晚期癌症伴肝脏广泛转移患者肝动脉内顺铂联合静脉注射脂质体多柔比星的Ⅰ期临床试验。
Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement.
机构信息
Phase I Program, Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
出版信息
Cancer Chemother Pharmacol. 2010 Nov;66(6):1087-93. doi: 10.1007/s00280-010-1266-4. Epub 2010 Mar 4.
PURPOSE
We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement.
METHODS
Patients were treated with HAI cisplatin 100-125 mg/m(2) (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20-35 mg/m(2) IV (day 1) every 28 days. A "3 + 3" study design was used.
RESULTS
Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m(2) level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m(2) and systemic doxil 35 mg/m(2) dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD.
CONCLUSION
The MTD was HAI cisplatin 100 mg/m(2) and systemic doxil 35 mg/m(2). This regimen demonstrated antitumor activity, especially in breast cancer.
目的
我们进行了一项Ⅰ期研究，评估了经肝动脉输注（HAI）顺铂联合全身化疗治疗晚期癌症伴肝脏广泛转移患者的疗效。
方法
患者接受 HAI 顺铂 100-125mg/m²（并给予 3000IU 肝素）和脂质体阿霉素（多柔比星脂质体）20-35mg/m²（第 1 天），每 28 天一次。采用“3+3”设计方案。
结果
共 30 例患者接受了治疗（中位年龄 56 岁）。诊断包括乳腺癌（n=11）、结直肠癌（n=8）、眼黑色素瘤（n=4）和其他（n=7）。患者中位接受过 5 种治疗方案。最大耐受剂量（MTD）为 100/35mg/m² 水平。顺铂 125mg/m² 和全身多柔比星 35mg/m² 剂量水平时，出现 4 例（2 例患者）的 4 级中性粒细胞减少症和 1 例（1 例患者）的 4 级血小板减少症为剂量限制毒性。最常见的毒性为恶心/呕吐和乏力。可评估疗效的 24 例患者中，4 例（17%）患者部分缓解（PR），7 例（29%）患者疾病稳定（SD）≥4 个月。11 例乳腺癌患者中，3 例（27%）患者 PR，5 例（45%）患者 SD≥4 个月。4 例眼黑色素瘤患者中，1 例 PR，1 例 SD 4 个月。1 例肝细胞癌患者 SD 4 个月。MTD 治疗的 12 例可评估患者中，2 例（17%）患者 PR，5 例（42%）患者 SD。
结论
MTD 为 HAI 顺铂 100mg/m² 和全身多柔比星 35mg/m²。该方案显示出抗肿瘤活性，尤其对乳腺癌患者有效。
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