A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin

Federica Grosso, Maurizio D'Incalci, Mirela Cartoafa, Antonio Nieto, Carlos Fernández-Teruel, Vicente Alfaro, Pilar Lardelli, Elena Roy, Javier Gómez, Carmen Kahatt, Arturo Soto-Matos, Ian Judson

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: This analysis determined the incidence of serious rhabdomyolysis events reported during trabectedin treatment since the first phase I clinical trial in April 1996 up to September 2010. Methods: Search was done in the Yondelis® Pharmacovigilance and Clinical Trials databases using a list of terms according to the Medical Dictionary for Regulatory Activities (MedDRA, v. 13.1), followed by a medical review of all cases retrieved. Total estimated sample was 10,841 patients: 2,789 from clinical trials; 3,926 from compassionate use programs; and 4,126 treated in the marketplace. Two groups were identified: (1) rhabdomyolysis and (2) clinically relevant creatine phosphokinase (CPK) increases without acute renal failure (ARF). Descriptive analysis included demographic, clinical/laboratory data, and contributing/confounding factors. Potential predictive factors were evaluated by multivariate stepwise logistic regression analysis. Possible changes of pharmacokinetics (PK) in patients with rhabdomyolysis were explored using a population PK model. Results: The global incidence of rhabdomyolysis was 0.7 %, and most cases occurred in Cycle 2 of treatment. The incidence of fatal cases was 0.3 %. None of the variables evaluated to detect potential risk factors of rhabdomyolysis were predictive. Additionally, CPK increases (without ARF) were detected in 0.4 % of patients as an incidental finding with good prognosis. Conclusions: Rhabdomyolysis is an uncommon event during trabectedin treatment. Multivariate analyses did not show any potential factor that could be predictive or represent a significantly higher risk of developing rhabdomyolysis. Nevertheless, close patient monitoring and adherence to drug administration guidelines may help to limit the incidence of this event.

Original languageEnglish
Pages (from-to)1557-1565
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume69
Issue number6
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Creatine phosphokinase
  • Rhabdomyolysis
  • Trabectedin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

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