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

• Published in: Oncotarget Vol. 8; no. 19; pp. 32228 - 32236
• Main Authors: Cheng, Yi-Ju, Wu, Ran, Cheng, Ming-Liang, Du, Juan, Hu, Xi-Wei, Yu, Lei, Zhao, Xue-Ke, Yao, Yu-Mei, Long, Qi-Zhong, Zhu, Li-Li, Zhu, Juan-Juan, Huang, Ni-Wen, Liu, Hua-Juan, Hu, Ya-Xin, Wan, Fang
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 09-05-2017
• Subjects: Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Carboplatin - adverse effects; Carboplatin - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Clinical Research Paper; Data Interpretation, Statistical; Databases, Factual; Hematopoiesis - drug effects; Hematopoiesis - genetics; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Odds Ratio; Pharmacogenetics - methods; Pharmacogenomic Variants; Treatment Outcome; neutropenia; FDA adverse event reporting system; thrombocytopenia; carboplatin; anemia
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.12951

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.