Low Skeletal Muscle Density is Predictive for Febrile Neutropenia in Patients Treated By Doxorubicin/Trabectedin/Pegfilgrastim Combination As a First-Line Treatment of Advanced or Metastatic Leiomyosarcoma (Lms) (Lms02 Study)

Abstract

ABSTRACT Background: Studies have shown that skeletal muscle mass (SMM) and skeletal muscle densities (SMD) are associated to chemotherapy toxicity. In 110 patients treated with a combination of doxorubicin (doxo) and trabectedin (trab), neutropenia and febrile neutropenia are still observed despite the use of granulocyte colony stimulating factor (G-CSF) (ASCO 2013; abstract 10505). Our aim was to analyze whether SMM or SMD are predictive of febrile neutropenia Methods: SMM and SMD were assessed with computed tomography (CT) imaging before treatment by measuring cross-sectional areas of the tissues for SMM and the mean muscle Hounsfield Units (HU) for SMD. SMD assessed by this method reflects fatty muscle infiltration with lower mean HU reflecting lower density, and more fatty infiltration. Toxicity profile was collected for all cycles. Therefore severe toxicity is defined as any grade 3 or 4 toxicity. The cut-off level which predicts the occurrence of toxicity most accurately was deduced from the receiver operating characteristic curve (for SMD the value is: 37.1 HU). Pts received doxo 60 mg/m2 followed by trab 1.1 mg/m2 IV in 3-h at day 1, and pegfilgrastim 6 mg on day 2 every 21 days for a maximum of 6 cycles Results: 55 pts were included (46 females and 9 males), with median age of 58 years, 27 pts with uterine LMS and 28 with soft tissue LMS were analyzed. Only 2 pts had an ECOG PS score >1. Pts received a total of 285 cycles with a median of 6 cycles per pt. Pts with a low density (SMD 37.1 (6/36; 17%) (p=0.05). No association between toxicity and SMM was found. Conclusions: Despite the use of GCSF, febrile neutropenia is observed in pts treated with doxo+trab. In this pilot study including a few pts, muscle density has been found to be associated with a high probability of febrile neutropenia. These interesting results need to be confirmed. They might highlight the concept of frailty i.e. a group of non-oncologic parameters associated with a higher susceptibility to events Disclosure: S. Antoun: Advisory board for Baxter nutrition; P. Pautier: Expert board for PHARMAR. All other authors have declared no conflicts of interest.