ABSTRACT
BACKGROUND: We retrospectively analyzed data from patients who had been treated with trabectedin at our institution between April 2009 and August 2011. PATIENTS & METHODS: Data from 25 patients with recurrent soft tissue sarcoma (leiomyosarcoma: n = 8; liposarcoma: n = 5) were used to assess the efficacy and safety of trabectedin 1.5 mg/m(2) given every 3 weeks. RESULTS: Most patients (n = 14) had been heavily pretreated with ≥ 2 previous chemotherapy lines. Eight (32%) patients achieved a partial response according to dimensional and tumor density changes, and seven (28%) patients had stable disease for ≥ 3 months (clinical benefit rate = 60%; n = 15). Median progression-free survival was 6.4 months and overall survival 19.3 months. Common adverse events were fatigue, nausea, anemia and transient transaminase increases. CONCLUSION: Treatment with trabectedin is effective and well tolerated in heavily pretreated soft tissue sarcoma patients. Tapering dexamethasone courses and switching trabectedin administration to an every 4 weeks schedule effectively dealt with persistent fatigue without compromising effectiveness.
Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dioxoles/therapeutic use , Sarcoma/drug therapy , Sarcoma/pathology , Tetrahydroisoquinolines/therapeutic use , Adult , Aged , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Dioxoles/administration & dosage , Dioxoles/adverse effects , Female , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Staging , Retrospective Studies , Sarcoma/diagnosis , Sarcoma/mortality , Tetrahydroisoquinolines/administration & dosage , Tetrahydroisoquinolines/adverse effects , Trabectedin , Treatment Outcome , Young AdultABSTRACT
Metastatic melanoma has a very poor prognosis and systemic therapies - both cytotoxic and biological - have not improved outcome in this disease so far. For this reason, novel therapeutic strategies are urgently required. Angiogenesis represents a relevant process to modulate in melanoma, as pro-angiogenic ligands and their receptors are overexpressed and have been found to correlate with disease progression and prognosis. The angiogenic axis may be targeted at many different levels, which are still being defined. This article presents an overview of the importance of angiogenesis in melanoma and draws attention to some of the key molecules that are currently being targeted rationally within clinical studies. We discuss a number of anti-angiogenic and anti-vascular agents and their mechanisms of action. An overview of the efficacy and toxicity of these treatments in clinical trials performed so far in melanoma is presented and future directions for anti-angiogenic strategies in melanoma are considered.
