Indications: Canadian labeling: Ovarian cancer: Treatment of relapsed platinum-sensitive ovarian cancer (in combination with doxorubicin liposomal)

Soft tissue sarcoma: Treatment of metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) after failure of prior anthracycline and ifosfamide chemotherapy.

Cautions: measure creatine kinase, renal function and hepatic function before starting, monitor haematological and hepatic parameters weekly during first 2 cycles and at least once between treatments in subsequent cycles; concomitant use with hepatotoxic drugs (avoid alcohol). Note: High alert medication: This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Contra-indications: Hypersensitivity to trabectedin or any component of the formulation. concurrent active serious or uncontrolled infection breast-feeding

Hepatic impairment: manufacturer advises caution in impairment—consider dose reduction; avoid in patients with raised bilirubin

Renal impairment: avoid monotherapy if creatinine clearance less than 30 ml/minute; avoid combination regimens if creatinine clearance less than 60 ml/minute.

Pregnancy: effective contraception recommended during and for at least 3 months after treatment in women and during and for at least 5 months after treatment in men.

Breast-feeding: manufacturer advises avoid breast- feeding: during and for 3 months after treatment.

Side Effects: MOST COMMON: Central nervous system: Fatigue, fever, headache, paresthesia Dermatologic: Palmar-Plantar erythrodysesthesia, alopecia, skin rash Endocrine & metabolic: Hypokalemia, hypophosphatemia.

Gastrointestinal: Nausea, vomiting, anorexia, constipation, diarrhea, abdominal pain, stomatitis, weight gain, dyspepsia, mucosal inflammation.

Hematologic: Anemia, leukopenia, neutropenia, thrombocytopenia, decreased neutrophils.

Hepatic: Increased ALT, increased AST, increased alkaline phosphatase, hyperbilirubinemia.

Local: Phlebitis, injection/catheter site reactions Neuromuscular & skeletal: Increased CPK, weakness, arthralgia. Renal: Increased serum creatinine Respiratory: Dyspnea, cough. LESS COMMON: Cardiovascular: Peripheral edema, palpitation, edema, syncope, chest pain, left ventricular dysfunction. Central nervous system: Insomnia, dizziness. Dermatologic: Hyperpigmentation. Endocrine & metabolic: Dehydration. Gastrointestinal: Decreased appetite, dysgeusia Hematologic: Bleeding complications, febrile neutropenia, decreased white blood cell count, decreased hemoglobin, decreased platelet count, bone marrow failure, granulocytopenia, pancytopenia, neutropenic infection. Hepatic: Increased serum transaminases, hepatotoxicity. Hypersensitivity: Hypersensitivity. Local: Catheter site pain, catheter site erythema, catheter site inflammation. Neuromuscular & skeletal: Myalgia, peripheral neuropathy, musculoskeletal pain. Renal: Renal failure. Respiratory: Pulmonary embolism, pulmonary edema. Miscellaneous: Neutropenic sepsis. RARE (Limited to important or life-threatening): Extravasation (with tissue necrosis, requiring debridement), prolonged QT interval on ECG, rhabdomyolysis.

Dose:

Note: Prior to each treatment cycle, ANC should be ≥1500/mm3, platelets ≥100, 000/mm3, hemoglobin ≥9g/dL, bilirubin ≤ULN; alkaline phosphatase (nonosseous origin), ALT and AST ≤2.5 times ULN; albumin ≥25 g/L; creatinine clearance ≥30 ml/minute (single-agent therapy), serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 ml/minute (combination therapy with doxorubicin liposomal); and CPK ≤2.5 times ULN. Premedicate with dexamethasone IV 20 mg 30 minutes prior to infusion (for hepatoprotective and antiemetic effects); additional antiemetics may be administered.