Hill Jordan, Vargo Craig, Smith Michael, Streeter Jessica, Carbone David P
1 Department of Pharmacy at The James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, USA.
2 Department of Pharmacy, West Virginia University Medicine, Morgantown, USA.
J Oncol Pharm Pract. 2019 Jul;25(5):1125-1129. doi: 10.1177/1078155218780507. Epub 2018 Jun 5.
Pemetrexed has been shown to be effective in the treatment of advanced and metastatic nonsquamous nonsmall cell lung cancer. In this population, renal insufficiency is common; however, pemetrexed is not recommended in patients with a creatinine clearance (CrCl) < 45 ml/min due to increased myelosuppression reported in phase I trials. The primary objective of this study is to determine the safety of dose-reduced pemetrexed in patients with a CrCl < 45 ml/min.
This is a retrospective case series describing the incidence of grade 3 or higher toxicity in patients with CrCl < 45 ml/min treated with dose-reduced pemetrexed at The James Cancer Hospital and Solove Research Institute at The Ohio State University.
A total of eighteen patients were included. Seven (39%) patients experienced a grade ≥ 3 toxicity. Only 18% of administrations led to a grade ≥ 3 toxicity. Four (22%) patients had grade ≥ 3 hematologic toxicity; three of which were receiving concomitant platinum agents. The fourth patient had a CrCl < 30 ml/min. No patients receiving single-agent pemetrexed with a CrCl > 30 ml/min experienced grade ≥ 3 hematologic toxicity.
Dose-adjusted pemetrexed may be cautiously administered to patients with a CrCl between 30 and 45 ml/min. Extra caution is warranted in patients receiving concomitant chemotherapy with a platinum agent as well as those with a CrCl < 30 ml/min. Pemetrexed in combination with a platinum agent should not be routinely recommended for patients with a CrCl < 30 ml/min.
培美曲塞已被证明对晚期和转移性非鳞状非小细胞肺癌有效。在这一人群中，肾功能不全很常见；然而，由于I期试验报告的骨髓抑制增加，肌酐清除率（CrCl）<45 ml/min的患者不建议使用培美曲塞。本研究的主要目的是确定在CrCl<45 ml/min的患者中降低剂量的培美曲塞的安全性。
这是一项回顾性病例系列研究，描述了俄亥俄州立大学詹姆斯癌症医院和索洛维研究所对CrCl<45 ml/min的患者使用降低剂量的培美曲塞治疗后3级或更高毒性的发生率。
共纳入18例患者。7例（39%）患者出现≥3级毒性。只有18%的给药导致≥3级毒性。4例（22%）患者出现≥3级血液学毒性；其中3例同时接受铂类药物治疗。第四例患者的CrCl<30 ml/min。没有CrCl>30 ml/min的接受单药培美曲塞治疗的患者出现≥3级血液学毒性。
对于CrCl在30至45 ml/min之间的患者，可以谨慎给予剂量调整后的培美曲塞。对于同时接受铂类药物化疗的患者以及CrCl<30 ml/min的患者，需要格外谨慎。对于CrCl<30 ml/min的患者，不建议常规推荐培美曲塞联合铂类药物治疗。
