Phase 1 clinical trials for sarcomas: the cutting edge.

Abstract

PURPOSE OF REVIEW:

Few standard second-line treatment options exist for advanced sarcoma patients. Some of these patients are offered early-phase clinical trials involving targeted or nontargeted agents. This review outlines recent phase 1 trials involving sarcoma patients, explores current challenges and highlights future opportunities in sarcoma developmental therapeutics.

RECENT FINDINGS:

New molecularly targeted phase 1 studies have demonstrated efficacy in sarcomas. For instance, insulin-like growth factor-1 receptor (IGF1R) antibodies have produced single agent activity in Ewing's sarcoma. Other promising novel agents include an agonist for the apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) for chondrosarcoma, small molecule inhibitor crizotinib for anaplastic lymphoma kinase (ALK)-rearranged inflammatory myofibroblastic tumor, cedarinib for alveolar soft part sarcoma, and rexin-G, a tumor targeted retrovector for osteosarcoma. In addition, different combinations of chemotherapy in combination with newer agents such as trabectedin exhibited efficacy in advanced soft tissue sarcoma.

SUMMARY:

Patients with refractory sarcoma demonstrate benefit from treatment with targeted drugs even in the setting of phase 1 trials. Sarcomas that have a defined translocation and those that express specific activated kinases are particularly promising tumors for targeted therapy. The primary challenge is identifying the biomarkers predictive of response or resistance, matching them with specific patient histology, resulting in successful translation of biology into clinical benefit.

• Authors: Vivek Subbiah, Razelle Kurzrock
• Journal: Current opinion in oncology (Curr Opin Oncol) Vol. 23 Issue 4 Pg. 352-60 (Jul 2011) ISSN: 1531-703X [Electronic] United States
• PMID: 21519259 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Protein Kinase Inhibitors

Topics

• Antibodies, Monoclonal (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Bone Neoplasms (drug therapy)
• Clinical Trials, Phase I as Topic
• Humans
• Molecular Targeted Therapy
• Prognosis
• Protein Kinase Inhibitors (therapeutic use)
• Sarcoma (drug therapy)