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.