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.
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
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
Combination Chemotherapy in Advanced
Adrenocortical Carcinoma; Martin Fassnacht et al; N Engl J Med 2012;