Abstract 5579: Medication exposures and subsequent development of Ewing sarcoma: a review of FDA adverse event reports
Authors: Cope Judith U. , Reaman Gregory H. , Tonning Joseph M. 
Published: August 2015

BACKGROUND: Ewing sarcoma family of tumors (ESFT) are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT.

METHODS: A query of the FDA Adverse Event Reporting System (FAERS) was conducted from January 1, 1998 through December 31, 2013 for all case reports of ESFT. Report narratives were individually reviewed for patient characteristics, underlying conditions, and drug exposures.

RESULTS: Over the past 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drug use. Reported drugs and biologics associated with these cases included immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies.

CONCLUSIONS: This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While we found no clear causative association between ESFT and prior use of a single product or drug class, many associated drugs were used to treat immune-related disease, and growth or hormonal disturbances. Further studies are needed to better understand possible immune or neuroendocrine abnormalities that may predispose to the later development of ESFT.

Table: Summary of FAERS reports of medication use prior to Ewing Sarcoma Family of Tumor (ESFT) diagnosis, 1997-2013Total = 25; 13 US, 12 foreign; 16 females, 9 malesAges 4-68 yrs (median age 24 years; mean 30 years)Known latency for 20 patients: 3 mos - 12 years (median 2 yrs; mean 3.2 yrs); 5 unknownDrug use # cases pt age (yr) latencyImmunosuppressive* 12 5-68 mean 4.2 yrsGrowth hormone (GH) 2* 11, 16 5 yrs; 18 mosEstrogen/progestin 2 24, 47 10 mos, 2.5 yrsCNS depressant 2 34, 42 22 mos;unknownAtypical antipsychotic 1 17 no infoAntiepileptic 1 8 8 yrsAntipsychotic and AED 1 19 3 mosADHD 1 8 no infoIsotretinoin 1 20 10 mosStatin for hyperlipidemia 1 9 &gt;2 yrsrPTH** 1 49 1 year*1 patient with Crohns also received GH**rPTH, recombinant parathyroid hormone

Underlying conditions

12 Immune-related: 3 Crohns disease, 3 multiple sclerosis, 1 renal transplant, 1 rheumatoid arthritis, 1 nephrotic syndrome, 1 ankylosing spondylitis, 1 psoriasis vulgaris, 1 chronic hepatitis B

5 Endocrine: 2 Growth disorders, 1 menopause, 1 osteoporosis, 1 birth control (patient morbidly obese but no underlying condition reported)

3 Neurologic: 1 each of narcolepsy, seizure disorder, fibromyalgia with sciatica/neuropathic pain

3 Psychiatric: 1 each of unspecified depression, psychoses, ADHD

2 Other: 1 each of familial hypercholesterolemia, acne

Citation Format: Judith U. Cope, Gregory H. Reaman, Joseph M. Tonning. Medication exposures and subsequent development of Ewing sarcoma: a review of FDA adverse event reports. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5579. doi:10.1158/1538-7445.AM2015-5579