The number of effective
cytotoxic agents for the treatment of patients with metastatic adult
soft tissue sarcoma is limited, especially when patients have failed
anthracycline- and
ifosfamide-based
chemotherapy. For the subgroup of patients with inoperable gastrointestinal stromal tumour (GIST), progress has been made via the rapid development and approval of the targeted
therapy imatinib. Small round cell tumours (SRCTs), such as
Ewing's sarcoma/primitive neuroectodermal tumour, desmoplastic SRCT and
rhabdomyosarcoma, are
chemotherapy-sensitive and potentially curable
malignancies, which are treated with multimodality, dose-intensive, neoadjuvant protocols regardless of size or overt metastatic disease. Most other high-grade (grading >I), so-called 'adult type',
soft tissue sarcomas such as
fibrosarcoma,
liposarcoma, pleomorphic and
synovial sarcomas are treated with an
anthracycline-based regimen with or without
ifosfamide as front-line
therapy. In relapsed 'adult type'
soft tissue sarcomas,
trofosfamide,
gemcitabine and
trabectedin (
ecteinascidin 743) appear to be drugs associated with some activity and an acceptable toxicity profile. A high activity has been reported for the
taxanes, in particular for
paclitaxel, in vascular
sarcomas located in the scalp or face and in
Kaposi's sarcoma. It is interesting to note that the different drugs have particular effects in distinct subtypes of
soft tissue sarcoma; however, it should be taken into account that the number of patients included in the phase II trials is limited. The role of the newer agents (e.g.
epothilones,
brostallicin) is currently undefinable. Targeted
therapy inhibiting
vascular endothelial growth factor receptor,
epidermal growth factor receptor,
RAF kinase, c-KIT or
platelet-derived growth factor receptors will continue to be tested in GIST patients refractory to
imatinib and in other
sarcoma histologies.