Language：English   Publisher：Pharmacotherapy  

Background: Oxaliplatin-induced peripheral neuropathy (OIPN) is a major clinical challenge because it leads to discontinuation of chemotherapy. Omeprazole, a proton pump inhibitor (PPI), has been shown to prevent OIPN in a rat model. Therefore, we aimed to test whether the concomitant use of a PPI reduces oxaliplatin discontinuation due to OIPN. Methods: This retrospective study used data from 1015 patients who started treatment with oxaliplatin and evaluated two cohorts (PPI vs. non-PPI). The primary outcome measure was oxaliplatin discontinuation due to OIPN. A Kaplan–Meier curve was generated for cumulative doses and evaluated using the log-rank test and Cox proportional hazards analysis. Results: The log-rank test showed that the number of patients who discontinued oxaliplatin due to OIPN was significantly lower in the PPI group (p = 0.0264). Cox proportional hazards analysis incorporated and analyzed factors previously reported as potentially affecting neuropathy (sex, age, use of PPIs, calcium channel antagonists, opioids and adjuvant analgesics, and the CAPOX [capecitabine + oxaliplatin] regimen). The analysis suggested that the concomitant use of PPIs was a factor in reducing oxaliplatin discontinuation (adjusted hazard ratio [HR] = 0.568, 95% confidence interval [CI], 0.344–0.937, p = 0.0269). Since there were significant differences in some patient demographics between the two groups, propensity score matching was performed to align the patient demographics and then reanalyzed. After propensity score matching, the same analysis as above showed that oxaliplatin discontinuation due to OIPN was significantly less common in the PPI group (p = 0.0081); cox proportional hazards analysis showed that PPI use was a factor that significantly reduced oxaliplatin discontinuation due to OIPN (adjusted HR = 0.478, 95% CI, 0.273–0.836, p = 0.0096). Conclusions: These results suggest that concomitant PPI use may reduce oxaliplatin discontinuation due to OIPN in patients receiving oxaliplatin.

DOI： 10.1002/phar.70028

Web of Science

Scopus

PubMed

Language：English   Publisher：Supportive Care in Cancer  

Purpose: Paclitaxel and albumin-bound paclitaxel are important anticancer drugs for the treatment of non-small cell lung, pancreatic, gastric, and gynecological cancers; however, they cause peripheral neuropathy as an adverse reaction. Therefore, prophylaxis and treatment for peripheral neuropathy are needed, since there are no sufficient evidence-based strategies to prevent it. Our previous animal research and adverse effect database analysis studies have identified the potential of α1 antagonists to attenuate paclitaxel-induced peripheral neuropathy (PIPN). The purpose of the present study was to investigate the prophylactic potential of α1 antagonists for PIPN in patients with cancer. Methods: Data were collected from the medical records of 673 male patients aged 18 years and older who started treatment with paclitaxel- or albumin-bound paclitaxel-containing regimens at Kyushu University Hospital between January 1, 2013, and December 31, 2019. The two primary outcome measures were PIPN occurrence and paclitaxel discontinuation due to PIPN. Kaplan–Meier curves were generated for cumulative doses and evaluated using the log-rank test. Results: The percentage of patients in whom PIPN occurred (any grade) during the entire study period was 37.4% and 20.0% in without and with α1-receptor antagonist groups, respectively (P = 0.0101, χ2 test). The incidence of PIPN (any grade) was significantly lower in the α1 antagonists combination group (N = 55) than in the no α1-receptor antagonists group (N = 618) (P = 0.0425, log-rank test). However, there were no significant differences between the two groups in the discontinuation of paclitaxel due to PIPN (P = 0.9654). Conclusions: The present retrospective cohort study may suggest that concomitant use of α1-receptor antagonists may moderate the development of PIPN.

DOI： 10.1007/s00520-025-09368-y

Web of Science

Scopus

PubMed

Language：English   Publisher：Journal of Pharmacological Sciences  

Paclitaxel induces peripheral neuropathy, which is considered a dose-limiting factor. However, appropriate prophylactic agents are currently unavailable. We investigated the prophylactic effects of calmangafodipir, a superoxide dismutase mimetic, on paclitaxel-induced peripheral neuropathy using a male rat model. Repeated administration of paclitaxel (6 mg/kg, intraperitoneal, once weekly for 4 weeks) resulted in mechanical allodynia in the von Frey test and axonal degeneration in the sciatic nerve. Conversely, calmangafodipir (1–10 mg/kg, intravenous, thrice weekly for 4 weeks) prevented mechanical allodynia and axonal degeneration induced by paclitaxel. These results suggest that calmangafodipir may inhibit paclitaxel-induced peripheral neuropathy.

DOI： 10.1016/j.jphs.2024.11.004

Web of Science

Scopus

PubMed

Language：Japanese   Publisher：(一社)日本臨床腫瘍薬学会  

アベマシクリブはクレアチニンの尿細管分泌を阻害するが、アベマシクリブ投与後に血清クレアチニン(Scr)値が投与前の1.4倍まで上昇を認めたとしても、減量や休薬の対処が必要ないとされている。本研究ではアベマシクリブが投与された乳癌患者116名を対象に投与4週目のScr上昇率で2群(1.4倍以下群、1.4倍超群)に分け患者背景、効果および副作用との関連を調査した。その結果、投与4週目のScr上昇率にアベマシクリブ投与前の腎機能の影響は認められなかった。治療効果では、無増悪生存期間中央値が1.4倍以下群463日、1.4倍超群309日で差は認めなかった。また、副作用では、投与4週目または8週目までのアベマシクリブの減量・休薬は1.4倍以下群で有意に多く、1.4倍以下群で重篤な骨髄抑制が多く認められた。骨髄抑制発生状況の違いが、両群の減量・休薬率の差に影響を及ぼした可能性が示唆された。(著者抄録)

Language：English   Publishing type：Research paper (scientific journal)  

Event date： 2024.4

Language：Japanese  

Country：Japan  

Event date： 2024.4

Language：Japanese  

Country：Japan  

Event date： 2024.4

Language：Japanese  

Country：Japan  

Event date： 2024.4

Language：Japanese  

Country：United States  

Event date： 2024.4

Language：Japanese  

Country：Japan  

九州大学病院薬剤部における病院実務実習の指導を担当

2024年度, 九州大学病院 薬剤部 委嘱講師.