491P - Body composition is linked to toxicity and outcome in patients (pts) included in phase I trials

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Pharmacology
Presenter Sophie Cousin
Authors S. Cousin1, A. Hollebecque2, S. Koscielny3, A. Varga2, V. Baracos4, J. Soria2, S. Antoun5
  • 1Oncologie Generale, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 2Department Of Medicine, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 3Department Of Biostatistics And Epidemiology, Institut Gustave Roussy, 94805 - villejuif/FR
  • 4Department Of Oncology, University of alberta, Edmonton/CA
  • 5Emergency Department, Institut Gustave Roussy, 94805 - Villejuif/FR

Abstract

Background

Phase I clinical trials are dose- and toxicity–finding studies designed to identify the recommended phase II dose of new drugs. Thus, it appears crucial to distinguish toxicity directly related to the tested drug or to pts characteristics. Because previous studies have shown that sarcopenia could be linked to drug toxicity, we have evaluated the effects of body composition parameters on the toxicities incidence among phase I included pts.

Methods

We have carried out a prospective single institution study which included all pts consecutively treated from January 2011 to July 2011 in our phase I unit, irrespective of the tumor type and/or drug nature. Clinical and biological nutritional parameters were recorded. Analysis of the computerized tomography (CT) images realized within 30 days before inclusion was used to evaluate cross-sectional areas (cm2) of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and muscle tissue (MT). The 3rd lumbard vertebra (L3) was chosen as a landmark since L3 and whole-body measurements are linearly related. Images were analyzed using Slice-O-Matic software V4.3 (Tomovision). Tissue cross-sectional areas were computed. Analysis was stratified on sex. Comparisons used Chi-2 test, Kruskal-Wallis test and log rank test.

Results

The study population consisted in 64 men and 49 women. The median age was 57.3 years. Drug interruption due to toxicity (DIT) occurred in 15% of the pts. The only factor associated with DIT was low MT: 117 cm2 versus 138 cm2 (p = 0.039). Pts who did not experiment DIT were more likely to have MT > median (56% versus 15%, p = 0.007). None of the following parameters were found to be associated with DIT: weight change >5%, >10%, Albumin< 35g/l, lacticodeshydrogenase > 250 IU/l, transthyretin <0.21mg/dl, C reactive protein > 6mg/l. Additionally, VAT < median was associated with poorer overall survival (OS) (p = 0.01) and shorter progression free survival (PFS) (p = 0.02).

Conclusion

In a heterogeneous population of pts enrolled in various phase I trials, low muscle tissue was associated with the drug interruption due to toxicity. OS and PFS were linked to the VAT. Body composition is linked to toxicities risk and outcome in phase I pts.

Disclosure

All authors have declared no conflicts of interest.