Investigational New Drugs

, Volume 31, Issue 5, pp 1236–1243 | Cite as

Phase I clinical and pharmacokinetic study of trabectedin and cisplatin given every three weeks in patients with advanced solid tumors

  • Cristiana SessaEmail author
  • Gianluca Del Conte
  • Alexandre Christinat
  • Sara Cresta
  • Antonella Perotti
  • Elisa Gallerani
  • Pilar Lardelli
  • Carmen Kahatt
  • Vicente Alfaro
  • Jorge L. Iglesias
  • Carlos Fernández-Teruel
  • Luca Gianni


The aim of this phase I study was to identify a feasible dose and schedule for the combination of cisplatin and trabectedin. The regimen evaluated consisted of cisplatin at a fixed dose of 75 mg/m2 1-hour intravenous (i.v.) infusion followed by escalating doses of trabectedin 3-hour i.v. infusion, both administered on day 1 every 3 weeks (q3wks). Two dose-limiting toxicities (DLTs), grade 4 neutropenia longer than 7 days duration and grade 3 vomiting despite standard antiemetic therapy, occurred at the starting dose of trabectedin (0.75 mg/m2). The immediately lower dose (trabectedin 0.60 mg/m2) was evaluated in a total of 8 patients; no DLTs occurred and this was declared the recommended dose (RD). The safety profile of the combination at this dose and schedule was consistent with the known side effects of each agent alone: nausea, fatigue, transient transaminase elevations and neutropenia. No new or unexpected adverse reactions were observed. Two partial responses were reported at the RD in patients with pretreated ovarian cancer. Comparison with population pharmacokinetic data suggests a PK interaction between trabectedin and cisplatin leading to increased plasma exposure of trabectedin in the first 48 h, lower platinum clearance and longer half-life. In conclusion, although the trabectedin dose achieved with this combination was low (50 % of single-agent when given q3wks), this day 1 q3wks trabectedin plus cisplatin combination showed a feasible administration, a tolerable safety profile and some antitumor activity.


Phase I Trabectedin Cisplatin Antitumor Cytotoxic Dose-limiting toxicities 



This study was supported by PharmaMar, S.A., and preliminary results were presented at the American Society of Clinical Oncology (ASCO) 47th Annual Meeting, Jun 3–7, 2011. Chicago, Illinois: Phase I Dose-Finding Study of Trabectedin in combination with Cisplatin in Patients with Advanced Solid Tumors. Sessa, C.; Gallerani, E.; Del Conte, G.; Christinat, A.; Perotti, A.; Lardelli, P.; Kahatt, C.; Flórez, A.; Fernández, C.; Gianni, L. J Clin Oncol 29:2011 (suppl: abstract 2517).

Conflict of interest

Pilar Lardelli, Carmen Kahatt, Vicente Alfaro, Jorge L. Iglesias, and Carlos Fernández-Teruel are employees in PharmaMar.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Cristiana Sessa
    • 1
    • 2
    Email author
  • Gianluca Del Conte
    • 2
  • Alexandre Christinat
    • 1
  • Sara Cresta
    • 3
  • Antonella Perotti
    • 2
  • Elisa Gallerani
    • 1
  • Pilar Lardelli
    • 4
  • Carmen Kahatt
    • 4
  • Vicente Alfaro
    • 4
  • Jorge L. Iglesias
    • 4
  • Carlos Fernández-Teruel
    • 4
  • Luca Gianni
    • 2
  1. 1.Istituto Oncologico della Svizzera (IOSI)Ospedale San GiovanniBellinzonaSwitzerland
  2. 2.Unit of New Drugs and Innovative Therapies, Department of Medical OncologySan Raffaele Hospital, IRCCSMilanItaly
  3. 3.Istituto Nazionale dei TumoriMilanoItaly
  4. 4.PharmaMar, Clinical R&DMadridSpain

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