Soft Tissue Sarcoma Knowledge Centre
Management
Novel Therapy - Trabectedin
Safety And Tolerability1-16
The results of the single-arm phase II studies and randomised study in pretreated patients with STS indicate that:
Trabectedin (Yondelis®- see prescription information) side effects have been found to be generally manageable when administered at the recommended dose of 1.5 mg/m2 24-hr q3wk. Toxicities are generally non-cumulative, reversible and manageable.
The main treatment-related Grade 3/4 toxicities are haematological toxicities (neutropenia and thrombocytopenia) and transient elevation in plasma transaminase liver enzymes (AST, ALT). Grade 3/4 nausea and vomiting were also observed but in less than 10%of patients, while Grade 3/4 fatigue was observed in 6% of patients in the randomised study. However, no patients discontinued treatment because of these toxicities.
Yondelis® is not associated with cardiotoxicity, nervous system disorders, or stomatitis. Skin and subcutaneous tissue disorders, like alopecia was rare and generally mild. Premedication with dexamethasone reduces the incidence of nausea and vomiting associated with Yondelis® and is thus mandatory.
Yondelis® side effects have been found to be generally manageable in elderly patients. Yondelis® should not be used in patients with severe renal impairment or severe liver dysfunction. Monitoring is recommended for patients with clinically relevant liver disease.
Summary of Product Characteristics (SmPC)
Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.gov.uk. Adverse events should also be reported to Pharma Mar (contact details below).
Adverse Events Reporting
Pharmacovigilance Department
- Fax: +34 91 846 6004
- Tel: +34 91 846 6055
- e-mail: phv@pharmamar.com
References:
1. Garcia-Carbonero R, Supko JG et al. (2004) “Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.” J Clin Oncol 22(8): 1480–90
2. Le Cesne A, Blay JY et al. (2005) “Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial.” J Clin Oncol 23(3): 576–84.9
3. Yovine A, Riofrio M et al. (2004) “Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients.” J Clin Oncol 22(5): 890–99.
4. Chawla S, Casali PG et al. (2007) “Clinical tolerability of trabectedin administered by two different schedules (weekly for 3 of 4weeks vs. q3weeks) in patients with locally advanced/metastatic liposarcoma or leiomyosarcoma (L-sarcoma) progressing despite prior treatment with at least anthracycline and ifosfamide.” Eur J Cancer 5(4): Abstract 7517.
5. Morgan JA, Le Cesne A et al. (2007) “Randomized phase II study of trabectedin in patients with liposarcoma and leiomyosarcoma after failure of prior anthracycline and ifosfamide.” J Clin Oncol 25(18S): Abstract 10060.
6. Brain EG. (2002) “Safety and efficacy of ET-743: the French experience.” Anticancer Drugs 13(Suppl 1): S11–14.
7. Cvetkovic RS, Figgitt DP et al. (2002) “Et-743.” Drugs 62(8): 1185-92.
8. Demetri GD. (2002b) “ET-743: the US experience in sarcomas of soft tissues.” Anticancer Drugs 13(Suppl 1): S7–9.
9. Puchalski TA, Ryan DP et al. (2002) “Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity.” Cancer Chemother Pharmacol 50(4): 309–19.
10. Lopez-Martin JA, Nieto A et al. (2002) “Safety profile of ecteinascidin-743 in phase II clinical trials (CT) in adult patients with solid tumors.” Proc Am Soc Clin Oncol 21: Abstract 382.
11. Le Cesne A, Antoine E et al. (1995) “High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.” J Clin Oncol 13(7): 1600–8.
12. Nielsen OS, Judson I et al. (2000) “Effect of high-dose ifosfamide in advanced soft tissue sarcomas. Amulticentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.” Eur J Cancer 36(1): 61–67.
13. Judson I, Radford JA et al. (2001) “Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced ormetastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.” Eur J Cancer 37(7): 870–77.
14. Verweij J, Lee SM et al. (2000) “Randomized phase II study of docetaxel versus doxorubicin in first- and second-line chemotherapy for locally advanced or metastatic soft tissue sarcomas in adults: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.” J Clin Oncol 18(10): 2081–6.
15. Yondelis®. (2007) Summary of product characteristics. PharmaMar: Madrid, Spain
16. Salazar R, Pardo B et al. (2006) “Phase I clinical and pharmacological trial of trabectedin in 3 hour infusion every 3 weeks in patients with advanced cancer and hepatic function disorder.” J Clin Oncol 24(18S): Abstract 2080.