Trabectedin in pretreated pediatric patients with relapsed or progressive advanced sarcomas: Toxicity and efficacy.

Abstract

e20005 Background: Patients with advanced or metastatic soft tissue and bone sarcomas whose disease progresses after standard chemotherapy (CT) have few options and limited life expectancy. Trabectedin, an alkaloid derived from the sea squirt Ecteinascidia turbinate, has proven activity against some soft tissue (STS) and bone sarcomas. In pediatric patients there is limited information about its efficacy and toxicity profile. Purpose: To describe the toxicity and efficacy of trabectedin in a group of relapsed/refractory pediatric sarcomas. Methods: From January 2009 to December 2011, four relapsed/refractory pediatric sarcoma patients were treated with trabectedin in the Hospital Infantil de Mexico Federico Gomez. Trabectedin was administered as a 24-hour IV infusion every 21 days. Dose levels were 1.3-1.5 mg/m2. All received dexamethasone premedication. Grade 3-4 toxicity was evaluated according to the NCI criteria. Results: Diagnoses included a metastatic Ewing sarcoma, a triton tumor (TT), a metastatic alveolar soft tissue sarcoma and a phylodes sarcoma. All had previously failed to 2 or 3 CT regimens. In 3 patients radiotherapy had also been used and multiple surgical procedures were performed to treat recurrences, before trabectedin. A total of 13 courses of trabectedin were administered. Nausea/vomiting and fatigue were seen in 61.5% of the courses. Laboratory abnormalities included anemia (30.6%), neutropenia (15.3%), ALT (15.3%), AST (15.3%) and GGT (7.7%) elevations and lipasemia/amilasemia (7.7%). One patient presented significant transaminasemia, pancreatitis (probably steroid-related) and died after the first course due to IDC. The TT case, who had a massive unresectable lesion, exhibited a significant response, although her tumor progressed after 4 cycles and eventually died; none of the other patients responded to trabectedin. Conclusions: Trabectedin was generally well tolerated; however we faced a fatal event that might be not trabectedin related. The response observed in the TT case is an interesting finding considering the poor CT response of this aggressive tumor.