Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy.
Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Endocrine. 2022 Sep;77(3):438-443. doi: 10.1007/s12020-022-03075-y. Epub 2022 May 14.
The management of patients with advanced/metastatic adrenocortical carcinoma (ACC) is challenging, EDP-M (etoposide, doxorubicin, cisplatin combined with mitotane) is the standard regimen. However, it is quite toxic, so an adequate supportive therapy is crucial to reduce as much as possible the side effects and maintain the dose intensity of cytotoxic agents.
We describe the main side effects of the EDP-M scheme and the best way to manage them based on the experience of the Medical Oncology Unit of the Spedali Civili of Brescia. We also deal with the administration of EDP-M in specific frail patients, such as those with huge disease extent and poor performance status (PS) and those with mild renal insufficiency.
In patients with hormone secreting ACC the rapid control of Cushing syndrome using adrenal steroidogenesis inhibitors such as metyrapone or osilodrostat is mandatory before starting EDP-M. Primary prophylaxis of neutropenia with Granulocyte-Colony Stimulating Factors is crucial and should be introduced at the first chemotherapy cycle. Possible mitotane induced hypoadrenalism should be always considered in case of persistent nausea and vomiting and asthenia in the interval between one cycle to another. In case of poor PS. A 24 h continuous infusion schedule of cisplatin could be an initial option in patients with poor PS as well as to reduce the risk of nefrotoxocity in patients with mild renal impairment.
A careful and accurate supportive care is essential to mitigate EDP-M side effects as much as possible and avoid that, due to toxicity, patients have to reduce doses and or postpone cytotoxic treatment with a negative impact on efficacy of this chemotherapy regimen.
晚期/转移性肾上腺皮质癌(ACC)患者的治疗具有挑战性,EDP-M(依托泊苷、多柔比星、顺铂联合米托坦)是标准方案。然而,它的毒性相当大,因此适当的支持性治疗对于尽可能减少副作用并维持细胞毒性药物的剂量强度至关重要。
我们根据布雷西亚 Spedali Civili 的肿瘤内科的经验,描述了 EDP-M 方案的主要副作用及其最佳管理方法。我们还讨论了在特定虚弱患者中使用 EDP-M 的方法,例如疾病范围广泛且表现状态(PS)较差的患者以及轻度肾功能不全的患者。
在分泌激素的 ACC 患者中,在开始 EDP-M 之前,必须使用肾上腺甾体生成抑制剂(如米托坦或奥西罗他汀)快速控制库欣综合征。使用粒细胞集落刺激因子进行中性粒细胞减少症的初级预防至关重要,应在第一个化疗周期中引入。在一个周期到另一个周期之间持续出现恶心和呕吐以及乏力时,应始终考虑可能由米托坦引起的肾上腺功能减退。对于 PS 较差的患者,顺铂 24 小时持续输注方案可能是一种初始选择,并且还可以降低轻度肾功能不全患者的肾毒性风险。
仔细、准确的支持性护理对于尽可能减轻 EDP-M 的副作用以及避免由于毒性导致患者必须减少剂量或推迟细胞毒性治疗至关重要,因为这会对这种化疗方案的疗效产生负面影响。