Division of Oncology, Rambam Health Care Campus, Haifa, Israel.
Center for Malignant Diseases, Emek Medical Center, 21 Yitzhak Rabin Blvd, 1834111, Afula, Israel.
Cancer Chemother Pharmacol. 2019 Mar;83(3):545-550. doi: 10.1007/s00280-018-3758-6. Epub 2018 Dec 13.
In a previous study, we found that co-administration of proton pump inhibitors (PPIs) with cetuximab was associated with increased skin toxicity. Both these drugs can induce hypomagnesemia. The aim of this study was to retrospectively explore the possible influence of PPI drugs on cetuximab skin toxicity and the potential synergistic effect of hypomagnesemia.
The files of all eligible patients treated with cetuximab during 2015-2016 with metastatic colorectal carcinoma (mCRC) or head and neck (H&N) carcinoma were reviewed. The concomitant use of PPIs was defined if a drug belonging to that class was included in the patient's chronic medications list.
One hundred eighteen patients (61 with H&N carcinoma, 57 with mCRC) were included in the study, and 58 of the 118 patients received PPIs concomitantly with cetuximab. Skin toxicity of any grade was reported in 33/58 (56.9%) patients on PPIs compared with 22/60 (36.7%) patients (p = 0.08) with grade 3-4 in 19/58 (32.8%) and 2/60 (3.3%), respectively (p = 0.001). Hypomagnesemia (Mg serum level < 1.2 mg/dL) was reported in 14/58 (25.9%) PPI-treated patients, compared with 5/60 (10.4%) patients not on PPIs (p = 0.08). Grade 3-4 skin toxicity or hypomagnesemia (Mg < 0.9 mg/dL) was reported in 23/58 (39.7%) patients on concomitant treatment with PPIs, compared with 3/60 (5%) patients not on PPIs (p = 0.001).
Both the rate and the severity of cetuximab-induced skin toxicity and hypomagnesemia were increased by chronic concomitant administration of PPIs. A prospective study is needed to confirm the possible interaction between cetuximab and PPIs.
在之前的研究中，我们发现质子泵抑制剂（PPIs）与西妥昔单抗联合使用会导致皮肤毒性增加。这两种药物都可引起低镁血症。本研究旨在回顾性探讨 PPI 药物对西妥昔单抗皮肤毒性的可能影响，以及低镁血症的潜在协同作用。
回顾性分析了 2015 年至 2016 年间接受西妥昔单抗治疗的转移性结直肠癌（mCRC）或头颈部（H&N）癌患者的所有合格病例。如果患者的慢性用药清单中包含该类药物，则定义为同时使用 PPI。
共纳入 118 例患者（H&N 癌 61 例，mCRC 57 例），其中 58 例患者同时接受 PPI 和西妥昔单抗治疗。在接受 PPI 治疗的 58 例患者中，有 33 例（56.9%）出现任何级别的皮肤毒性，而在未接受 PPI 治疗的 60 例患者中，有 22 例（36.7%）出现皮肤毒性（p=0.08），其中 19 例（32.8%）为 3-4 级，2 例（3.3%）为 3-4 级（p=0.001）。在接受 PPI 治疗的 58 例患者中，有 14 例（25.9%）出现低镁血症（血清镁水平<1.2mg/dL），而在未接受 PPI 治疗的 60 例患者中，有 5 例（10.4%）出现低镁血症（p=0.08）。在同时接受 PPI 治疗的 58 例患者中，有 23 例（39.7%）出现 3-4 级皮肤毒性或低镁血症（镁<0.9mg/dL），而在未接受 PPI 治疗的 60 例患者中，有 3 例（5%）出现 3-4 级皮肤毒性或低镁血症（p=0.001）。
慢性同时使用 PPI 会增加西妥昔单抗引起的皮肤毒性和低镁血症的发生率和严重程度。需要进行前瞻性研究来证实西妥昔单抗和 PPI 之间的可能相互作用。
