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Management

Novel Therapy - Trabectedin

Efficacy1-10

The efficacy of Trabectedin (Yondelis®- see prescription information) monotherapy in patients with STS has been demonstrated in the results of a randomised study involving 270 patients and is supported by the results of three previously conducted single-armphase II studies. The results of these studies indicate that:

Yondelis® is effective when administered at a dose of 1.5 mg/m2 24-hr q3wk (i.e. the recommended regime). This regime is superior to a weekly regime of 0.58 mg/m2 administered as a 3-hour infusion. With Yondelis® at the recommended regime, the median TTP was 3.7 months, with a significant 27% reduction in the risk of progression relative to the 3-hr qwk schedule (p=0.0302).

With Yondelis® at the recommended regime the median PFS was 3.3 months in the randomised study and PFS rates at 3 months and 6 months were 51.5% and 35.5%. Similar PFS rates were also obtained in the EORTC study (3 months, 52%; 6 months, 29%). The 6-month PFS rates reported for Yondelis® in both studies seem to be favourable versus the 14% 6-month PFS rates reported by Van Glabbeke et al for active regimes in pre-treated patients with STS.

A clinical benefit rate (CR+PR+SD ?24 weeks) of 38.9% was achieved with the recommended regime in the randomised study.  Yondelis®, at the recommended regime, was associated with a median OS of 13.8 months and a 1-year OS of 60.6%. These data seem to be favourable versus those reported in patients with STS having progressed after second-line ifosfamide and for second-line treatment with dacarbazine or etoposide, and versus survival data for first-line anthracycline-based chemotherapy in patients with advanced/metastatic STS.

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

References:
1. Van Glabbeke M, Verweij J et al. (2002) “Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas.” Eur J Cancer 38(4): 543–49.
2. Blay JY, van GlabbekeMet al. (2003) ”Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy.” Eur J Cancer 39: 64–69.
3. Garcia-Carbonero R, Supko JG et al. (2004) “Phase II and pharmacokinetic study of ecteinascidin 743 in patientswith progressive sarcomas of soft tissues refractory to chemotherapy.” J Clin Oncol 22(8): 1480–90.
4. 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. 
5. Therasse P, Le Cesne A et al. (2005) “RECIST vs.WHO: prospective comparison of response criteria in an EORTC phase II clinical trial investigating ET-743 in advanced soft tissue sarcoma.” Eur J Cancer 41(10): 1426–30.
6. Le Cesne A, Judson I et al. (2000) “Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: a trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group.” J Clin Oncol 18(14): 2676–84.
7. Le Cesne A, Demetri G et al. (2003) “Impact of Yondelis™ (trabectedin, ET-743) in the natural history of patients (pts) with pretreated advanced soft tissue sarcomas (PASTS): Long term follow-up results.” Clin Cancer Res 9 (Suppl): Abstract 31.
8. 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.
9. Le Cesne A, von Mehren M et al. (2007) “Assessing the clinical impact of trabectedin in patients with leiomyosarcomas or liposarcomas (L-sarcomas) progressing despite prior conventional chemotherapy: clinical benefit rate, growth modulation index and tumor variation as parameters of treatment effect in a randomised international trial of two trabectedin dosing regimens.” Eur J Cancer 5(4): Abstract 7512.
10. 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.

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