Yondelis 0.25 mg powder for concentrate for solution for infusion/Yondelis 1 mg powder for concentrate for solution for infusion 

Yondelis must be administered under the supervision of a physician experienced in the use of chemotherapy. Its use should be confined to qualified oncologists or other health professionals specialised in the administration of cytotoxic agents.

Posology

For the treatment of soft tissue sarcoma, 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.

For the treatment of ovarian cancer Yondelis is administered every three weeks as a 3-hour infusion at a dose of 1.1 mg/m², immediately after PLD 30 mg/m². To minimize the risk of PLD infusion reactions, the initial dose is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent PLD infusions may be administered over a 1-hour period (see also PLD Summary of Product Characteristics [SmPC] for specific administration advice).

All patients must receive corticosteroids e.g. 20 mg of dexamethasone intravenously 30 minutes prior to PLD (in combination therapy) or Yondelis (in monotherapy); not only as anti-emetic prophylaxis, but also because it appears to provide hepatoprotective effects. Additional anti-emetics may be administered as needed.

The following criteria are required to allow treatment with Yondelis:

- 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 gamma glutamyl transpeptidase (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 (monotherapy), serum creatinine ≤ 1.5 mg/dl (≤ 132.6 μmol/l) or creatinine clearance ≥ 60 ml/min (combination therapy)

- Creatine phosphokinase (CPK) ≤ 2.5 x ULN

- Haemoglobin ≥ 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 haematological 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.

The same dose should be given for all cycles provided that no grade 3-4 toxicities are seen and that the patient fulfils the re-treatment criteria.

Dose adjustments during treatment

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, according to table 1 below, for subsequent cycles:

- Neutropenia < 500/mm³ lasting for more than 5 days or associated with fever or infection

- Thrombocytopenia < 25,000/mm³

- Increase of bilirubin > ULN and/or alkaline phosphatase > 2.5 x ULN

- Increase of aminotransferases (AST or ALT) > 2.5 x ULN (monotherapy) or > 5 x ULN (combination therapy), which has not recovered by day 21

- Any other grade 3 or 4 adverse reactions (such as nausea, vomiting, fatigue)

Once a dose has been reduced because of toxicity, dose escalation in the subsequent cycles is not recommended. If any of these toxicities reappear in subsequent cycles in a patient exhibiting clinical benefit, the dose may be further reduced (see below). Colony stimulating factors can be administered for haematologic toxicity according to local standard practice.

Table 1 Dose modification table for Yondelis (as single agent for soft tissue sarcoma (STS) or in combination for ovarian cancer) and PLD

See the PLD SmPC for more detailed information on PLD dose adjustments.

In the event that further