注射用曲贝替定（他比特定、Yondelis）

【Function and indication】
Yondelis for injection is a new non-platinum drug developed and produced by Zeltia Pharmaceuticals of Spain. It was approved for the treatment of advanced soft tissue sarcoma in September 2007 and has now been approved by European regulators for the treatment of ovarian cancer.

【Model and specification】
1mg injection

【Usage and dosage】
1.5mg/m2, continuous 24h intravenous drip, once a month, three times a course of treatment.

【Clinical study】
An international study showed that trabectedin combined with polyethylene glycol liposomal doxorubicin (PLD) for the second-line treatment of recurrent ovarian cancer can significantly improve progression-free survival (PFS) and overall response rate (ORR) compared with PLD alone, and the patient tolerance is acceptable. The relevant paper was recently published in the Journal of Clinical Oncology [J Clin Oncol 2010, 28(19): 3017].

The study subjects were aged ≥18 years and stratified by performance status (0-1 points vs. 2 points) and platinum sensitivity. Patients were randomly assigned to receive PLD 30 mg/m2 intravenously every 3 weeks, followed by 1.1 mg/m2 of trabectedin infused for 3 hours, or PLD 50 mg/m2 every 4 weeks. The primary endpoint was progression-free survival (PFS), which was assessed by independent radiological review.

A total of 672 patients were included in the study, including 337 in the trabectedin/PLD group and 335 in the PLD group, who had previously received platinum-based first-line chemotherapy. The median PFS in the trabectedin/PLD group and the PLD group were 7.3 months and 5.8 months, respectively [hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.65-0.96, P=0.0190]. The median PFS of patients sensitive to platinum in the two groups was 9.2 months and 7.5 months, respectively (HR was 0.73, 95% CI was 0.56-0.95, P=0.0170). The total response rate (ORR) obtained by the two groups of patients was 27.6% and 18.8% (P=0.0080), and this value was 35.3% and 22.6% in platinum-sensitive patients, respectively (P=0.0042). There was no statistical difference in ORR, PFS and overall survival (OS) between the two groups of patients who were not sensitive to platinum. Neutropenia was more common in the trabectedin/PLD group, and grade 3-4 transaminase elevation was also more common, but it was transient and non-cumulative. The incidence of hand-foot syndrome and mucositis in the trabectedin/PLD group was lower than that in the PLD group.

[Adverse reactions and contraindications] Electrocardiogram changes, tachycardia, intestinal obstruction, lung infection, diarrhea, neutropenia, acute renal failure, mild anemia, pharyngitis, mouth ulcers, nausea and vomiting, etc.

[Drug interactions] Trabectedin (Johnson & Johnson Pharmaceuticals) is the first marine-derived anti-tumor drug, a semi-synthetic product of tetrahydroquinoline alkaloids extracted from sea squirts. In addition to blocking the differentiation of tumor cells in the G1/G2 cycle, it can also inhibit the secretion of vascular endothelial growth factor (VEGF) and the expression of VEGF receptor (VEGFR)-1. In 2004, it was designated as an orphan drug for the treatment of acute lymphoblastic leukemia, soft tissue sarcoma and ovarian cancer in Europe and the United States.

[Storage] Protect from light and store at low temperature of 2°-8°

[Manufacturer] Yondelis for injection was developed by Zeltia Pharmaceuticals of Spain.