Effects of proton pump inhibitors on severe haematotoxicity induced after first course of pemetrexed/carboplatin combination chemotherapy. (15th December 2018)

• Record Type: Journal Article
• Authors: Araki, Ryosuke; Keira, Takayuki; Masuda, Yutaka; Tanaka, Tsuneaki; Yamada, Hideki; Hamamoto, Tomoyuki
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 44:Number 2(2019)
• Page Start: 276
• Page End: 284
• Publication Date: 2018-12-15
• Subjects: carboplatin -- concomitant drug -- haematotoxicity -- pemetrexed -- proton pump inhibitor -- relative dose intensity; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12788
• Languages: English
• ISSNs: 0269-4727

Abstract

Summary: What is Known and Objective: Pemetrexed/carboplatin combination chemotherapy has shown efficacy as a first‐line treatment for advanced non‐small‐cell lung cancer. However, severe haematotoxicity is often observed during this combination chemotherapy. Some studies have suggested that concomitant drugs may be the risk factors for severe adverse events. However, those studies identified the predictive risk factors without paying attention to the relative dose intensities (RDIs) of the anticancer drugs. The objective of this study was to clarify the effects of concomitant drugs on the severe haematotoxicity induced by pemetrexed/carboplatin combination chemotherapy using multiple logistic regression analysis incorporating RDIs of the anticancer drugs. Methods: We retrospectively reviewed the records of 61 patients who had received first‐line treatment with this combination chemotherapy at Yamato Municipal Hospital between April 2011 and May 2017. Severe haematotoxicity was defined as grade 3 or 4 according to the Common Terminology Criteria for Adverse Events, version 4.0. To clarify the influence of concomitant drugs on haematotoxicity, we performed multiple logistic regression analysis. Results: Among the 61 patients, 18 (29.5%) developed grade 3 or 4 haematotoxicity. Multiple logistic regression analysis showed that body weight <54.5 kg [odds ratio: 5.21, 95% confidence interval (CI): 1.17‐23.08, P = 0.030], haemoglobin <12.0 g/dL [odds ratio: 7.13, 95% CI: 1.54‐33.11, P = 0.012], and coadministration of proton pump inhibitors (PPIs) [odds ratio: 5.34, 95% CI: 1.06‐26.94, P = 0.042] were significantly associated with severe haematotoxicity in patients receiving pemetrexed/carboplatin combination chemotherapy after adjustment using non‐steroidal anti‐inflammatory drugs and RDIs of the anticancer drugs. What is New and Conclusion: Multiple logistic regression analysis incorporating RDIs of the anticancer drugs revealed that low baseline body weight, low baseline haemoglobin level, and coadministration of PPIs were the independent risk factors for predicting severe haematotoxicity induced by pemetrexed/carboplatin combination chemotherapy.