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Investigational New Drugs

, Volume 30, Issue 3, pp 1193–1202 | Cite as

A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials

  • Axel Le CesneEmail author
  • Alejandro Yovine
  • Jean-Yves Blay
  • Suzette Delaloge
  • Robert G. Maki
  • Jean-Louis Misset
  • Pilar Frontelo
  • Antonio Nieto
  • Juhui James Jiao
  • George D. Demetri
PHASE II STUDIES

Summary

Purpose To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. Methods This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n = 570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n = 258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n = 304/1,198 cycles). Results The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1–59). Nausea, fatigue and vomiting were the most common trabectedin-related adverse events, reported in ≥20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients. Conclusion Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time.

Keywords

Trabectedin Cancer Safety Phase II Single-agent Yondelis ET-743 

Notes

Acknowledgements

The authors wish to thank Claudia Lebedinsky, Vicente Alfaro and Javier Gómez for their help during the preparation of this manuscript.

This study was supported by funding from PharmaMar. Preliminary results of this study were presented as a poster at the 2009 Annual Connective Tissue Oncology Society (CTOS) Meeting and as a publication-only abstract at the 2009 ASCO Annual Meeting.

Authors’ disclosures of potential conflicts of interest

A Le Cesne and JY Blay have received research support and honoraria from PharmaMar and Jonhson & Johnson. S Delaloge has received honoraria from PharmaMar. GD Demetri has served as scientific consultant for both PharmaMar and Johnson & Johnson, and Dana-Farber/Harvard has received research support for the conduct of clinical trials from both PharmaMar and Johnson & Johnson. RG Maki has received research support from PharmaMar. JL Misset has received research support and honoraria from PharmaMar. A Yovine, P Frontelo and A Nieto are present or former employees in PharmaMar and are stock owners. JJ Jiao is employee in Johnson & Johnson.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Axel Le Cesne
    • 1
    Email author
  • Alejandro Yovine
    • 2
  • Jean-Yves Blay
    • 3
  • Suzette Delaloge
    • 1
  • Robert G. Maki
    • 4
  • Jean-Louis Misset
    • 2
  • Pilar Frontelo
    • 5
  • Antonio Nieto
    • 5
  • Juhui James Jiao
    • 6
  • George D. Demetri
    • 7
  1. 1.Department of MedicineInstitut Gustave RoussyVillejuif CedexFrance
  2. 2.Hôpital St LouisParisFrance
  3. 3.Centre Léon BérardLyonFrance
  4. 4.Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.PharmaMar Clinical R&D, Colmenar ViejoMadridSpain
  6. 6.Johnson & Johnson Pharmaceutical Research & Development, L.L.C.RaritanUSA
  7. 7.Ludwig Center at Dana-Farber Cancer Institute and Harvard Medical SchoolBostonUSA

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