Sarcoma Unit, Royal Marsden Hospital, London, UK.
Curr Treat Options Oncol. 2011 Mar;12(1):32-45. doi: 10.1007/s11864-011-0140-x.
Doxorubicin and ifosfamide are the two chemotherapy drugs that have consistently demonstrated activity in "soft tissue sarcoma" (STS). However, STS is not a homogeneous entity but an umbrella term for a diverse group of more than 40 differing subtypes; each with distinct underlying biology, natural history and response to treatments. The accuracy of the histological and in some cases molecular diagnosis is therefore critical to the optimal treatment of these patients. Leiomyosarcomas have been shown to have limited responsiveness to ifosfamide, but both the combination of gemcitabine and docetaxel, and single agent trabectedin have shown considerable activity in this tumour group. Differences in responses to chemotherapy are seen for leiomyosarcomas of different anatomical sites with uterine leiomyosarcoma demonstrating considerable chemo-responsiveness, whereas vascular leiomyosarcomas appearing far less sensitivity. There is considerable variation in the sensitivity of the three main subtypes of liposarcomas, with well-differentiated liposarcomas showing generalised chemo-resistance through to the impressive responses seen anthracyclines and to trabectedin with the myxoid subtype. Angiosarcomas have demonstrated considerable sensitivity to paclitaxel, a drug that has little activity outside of vascular sarcomas, and liposomal doxorubicin appears to have a particular indication in this subtype. Synovial sarcomas appear to have significant sensitivity to ifosfamide, even on re-challenge. On the other hand, there are subtypes that are chemo-resistant, including gastrointestinal stromal tumour, alveolar soft part sarcoma and clear cell sarcoma, and chemotherapy plays no role in their management. Whilst it is obvious that there is a need to find new agents to treat these tumours, there is an imperative to make sure that the studies that evaluate their "efficacy" are designed to determine the efficacy within differing histiotypes through stratification by histological subtype, or enrichment strategies to ensure that "activity" is not diluted by unresponsive or even chemo-resistant tumour types.
多柔比星和异环磷酰胺是两种在“软组织肉瘤”（STS）中始终表现出活性的化疗药物。然而，STS 不是一个同质实体，而是一个涵盖 40 多种不同亚型的伞状术语；每个亚型都具有不同的基础生物学、自然史和对治疗的反应。因此，组织学和在某些情况下分子诊断的准确性对于这些患者的最佳治疗至关重要。平滑肌肉瘤对异环磷酰胺的反应有限，但吉西他滨和多西他赛联合用药以及单药 trabectedin 均在该肿瘤组中表现出相当大的活性。不同解剖部位的平滑肌肉瘤对化疗的反应存在差异，子宫平滑肌肉瘤表现出相当大的化疗反应性，而血管平滑肌肉瘤则表现出较低的敏感性。三种主要脂肪肉瘤亚型的敏感性存在很大差异，高分化脂肪肉瘤表现出普遍的化疗耐药性，直至蒽环类药物和 trabectedin 表现出令人印象深刻的反应，黏液样亚型也是如此。血管肉瘤对紫杉醇表现出相当大的敏感性，这种药物在血管肉瘤之外几乎没有活性，而脂质体多柔比星似乎在这种亚型中有特定的适应证。滑膜肉瘤对异环磷酰胺似乎有明显的敏感性，即使是在重新挑战时也是如此。另一方面，也有一些亚型对化疗耐药，包括胃肠道间质瘤、肺泡软组织肉瘤和透明细胞肉瘤，化疗在其治疗中不起作用。虽然显然需要寻找新的药物来治疗这些肿瘤，但当务之急是确保评估其“疗效”的研究通过组织学分型分层或富集策略来确定不同组织类型中的疗效，以确保“活性”不会因无反应甚至化疗耐药的肿瘤类型而稀释。
