VIAL (concentrate for solution for infusion): 1 x 1 mg.
Must be administered under the supervision of a physician experienced in the use of chemotherapy.
The recommended dose is 1.5 mg/m2
body surface area, administered as an intravenous infusion over 24 hours with a three-week interval between cycles. Administration through a central venous line is strongly recommended. All patients must receive corticosteroids, e.g. 20 mg of dexamethasone I.V. 30 minutes prior to Yondelis; not only as anti-emetic prophylaxis, but also because it appears to provide hepatoprotective effects. Additional anti-emetics may be administered as needed.
Treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. Efficacy data are based mainly on liposarcoma and leiomyosarcoma patients.
Hypersensitivity to trabectedin or to any of the excipients. Concurrent serious or uncontrolled infection. Lactation. Combination with yellow fever vaccine.
The following criteria are required to allow treatment: Absolute neutrophil count (ANC)> 1,500/mm3
; platelet count> 100,000/mm3
; bilirubin< upper limit of normal (ULN); alkaline phosphatase <2.5 x ULN (consider hepatic isoenzymes 5-nucleotidase or GGT, if the elevation could be osseous in origin); albumin> 25 g/l; alanine aminotransferase (ALT) and aspartate aminotransferase (AST)< 2.5 x ULN; creatinine clearance>30 ml/min; creatine phosphokinase (CPK)< 2.5 x ULN; hemoglobin> 9 g/dl. The same criteria as above must be met prior to re-treatment. Otherwise treatment must be delayed for up to 3 weeks until the criteria are met. Additional monitoring of hematological parameters bilirubin, alkaline phosphatase, aminotransferases and CPK should occur weekly during the first two cycles of therapy, and at least once between treatments in subsequent cycles.
Prior to re-treatment, patients must fulfil the baseline criteria defined above. If any of the following events occur at any time between cycles, the dose must be reduced one level. See prescribing information for full details. Duration of treatment: In clinical trials, there were no pre-defined limits to the number of cycles administered. No cumulative toxicities have been observed in patients treated with multiple cycles. Pediatric patients: The safety and efficacy have not yet been established. Elderly patients: No specific studies in elderly patients have been performed. No relevant differences in the safety profile were seen in this patient population.
Impaired hepatic function: No studies with the proposed regimen have been conducted in patients with liver dysfunction. However, special caution is advised and dose adjustments may be necessary in these patients since systemic exposure is probably increased and the risk of hepatotoxicity might be increased. Patients with elevated bilirubin must not be treated.
Impaired renal function: Studies including patients with renal insufficiency (creatinine clearance < 30 ml/min) have not been conducted and therefore Yondelis must not be used in this patient population. See prescribing information for full details.
Pregnancy and lactation
: Should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the fetus and be monitored carefully. If used at the end of pregnancy, potential adverse reactions should be monitored carefully in the newborns. Men in fertile age and women of childbearing potential must use effective contraception during treatment and 3 months thereafter for women and immediately inform the treating physician if a pregnancy occurs, and 5 months after treatment for men. Trabectedin can have genotoxic effects. Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy. If pregnancy occurs during treatment the possibility of genetic counselling should be considered. Genetic counselling is also recommended for patients wishing to have children after therapy. Lactation: It is not known whether trabectedin is excreted in human milk, and the excretion in milk has not been studied in animals. Breast-feeding is contraindicated during treatment and 3 months thereafter.
Most frequent adverse reactions: Neutropenia, thrombocytopenia, anemia. AST/ALT increases, hyperbilirubinemia. See prescribing information for full details.
CYP3A4 inhibitors (e.g. ketoconazole, fluconazole ritonavir, clarithromycin or aprepitant), potent CYP3A4 inducers (e.g. rifampicin, phenorbarbital, Saint John's Wort). Alcohol consumption must be avoided during treatment.