as compared to the streptozocin-mitotane regimen, with a similar incidence of side effects. However, the regimen failed to produce a significant improvement in overall survival; hence newer therapies should be investigated to improve the prognosis of patients suffering from adrenocortical cancer.
Combination Chemotherapy in Advanced Adrenocortical Carcinoma; Martin Fassnacht et al; N Engl J Med 2012; 366:2189-2197