Yondelis

Trabectedin

Treatment of advanced soft tissue sarcoma in adults after failure of anthracyclines & ifosfamide, or who are unsuited to receive these agents. In combination w/ pegylated liposomal doxorubicin (PLD) for the treatment of patients w/ relapsed platinum-sensitive ovarian cancer.

Premed w/ corticosteroids eg, dexamethasone 20 mg IV 30 min prior to PLD (in combination therapy) or Yondelis (in monotherapy). Soft tissue sarcoma 1.5 mg/m² as an IV infusion over 24 hr w/ a 3-wk interval between cycles. Ovarian cancer 1.1 mg/m² every 3 wk as a 3-hr infusion, immediately after PLD 30 mg/m².

Hypersensitivity. Concurrent serious or uncontrolled infection. Concomitant use w/ yellow fever vaccine. Lactation.

Associated w/ grades 3 or 4 neutropenia & thrombocytopenia. Reports of rhabdomyolysis; liver function test abnormalities; hypersensitivity reactions; capillary leak syndrome. Caution in patients w/ hepatic impairment. Do not treat patients w/ elevated serum bilirubin levels at baseline; renal insufficiency (CrCl <30 mL/min for monotherapy, <60 mL/min for the combination regimen); baseline neutrophil counts <1,500 cells/mm³ & platelet counts <100,000 cells/mm³; creatine phosphokinase (CPK) >2.5 x ULN. Monitor haematological parameters, bilirubin, alkaline phosphatase, aminotransferases & CPK wkly during the 1st 2 cycles of therapy, & at least once between treatments in subsequent cycles. Monitor patients for cardiac-related adverse events or myocardial dysfunction. Anti-emetic prophylaxis w/ corticosteroids eg, dexamethasone must be administered to all patients. Use of central venous access is strongly recommended. Avoid extravasation. Avoid co-administration w/ potent CYP3A4 inhibitors; alcohol. Caution if concomitantly taken w/ medicinal products associated w/ hepatotoxicity. Not recommended w/ phenytoin or live attenuated vaccines. May impair ability to drive or operate machinery. Women of childbearing potential must use effective contraception during treatment & 3 mth thereafter. Men in fertile age must use effective contraception during treatment & 5 mth after treatment. May cause serious birth defects when administered during pregnancy. Should not be used in childn <18 yr w/ paed sarcomas.

Neutropenic infection; neutropenia, thrombocytopenia, anaemia, leukopenia; decreased appetite; insomnia; headache; dyspnoea, cough; abdominal pain, nausea, vomiting, constipation, diarrhoea, stomatitis; increased ALT, AST, blood alkaline phosphatase, blood bilirubin; palmar-plantar erythrodysaesthesia syndrome; arthralgia, back pain, increased blood CPK; fatigue, pyrexia, oedema, mucosal inflammation; increased blood creatinine, decreased blood albumin. Sepsis; febrile neutropenia; hypersensitivity; dehydration, hypokalaemia; dizziness, dysgeusia, peripheral sensory neuropathy, syncope; palpitations, left ventricular dysfunction; hypotension, flushing; pulmonary embolism; dyspepsia; increased γ-glutamyltransferase; rash, alopecia, skin hyperpigmentation; myalgia; inj site reactions; decreased wt.

Increased plasma conc w/ potent CYP3A4 inhibitors (eg, oral ketoconazole, fluconazole, ritonavir, clarithromycin or aprepitant). Reduced plasma conc w/ strong CYP3A4 inducers (eg, rifampicin, phenobarb, St. John's Wort). Increased risk of hepatotoxicity w/ alcohol. Altered distribution &/or elimination w/ P-gp inhibitors eg, cyclosporine & verapamil.

Cytotoxic Chemotherapy

L01CX01 - trabectedin ; Belongs to the class of other plant alkaloids and natural products. Used in the treatment of cancer.

P₁S₁S₃