Effect of renin-angiotensin system inhibitors on pemetrexed plus platinum-induced hematological toxicities: A multicenter retrospective study using three propensity score analyses

T. Arami, H. Kawazoe, R. Uozumi, H. Hashimoto, S. Egami, N. Sakiyama, Y. Ohe, Hideo Nakada, T. Aomori, S. Ikemura, H. Yasuda, I. Kawada, K. Fukunaga, K. Soejima, M. Yamaguchi, T. Nakamura

Research output: Contribution to journalArticlepeer-review

Abstract

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32; p = 0.536). Additionally, sensitivity analyses using PS-adjusted and IPTW methods demonstrated similar results (OR, 0.63; 95% CI, 0.19-2.15; p = 0.463 and OR, 0.37; 95% CI, 0.11-1.29; p = 0.117, respectively). These findings suggest that RASIs might prevent pemetrexed plus platinum-induced hematological toxicities.

Original languageEnglish
Pages (from-to)266-271
Number of pages6
JournalPharmazie
Volume76
Issue number6
DOIs
Publication statusPublished - 2021 Jun

ASJC Scopus subject areas

  • Pharmaceutical Science

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