New York University School of Medicine, New York, NY 10016, USA.
Anticancer Res. 2010 Feb;30(2):541-5.
Cisplatin is a highly effective chemotherapeutic agent against epithelial ovarian cancer but is associated with significant toxicities. SPI-77 is a liposomal pegylated formulation of cisplatin that was developed to reduce systemic toxicity and to better deliver cisplatin to tumors. We assessed the response rates and safety of SPI-77, in patients with recurrent epithelial ovarian cancer.
Patients were selected for having previously achieved a platinum treatment free interval of greater than 6 months (e.g. platinum-sensitive) and high potential of achieving responses when rechallenged with a platinum drug. SPI-77 was administered at a dose of 260 mg/m(2) every 21 days until disease progression.
Enrollment was terminated after 5 patients were treated because of concern with the adequacy of the formulation. Four out of the five patients had stable disease as best response. While no serious, unexpected adverse events occurred in spite of large cumulative doses of SPI-77, there were concerns related to the large lipid load and prolonged persistence of residual platinum in body stores.
The results of this study, although inconclusive regarding its primary endpoints, provide some important lessons for the development of similar liposomal platinum agents.
顺铂是一种针对上皮性卵巢癌的高效化疗药物，但具有显著的毒性。SPI-77 是一种顺铂的脂质体聚乙二醇化制剂，旨在降低全身毒性并更好地将顺铂递送至肿瘤部位。我们评估了 SPI-77 在复发性上皮性卵巢癌患者中的反应率和安全性。
选择这些患者的标准为先前铂类药物治疗无进展间期超过 6 个月（即铂类敏感），并且在再次使用铂类药物时具有较高的反应潜力。SPI-77 的剂量为 260mg/m2，每 21 天给药一次，直至疾病进展。
由于对制剂的充分性存在担忧，在治疗 5 例患者后即停止了入组。5 例患者中有 4 例的最佳反应为疾病稳定。尽管 SPI-77 的累积剂量很大，但未发生严重的、意外的不良事件，不过存在与大量脂质负荷和体内铂残留持续时间延长相关的问题。
尽管本研究的主要终点尚无定论，但为开发类似的脂质体顺铂制剂提供了一些重要经验。
