Carboplatin-induced hematotoxicity among patients with non-small cell lung cancer: Analysis on clinical adverse events and drug-gene interactions

// Yi-ju Cheng 1,2,* , Ran Wu 3,* , Ming-liang Cheng 4 , Juan Du 1,2 , Xi-wei Hu 1 , Lei Yu 5 , Xue-ke Zhao 4 , Yu-mei Yao 4 , Qi-zhong Long 1,2 , Li-li Zhu 4 , Juan-juan Zhu 4 , Ni-wen Huang 1 , Hua-juan Liu 4 , Ya-xin Hu 4 and Fang Wan 1 1 Department of Respiratory Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China 2 Department of Respiratory Medicine, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang, Guizhou, China 3 Department of Dermatology, The First Affiliated Hospital of Guiyang college of Traditional Chinese Medicine, Baoshanbei Guiyang, Guizhou, China 4 Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China 5 Prenatal Diagnostic Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China * These authors have contributed equally to this work Correspondence to: Ming-liang Cheng, email: // Lei Yu, email: // Keywords : carboplatin; anemia; neutropenia; thrombocytopenia; FDA adverse event reporting system Received : June 14, 2016 Accepted : October 21, 2016 Published : October 27, 2016 Abstract In order to clarify the risk of hematotoxicity of carboplatin, we inspected 19901 case reports of non-small cell lung cancer patients that were submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These comprised 3907 cases which were treated with carboplatin and 15994 cases which were treated with other therapies in the absence of carboplatin. By comparison, carboplatin cases were significantly more likely to report anemia (OR = 2.27, 95% CI 1.85-2.78, P = 5.04×10 -15 ), neutropenia (OR = 2.27, 95% CI 1.76-2.92, P = 2.39×10 -10 ), and thrombocytopenia (OR = 2.38, 95% CI 1.84-3.08, P = 5.60×10 -11 ). We further explored published evidences and found 205 human genes interacting with carboplatin. Functional analysis corroborated that these genes were significantly enriched in the biochemical pathway of hematopoietic cell lineage (adjusted P = 6.02×10 -11 ). This indicated that carboplatin could profoundly affect the development of blood cells. Given the early awareness of the hematologic risks, great caution should be exercised in prescribing carboplatin to non-small cell lung cancer patients. And functional enrichment analysis on carboplatin-related genes warranted subsequent research with regard to the underlying toxicological mechanisms.