Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients With Progressive Sarcomas of Soft Tissues Refractory to Chemotherapy

Abstract

ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.

Phase I trial of weekly trabectedin (ET-743) and gemcitabine in patients with advanced solid tumors

“…Gemcitabine has also shown activity in phase II trials as a single agent and in combination with docetaxel in patients with advanced sarcomas, particularly leiomyosarcoma [13,19,20,23]. Trabectedin has demonstrated efficacy as a single agent in patients with sarcoma [7,8,17,26,39] and has shown promise in phase I trials against a variety of malignancies when given in combination with capecitabine [9], doxorubicin [1] or pegylated liposomal doxorubicin [3], but nearly all previous studies have used an every-3-week schedule. Although dose level 3 contained an approved gemcitabine dose of 1,000 mg/m 2 per week, the highest dose of trabectedin evaluated in combination with this gemcitabine dose was 0.4 mg/m 2 per week.…”

“…The concentration of trabectedin was measured in plasma samples collected prior to dosing and at 30 min, 2, and 3 h, 50 min, 4,5,8,11,27,51, and 168 h after the start of the trabectedin infusion. On cycle 1 days 8 and 15, and cycle 2 days 1, 8, and 15, samples were collected pre-dose, at 20 min (10 min prior to the end of the gemcitabine infusion), and 200 min (10 min prior to the end of the trabectedin infusion).…”

“…In clinical trials, single-agent trabectedin in a variety of administration schedules has achieved clinical responses in patients with a variety of tumor types, including ovarian cancer, osteosarcoma, soft tissue sarcoma, and breast cancer [7,8,11,16,17,21,30,39,40]. Recent data suggest that single-agent trabectedin may become a standard of care in advanced pre-treated sarcomas, with clinical benefit observed in patients with liposarcoma and leiomyosarcoma following failure of all conventional treatment options [26].…”

Systemic Therapy in Soft Tissue Sarcomas: Past, Present and Future

“…The recommended dose is 1.5 g/m2 over 24 h as a continous infusion (central line) once every 3 weeks. Disease stabilization was seen in up to 60% for synovial sarcomas and leiomyosarcomas [21,22]. Promising results were also seen in myxoid/round cell liposarcoma in a retrospective study.…”

Trabectedin in patients with pre-treated advanced soft tissue sarcoma: a retrospective single center analysis

“…All patients were previously treated with chemotherapy. R Re es su ul lt ts s: : 120 courses of trabectedin were given (median 4, range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. We were able to assess the response in 24 patients.…”