聯合免疫療法Nivolumab和Ipilimumab在轉移性腎上腺皮質癌的治療-案例報告

陳建凱、陳柏華、石宏仁、江恒杰

彰化基督教醫院泌尿外科

Nivolumab and Ipilimumab Combination Therapy in Metastasis Adrenocortical Carcinoma Patient: A Case Report

Jian-Kai Chen, Pao-Hwa Chen, Hung-Jen Shih, Heng-Chieh Chiang

Division of Urology, Department of Surgery, Changhua Christian Hospital

The preferred regimens of systemic treatment to the metastasis adrenocortical carcinoma are EDP (etoposide, doxorubicin, and cisplatin) plus mitotane. The other choice of treatment are monotherapy of mitotane and the immunotherapy. Here, we present a 70-year-old woman with metastatic adrenocortical carcinoma that progressed after adjuvant mitotane and single immunotherapy. The treatment of Nivolumab and Ipilimumab achieved partial response after 3 months.

A 70-year-old lady without any previous medical history was diagnosed with supra-renal mass during routine hematuria work-up at the urology department. The biochemical workup showed no evidence of adrenal cortical dysfunction or pheochromocytoma. A 4-cm heterogenous enhanced oval mass at left adrenal gland was noted in abdomen CT. The retroperitoneoscopic left adrenalectomy was done. Due to adverse pathology, we recommended local radiotherapy with systemic mitotane use as adjuvant treatment after surgery. During the follow-up CT scan, multiple small nodular lesions in left perirectal space and posterior pararenal space were found. CT guide biopsy was arranged to determine the pathology of the mass, which revealed to be adrenal corticocarcinoma. After discussing with the patient, we decided on retroperitoneal debulking which included left retroperitoneal mass and soft tissue removal with nephrectomy and splenectomy. Final pathology does not show spleen or kidney involvement. Three months later, PET CT showed diffused peritoneal and right retroperitoneal seeding. A mass on right subphrenic area between diaphragm and liver. Thoracic surgeon used VATS to remove the mass in minimal invasive manner.  A second debulking operation was done to remove the peritoneal and retroperitoneal seeding. Since the patient refuse chemotherapy, we suggest single immunotherapy with Pembrolizumab as adjuvant therapy after operation. After 5 courses of Pembrolizumab, the PET scan still showed progressive disease. Chemotherapy was then discussed, but patient wish to try other immunotherapy. Three courses of Atezolizumab was then attempted but subsequent PET scan still showed poor response with increased uptake in the right subphrenic region. After researching for other options, a clinical phase II trial with Nivolumab and Ipilimumab is currently under examination; therefore we suggest combination therapy to the patient. We followed the recommended phase II trial dosing for the initial 3 months. During the initial treatment period, patient started to have high blood glucose level, hypertension and hypokalemia episodes. Endocrinologist and nephrologist was then consulted to control her underlying side effects. After initial 3 months period, the follow-up PET CT showed partial response with decrease FDG hypermetabolism in the liver at S4, S6, the abdomen including omentum region and retroperitoneum, and in the right peri-rectal region. Patient was able to finished the initial dosing of Nivolumab and Ipilimumab. Unfortunately, patient had a case of sudden cardiac arrest at home when awaiting for maintenance Nivolumab dosing.