The Association Between Body Composition and Toxicities From the Combination of Doxil and Trabectedin in Patients With Advanced Relapsed Ovarian Cancer

Appl Physiol Nutr Metab. 2014 Jun;39(6):693-8. doi: 10.1139/apnm-2013-0403. Epub 2014 Jan 23.

Abstract

Emerging research suggests that body composition can predict toxicity of certain chemotherapeutic agents. We used data from a clinical study to investigate associations between body composition and combined DOXIL (pegylated liposomal doxorubicin; PLD) and trabectedin (Yondelis) treatment, an effective treatment for ovarian cancer that shows high interpatient variation in toxicity profile. Patients (n = 74) participating in a phase III randomized trial of relapsed advanced ovarian cancer receiving PLD (30 mg/m(2)) and trabectedin (1.1 mg/m(2)) were included. Muscle tissue was measured by analysis of computerized tomography images, and an extrapolation of muscle and adipose tissue to lean body mass (LBM) and fat mass (FM) were employed. Toxicity profile after cycle 1 was used and graded according to the National Cancer Institute Common Toxicity Criteria (version 3). Patients presented with a wide range of body composition. In overweight and obese patients (body mass index (BMI) ≥ 25 kg/m(2), n = 48) toxicity was more prevalent in those with lower BMI (p = 0.028) and a lower FM (n = 43, p = 0.034). Although LBM alone was not predictive of toxicity, a lower FM/LBM ratio was the most powerful variable associated with toxicity (p = 0.006). A different pattern emerged among normal weight patients (n = 26) where toxicity was rare among patients with smaller BMI (<21 kg/m(2)). A clear association between both FM and LBM (primarily driven by FM) in explaining PLD plus trabectedin toxicity emerged, but only in individuals with excess body weight, with a lower ratio predicting higher exposure and risk for toxicity.

Keywords: DOXIL; Doxil; body composition; cancer ovarien; chemotherapy; chimiothérapie; composition corporelle; computerized tomography; ovarian cancer; tomographie assistée par ordinateur; toxicity; toxicité; trabectedin; trabectédine.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / adverse effects*
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Body Composition*
  • Dexamethasone / adverse effects
  • Dioxoles / adverse effects*
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Staging
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Polyethylene Glycols / adverse effects
  • Tetrahydroisoquinolines / adverse effects*
  • Tomography, X-Ray Computed
  • Trabectedin
  • Treatment Outcome

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Tetrahydroisoquinolines
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Dexamethasone
  • Doxorubicin
  • Trabectedin