Chao Ta-Chung, Wang Wei-Shu, Yen Chueh-Chuan, Chiou Tzeon-Jye, Liu Jin-Hwang, Chen Po-Min
Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC.
Cancer Invest. 2003;21(6):837-47. doi: 10.1081/cnv-120025086.
Doxorubicin is considered among the most active single agents used against advanced breast cancer. Recent advances in the design of liposomes as carriers of cytotoxic drugs have resulted in a new formulation of doxorubicin with improved pharmacokinetic and tumor-localizing properties. The objectives of this dose-escalating pilot study were to evaluate the efficacy and safety of the sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) for the treatment of metastatic breast cancer. Lipo-Dox was given at the dosage of 45 mg/m2 over 1 hr of intravenous infusion every 4 weeks initially and could be escalated up to a maximum of 60 mg/m2. Response was assessable in 17 of 19 intent-to-treat patients. An objective response was achieved in 41.2% (95% confidence interval: 17.8%-64.6%) of patients (5.9% complete response and 35.3% partial response), and 23.5% had stable disease. Median time to disease progression was 163 days. Major treatment-related toxicities included neutropenia, stomatitis, and skin toxicity in this dose-escalation program. Impressively, no grade 4 toxicities have ever been observed. The only grade 3 nonhematological toxicity ever to occur was reversible skin toxicity, presented as palmar-plantar erythrodysthesia. No severe nausea/vomiting, wig-necessary alopecia, or significant cardiac function change were encountered. In conclusion, Lipo-Dox is shown by this first reported pilot study to be an active agent for treatment of advanced breast cancer with a safety profile that differs markedly from free doxorubicin. The dosage of 45-60 mg/m2 every 4 weeks was well tolerated. Because myelosuppression and other nonhematological toxicities associated with Lipo-Dox were generally mild and acceptable, further assessment of this drug particularly in combination with other chemotherapeutic drugs in the management of early or advanced breast cancer is suggested.
阿霉素被认为是治疗晚期乳腺癌最有效的单一药物之一。作为细胞毒性药物载体的脂质体设计方面的最新进展，已产生了一种具有改善的药代动力学和肿瘤定位特性的阿霉素新制剂。这项剂量递增的初步研究的目的是评估空间稳定的聚乙二醇化脂质体阿霉素（Lipo-Dox）治疗转移性乳腺癌的疗效和安全性。Lipo-Dox最初每4周静脉输注1小时，剂量为45mg/m²，最高可增至60mg/m²。19例意向性治疗患者中有17例可评估反应。41.2%（95%置信区间：17.8%-64.6%）的患者获得客观反应（5.9%完全缓解，35.3%部分缓解），23.5%病情稳定。疾病进展的中位时间为163天。在这个剂量递增方案中，主要的治疗相关毒性包括中性粒细胞减少、口腔炎和皮肤毒性。令人印象深刻的是，从未观察到4级毒性。唯一发生过的3级非血液学毒性是可逆的皮肤毒性，表现为手足红斑性感觉异常。未出现严重恶心/呕吐、导致需要戴假发的脱发或明显的心功能改变。总之，这项首次报道的初步研究表明，Lipo-Dox是治疗晚期乳腺癌的一种有效药物，其安全性与游离阿霉素明显不同。每4周45-60mg/m²的剂量耐受性良好。由于与Lipo-Dox相关的骨髓抑制和其他非血液学毒性一般较轻且可接受，建议进一步评估该药物，特别是在早期或晚期乳腺癌治疗中与其他化疗药物联合使用时。
