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 journalArticle

18 Citations (Scopus)

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

Fingerprint

trabectedin
Rhabdomyolysis
Pharmacokinetics
Creatine Kinase
Safety
Clinical laboratories
Patient monitoring
Glossaries
Regression analysis
Incidence
Logistics
Acute Kidney Injury
Medical Dictionaries
Compassionate Use Trials
Clinical Trials
Pharmacovigilance
Clinical Trials, Phase I
Incidental Findings
Pharmaceutical Preparations
Physiologic Monitoring

Keywords

  • Creatine phosphokinase
  • Rhabdomyolysis
  • Trabectedin

ASJC Scopus subject areas

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

Cite this

A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin. / Grosso, Federica; D'Incalci, Maurizio; Cartoafa, Mirela; Nieto, Antonio; Fernández-Teruel, Carlos; Alfaro, Vicente; Lardelli, Pilar; Roy, Elena; Gómez, Javier; Kahatt, Carmen; Soto-Matos, Arturo; Judson, Ian.

In: Cancer Chemotherapy and Pharmacology, Vol. 69, No. 6, 06.2012, p. 1557-1565.

Research output: Contribution to journalArticle

Grosso, F, D'Incalci, M, Cartoafa, M, Nieto, A, Fernández-Teruel, C, Alfaro, V, Lardelli, P, Roy, E, Gómez, J, Kahatt, C, Soto-Matos, A & Judson, I 2012, 'A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin', Cancer Chemotherapy and Pharmacology, vol. 69, no. 6, pp. 1557-1565. https://doi.org/10.1007/s00280-012-1864-4
Grosso, Federica ; D'Incalci, Maurizio ; Cartoafa, Mirela ; Nieto, Antonio ; Fernández-Teruel, Carlos ; Alfaro, Vicente ; Lardelli, Pilar ; Roy, Elena ; Gómez, Javier ; Kahatt, Carmen ; Soto-Matos, Arturo ; Judson, Ian. / A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin. In: Cancer Chemotherapy and Pharmacology. 2012 ; Vol. 69, No. 6. pp. 1557-1565.
@article{92891ed643b84b7eb1368db1d1ab6562,
title = "A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin",
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{\circledR} 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.",
keywords = "Creatine phosphokinase, Rhabdomyolysis, Trabectedin",
author = "Federica Grosso and Maurizio D'Incalci and Mirela Cartoafa and Antonio Nieto and Carlos Fern{\'a}ndez-Teruel and Vicente Alfaro and Pilar Lardelli and Elena Roy and Javier G{\'o}mez and Carmen Kahatt and Arturo Soto-Matos and Ian Judson",
year = "2012",
month = "6",
doi = "10.1007/s00280-012-1864-4",
language = "English",
volume = "69",
pages = "1557--1565",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - A comprehensive safety analysis confirms rhabdomyolysis as an uncommon adverse reaction in patients treated with trabectedin

AU - Grosso, Federica

AU - D'Incalci, Maurizio

AU - Cartoafa, Mirela

AU - Nieto, Antonio

AU - Fernández-Teruel, Carlos

AU - Alfaro, Vicente

AU - Lardelli, Pilar

AU - Roy, Elena

AU - Gómez, Javier

AU - Kahatt, Carmen

AU - Soto-Matos, Arturo

AU - Judson, Ian

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

KW - Creatine phosphokinase

KW - Rhabdomyolysis

KW - Trabectedin

UR - http://www.scopus.com/inward/record.url?scp=84863793434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863793434&partnerID=8YFLogxK

U2 - 10.1007/s00280-012-1864-4

DO - 10.1007/s00280-012-1864-4

M3 - Article

C2 - 22484722

AN - SCOPUS:84863793434

VL - 69

SP - 1557

EP - 1565

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 6

ER -