Abstract
Background
Adrenocortical carcinoma (ACC) is a rare tumor with an incidence of one per million population per year. Overall prognosis is poor especially in the presence of distant metastasis where five-year survival rate is 10%. Aside from chemotherapy along with mitotane, second-line regimens are not well-established, and therapeutic options remain limited. Here we present a case of metastatic ACC with rapid and complete remission after salvage therapy with gemcitabine (GEM).
Clinical Case
A 28-year-old man presented with night sweats, 10-lb weight loss and abdominal pain for three months. An abdominal CT showed a 13x14 cm complex mass partially effacing the inferior vena cava (IVC) and a chest CT showed multiple pulmonary micronodules. Biochemical evaluation was unremarkable, confirming a non-functioning adrenal tumor.
The patient underwent right adrenalectomy, hepatectomy, right diaphragm resection and cavotomy of IVC. Pathology confirmed ACC with extra-adrenal and vascular invasion. He then underwent adjuvant intensity-modulated radiation therapy with no evidence of disease on imaging thereafter. However, he was lost to follow-up for six months and returned with new enlarging pulmonary nodules.
He was started on chemotherapy (cisplatin, etoposide, adriamycin) with mitotane which were discontinued after two months, due to intractable vomiting despite high dose glucocorticoids and anti-emetics. He was then enrolled in a clinical trial using immunotherapy with nivolumab and ipilimumab which led to a significant decrease in the size of pulmonary metastases. His clinical course was complicated by the development of type 1 diabetes mellitus and proliferative glomerulonephritis related to immunotherapy.
After one year of immunotherapy, repeat imaging showed disease progression with new pulmonary nodules. These agents were discontinued, and he was then given a single dose of GEM. Subsequent imaging with CT chest, abdomen and pelvis three months later showed complete response with resolution of lung nodules. He has no evidence of disease one year post therapy and continues to undergo active surveillance.
Discussion
GEM-based chemotherapy has shown to be a modestly active regimen based on a multicenter study which demonstrated a partial response or stable disease in 4.9% and 25% of cases, respectively, with a median duration of 26 weeks. Median progression-free survival is 12 weeks (range 1 to 94). From the available data, GEM remains an important option for salvage therapy however, to date, there are no reliable predictive biomarkers to potentially identify responsive patients.
Conclusion
This is an extremely rare case of metastatic ACC achieving complete response after definitive surgery and a single dose of gemcitabine, despite failing first-line chemotherapy and immunotherapy. The unusual positive response may lead to the consideration of its use as a second line regimen.
Advanced Adrenocortical Carcinoma (ACC): a Review with Focus on Second-Line Therapies
