Thornton Katherine A
Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, Baltimore, MD, USA.
Core Evid. 2010 Jun 15;4:191-8. doi: 10.2147/ce.s5993.
Soft tissue sarcoma accounts for less than 1% of all malignant neoplasms and is comprised of a very heterogeneous group of tumors with over 50 different subtypes. Due to its diversity and rarity, developing new therapeutics has been difficult, at best. The standard of care in the treatment of advanced and metastatic disease over the last 30 years has been doxorubicin and ifosfamide, either alone or in combination. There has been significant focus on developing new therapeutics to treat primary and metastatic disease. Trabectedin (ecteinascidin-743) is a tetrahydroiso-quinoline alkaloid which has been evaluated in the treatment of metastatic soft tissue sarcoma.
To review the current evidence for the therapeutic use of trabectedin in patients with soft tissue sarcoma.
Five phase I studies in patients with solid tumors, all of which include sarcoma patients, evaluating the dosing and toxicity of trabectedin were performed with efficacy being evaluated as a secondary endpoint. Additionally, there are four phase I trials evaluating trabectedin in combination with frontline therapeutic drugs in soft tissue sarcoma. Four phase II studies were performed in soft-tissue sarcoma patients with objective response rates ranging from 3.7% to 17.1%. Additionally, in two compassionate use trials, objective response rates between 14% and 51% were seen, the largest response resulting from a study specifically focusing on liposarcoma.
Trabectedin is a potential therapeutic option for the management of soft-tissue sarcoma. It appears to have specific activity in a select group of histologies, most notably myxoid/round cell liposarcoma. Although it would be helpful to study the use of trabectedin in a randomized, controlled fashion, the relative rarity of soft-tissue sarcoma, and heterogeneity of the histologic subtypes, makes phase III trials a difficult prospect.
软组织肉瘤占所有恶性肿瘤的比例不到1%，由超过50种不同亚型的高度异质性肿瘤组成。由于其多样性和罕见性，开发新的治疗方法一直非常困难。在过去30年中，晚期和转移性疾病的治疗标准一直是阿霉素和异环磷酰胺，单独使用或联合使用。人们一直非常关注开发治疗原发性和转移性疾病的新疗法。曲贝替定（ecteinascidin-743）是一种四氢异喹啉生物碱，已被用于评估其在转移性软组织肉瘤治疗中的效果。
综述曲贝替定治疗软组织肉瘤患者的现有证据。
对实体瘤患者进行了五项I期研究，所有研究均包括肉瘤患者，评估曲贝替定的剂量和毒性，并将疗效作为次要终点进行评估。此外，还有四项I期试验评估曲贝替定与软组织肉瘤一线治疗药物联合使用的情况。对软组织肉瘤患者进行了四项II期研究，客观缓解率在3.7%至17.1%之间。此外，在两项同情用药试验中，观察到客观缓解率在14%至51%之间，最大缓解率来自一项专门针对脂肪肉瘤的研究。
曲贝替定是治疗软组织肉瘤的一种潜在治疗选择。它似乎在特定的一组组织学类型中具有特定活性，最显著的是黏液样/圆形细胞脂肪肉瘤。尽管以随机对照方式研究曲贝替定的使用会有所帮助，但软组织肉瘤的相对罕见性以及组织学亚型的异质性使得进行III期试验前景困难。
