Berruti A, Terzolo M, Pia A, Angeli A, Dogliotti L
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Italy.
Cancer. 1998 Nov 15;83(10):2194-200.
The use of either mitotane or chemotherapy in the treatment of advanced adrenocortical carcinoma (ACC) has led to scanty and controversial results. The recent finding that mitotane is able to reverse in vitro multidrug resistance has provided a rational basis for combining this agent with cytotoxic drugs. The association of mitotane with etoposide, doxorubicin, and cisplatin (EDP) in the treatment of patients with advanced, inoperable ACC was tested in an Italian multicenter Phase II trial.
Twenty-eight patients (18 women and 10 men; median age, 47 years; range, 27-65 years) with measurable disease were enrolled in the study and evaluated for toxicity and response. There were 18 patients with clinical and/or biochemical evidence of steroid hypersecretion. An EDP schedule (etoposide 100 mg/m2 on Days 5-7, doxorubicin 20 mg/m2 on Days 1 and 8, and cisplatin 40 mg/m2 on Days 1 and 9) was administered intravenously every 4 weeks; concomitantly, patients were given up to 4 g/day of oral mitotane or the maximum tolerated dose, without any interruption between chemotherapy cycles.
According to World Health Organization criteria, complete response was achieved in 2 patients and partial response in 13, for an overall response rate of 53.5% (95% CI, 35-72%). Stable disease was observed in 8 patients and progressive disease in 5. Responses occurred in patients with both functioning and nonfunctioning tumors, and more often in those bearing lymph node and lung metastases. Time to progression in responding patients was 24.4 months. Generally, the EDP regimen was well tolerated. Only 4 patients received reduced doses, whereas 3 discontinued early chemotherapy due to toxicity. The addition of mitotane increased neurologic and gastrointestinal side effects. Due to these additional toxicities, only 9 patients regularly took the drug at the planned dose (4 g/day); 11 received the maximum tolerated dose of 3 g/day, 6 received 2 g/day, and 1 received 1 g/day. Mitotane was also responsible for raised serum levels of cholesterol and triglycerides. A complete hormone response (normalization of altered biochemical parameters) was observed in 9 of 16 evaluable patients with functioning tumors.
EDP plus mitotane combination chemotherapy appears to be active and manageable treatment for patients with advanced ACC.
米托坦或化疗用于治疗晚期肾上腺皮质癌（ACC）的疗效甚微且存在争议。最近发现米托坦能够逆转体外多药耐药性，这为将该药物与细胞毒性药物联合使用提供了合理依据。在一项意大利多中心II期试验中，对米托坦与依托泊苷、阿霉素和顺铂（EDP）联合用于治疗晚期、无法手术切除的ACC患者进行了测试。
28例（18例女性和10例男性；中位年龄47岁；范围27 - 65岁）有可测量病灶的患者入组本研究，并对毒性和反应进行评估。有18例患者有类固醇分泌过多的临床和/或生化证据。每4周静脉给予一次EDP方案（第5 - 7天给予依托泊苷100mg/m²，第1天和第8天给予阿霉素20mg/m²，第1天和第9天给予顺铂40mg/m²）；同时，给予患者口服米托坦每日最高4g或最大耐受剂量，化疗周期之间不中断。
根据世界卫生组织标准，2例患者达到完全缓解，13例患者达到部分缓解，总缓解率为53.5%（95%CI，35 - 72%）。8例患者病情稳定，5例患者病情进展。有功能和无功能肿瘤患者均出现缓解，且在有淋巴结和肺转移的患者中更常见。缓解患者的疾病进展时间为24.4个月。总体而言，EDP方案耐受性良好。只有4例患者接受了减量，而3例患者因毒性提前停止化疗。添加米托坦增加了神经和胃肠道副作用。由于这些额外的毒性，只有9例患者按计划剂量（4g/天）规律服用该药物；11例患者接受了3g/天的最大耐受剂量，6例患者接受了2g/天，1例患者接受了1g/天。米托坦还导致血清胆固醇和甘油三酯水平升高。16例可评估的有功能肿瘤患者中有9例出现了完全激素反应（改变的生化参数恢复正常）。
EDP联合米托坦的联合化疗似乎是晚期ACC患者的有效且可管理的治疗方法。
