Table 1 Targeted therapy clinical studies for soft tissue sarcoma (STS)

Tyrosine kinase inhibitors (TKIs)

Imatinib mesylate (IM)

c-Kit, PDGFR

Phase II study: 53.7% of patients with GISTs showed a partial response, 27.9% of patients showed stable disease, 13.6% of patients showed early resistance to imatinib, 5% of patients showed serious adverse events

[60]

Phase III study: confirmation of the effectiveness of imatinib as primary systemic therapy for patients with incurable GIST. No advantages to higher dose treatment were reported.

[61]

Sunitinib malate (SM)

VEGF-R1, VEGF-R2, VEGF-R3, c-Kit, PDGFR, Flt-3, CSF1, neurotrophic factor receptors

Phase III study: 7% of patients with GIST showed partial response, 58% had stable disease, 19% had progressive disease; 27.3 weeks was the time-to-tumor progression for sunitinib vs 6.4 weeks for placebo. Progression-free survival was similar.

[62]

Phase II study: 3-month progression-free rate of >40% for liposarcomas leiomyosarcomas

[63]

Phase II study: 52% of patients showed metabolic stable disease, 20% of patients achieved stable disease for at least 16 weeks, 47% of patients achieved partial response

[64]

Phase II study (current): SM activity in patients with certain subtypes of STS. The majority of these patients showed stable disease for 16 weeks.

[65]

Sorafenib

VEGF-R2, VEGF-R3, c-Kit, PDGFR, Raf/Mek/Erk

Phase II study: 14% of patients with angiosarcoma and 6% of patients with leiomyosarcoma had a response, 64% of patients developed intolerance at the drug dose used

[66]

Phase II study: 78% patients with vascular tumors showed disease stabilization

[67]

Phase II study (current): antitumor activity and acceptable toxicity profile in patients with antracycline-refractory STS

[68]

Pazopanib

VEGF-Rs

Phase II study: 12-week progression-free survival was reached by 44% patients with leiomyosarcoma, 49% of patients with synovial sarcomas, and 39% of patients with the other STS types

[69]

Nilotinib

BCR/ABL, c-Kit, PDGFR, CSF1R

Phase I study: nilotinib alone or in combination with imatinib was well tolerated and showed clinical activity in imatinib-resistant GIST patients

[70]

Mammalian target of rapamycin (mTOR) inhibitors

Tensirolimus

mTOR

Phase II study: moderate toxicity and limited clinical activity

[71]

Everolimus

mTOR

Phase II study: acceptable toxicity. Limited clinical activity in heavily pretreated patients with bone and soft tissue sarcomas. The efficacy in imatinib-refractory and sunitinib-refractory GIST is promising.

[72]

Ridaforolimus (AP23573)

mTOR

Phase I study: safety of the drug; 27% of patients showed stable disease.

[73]

Phase II study: 29% of clinical benefit rate. Prolongation of survival.

[74]

Phase III study (current)

[75]

Insulin-like growth factor (IGF) receptor antibodies

Figitumumab

IGF-1R

Phase I study: good tolerance of the drug

[76]

R1507

IGF-1R

Phase II study (current): R1507 is well tolerated. Significant activity has been observed in Ewing's sarcoma, RMS and OS with several dramatic responses seen in Ewing's sarcoma and RMS.

[77]

AMG479

IGF-1R

Phase I study: absence of severe toxicities

[78]

Mk-0646

IGF-1R

Phase I study (current)

[79]