Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors
Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors
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DOI：
10.1177/000348940411300312
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发表时间：
2004-03-01
影响因子：
1.4
通讯作者：
Chauffert, B
中科院分区：
文献类型：
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作者：
Duvillard, C;Romanet, P;Chauffert, B
局部复发的头颈部肿瘤通常不适合手术和/或放疗再治疗，全身化疗的疗效较差。理论上，肿瘤内化疗可以获得更大的抗癌药物蓄积和疗效，全身毒性更低。在实验研究中，肾上腺素已被证明可以增加肿瘤内顺铂的浓度和抗肿瘤作用。14例局部复发性头颈部肿瘤患者（中位年龄58.7岁）被纳入该II期试验。复发性肿瘤（鳞状细胞癌）位于舌、口咽或颈部淋巴结。既往治疗为手术和/或放疗伴或不伴静脉化疗。入选标准包括东部肿瘤协作组/世界卫生组织体能状态为0、1或2，预期生存期>3个月，心脏、肾脏、肝脏和骨髓功能良好，无凝血障碍或颈动脉浸润。从1998年11月至2000年7月，对14例患者进行了50次顺铂-肾上腺素瘤内注射（平均每例患者3.6次注射;范围1至5次注射）。患者接受顺铂（1 mg/mL;最大剂量，50 mg）治疗，注射体积对应于肿瘤体积（1 mL/cm（3）肿瘤;最大体积，50 mL）。以0.02 mg/mL的浓度加入依匹林。每2至3周在肿瘤的不同位置重复瘤内注射以获得均匀分布。通过临床检查和计算机断层扫描评价肿瘤缓解。14例患者中登记了8例客观缓解。4例完全缓解，4例部分缓解。至疾病进展的平均时间为11.5 ± 8.9周。局部不良反应为注射部位的一过性疼痛、肿胀和红斑。未观察到肾毒性、神经毒性或耳毒性。肿瘤内注射顺铂和肾上腺素水溶液对复发性头颈癌具有明确的抗肿瘤活性，局部耐受性可接受，除注射时出现一过性心动过速和高血压外，无重大全身毒性作用。
Local relapses of head and neck tumors are not often eligible for surgical and/or radiotherapy retreatment, and the efficacy of systemic chemotherapy is poor. A greater accumulation and efficacy of anticancer drugs with lower systemic toxicity is theoretically obtained with intratumoral chemotherapy. In experimental studies, epinephrine has been shown to increase the concentration and antitumor effect of intratumoral cisplatin. Fourteen patients with locally recurrent head and neck tumors (median age, 58.7 years) were included in this phase 2 trial. Recurrent tumors (squamous cell carcinomas) were located on the tongue, oral pharynx, or cervical nodes. Prior therapy was surgery and/or radiotherapy with or without intravenous chemotherapy. Inclusion criteria included an Eastern Cooperative Oncology Group/World Health Organization performance status of 0, 1, or 2, an anticipated survival of >3 months, adequate cardiac, kidney, liver, and bone marrow function, and no coagulopathy or carotid invasion. Fifty intratumoral injections of cisplatin-epinephrine (average, 3.6 injections per patient; range, 1 to 5 injections) were given to the 14 patients from November 1998 to July 2000. Patients were treated with cisplatin (1 mg/mL; maximum dose, 50 mg) at an injection volume corresponding to the tumor volume (1 mL/cm(3) of tumor; maximum volume, 50 mL). Epinephrine was added at a concentration of 0.02 mg/mL. Intratumoral injections were repeated every 2 to 3 weeks at different locations in the tumors to obtain a homogeneous distribution. Tumor response was evaluated by clinical examination and computed tomography. Eight objective responses were registered among the 14 patients. Four were complete responses, and 4 were partial responses. The average time to disease progression was 11.5 +/- 8.9 weeks. Local adverse effects were transient pain, swelling, and erythema at the site of the injection. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Intratumoral injection of cisplatin and epinephrine in an aqueous solution has a definite antitumor activity in recurrent head and neck cancer with acceptable local tolerance and no major systemic toxic effects except for transient tachycardia and high blood pressure at the time of injection.