60294Cross Cancer Institute, Edmonton, Canada.
Alberta Health Services, Calgary, Canada.
J Oncol Pharm Pract. 2022 Mar;28(2):457-461. doi: 10.1177/10781552211038031. Epub 2021 Sep 25.
Palliative care aims to improve the quality of life of patients with a life-limiting or life-threatening illness and is multifaceted involving comprehensive interdisciplinary assessments and interventions. Interdisciplinary palliative care in the setting of untreatable cancer diagnoses is of particular importance due to additional considerations that must be taken as patients are often undergoing palliative chemotherapy and/or radiation therapy. These patients' complexity warrants special considerations and attentiveness to drug-related problems.
The purpose of this case report is to highlight the importance of both complete and comprehensive medication histories in cancer care and the impact of proton pump inhibitors on pancreatic enzyme insufficiencies secondary to pancreatic cancers. This case involves a drug-related problem involving three medications that are commonly used in pancreatic cancer patients: pancreatic enzyme replacement therapy, a proton pump inhibitor, and a fluoroquinolone antibiotic. The patient presented in this case report is an 80-year-old man diagnosed with unresectable pancreatic cancer with a history of symptomatic gastroesophageal reflux disease managed with a proton pump inhibitor, specifically tablets of the 40 mg strength of pantoprazole magnesium taken orally once daily. During the patient's first of five 28-day cycles of palliative-intent chemotherapy with gemcitabine and -paclitaxel, the patient presented to the emergency department due to fever and, although not severely neutropenic, was prescribed amoxicillin/clavulanate and ciprofloxacin due to his advanced age. After reading a patient advisory on a ciprofloxacin patient information sheet that advised avoidance of concomitant administration of ciprofloxacin and magnesium, the patient self-discontinued his pantoprazole as it was a magnesium salt formulation. This discontinuation was followed by two weeks of persistent foul-smelling diarrhea, flatulence, and abdominal pain.
The patient's healthcare team symptomatically managed the patient with oral and intravenous rehydration unaware of the cause of the symptoms. A trial of pancreatic enzyme replacement therapy was initiated; however, it was unsuccessful in resolving his symptoms. After further investigation and a more in-depth patient interview, it was discovered that the discontinued proton pump inhibitor was likely the cause of the patient's new symptoms and was subsequently re-initiated. Pancreatic enzyme replacement therapy in combination with re-initiation of pantoprazole therapy essentially resolved all symptoms.
Before his diagnosis of unresectable pancreatic cancer, the patient had been on proton pump inhibitor therapy for nearly a decade. He had significant atrophy of the pancreas and an undoubtedly decreased pancreatic enzyme and bicarbonate production; however, he did not experience foul-smelling diarrhea indicative of pancreatic enzyme insufficiency while he was on his proton pump inhibitor. We believe that with his proton pump inhibitor therapy, he was unknowingly being partially treated for his worsening pancreatic enzyme insufficiency, specifically the component related to his lack of bicarbonate production and secretion. His discontinuation of his proton pump inhibitor led to a decrease in gastric acid, small bowel, and normal intraduodenal pH, which resulted in any remaining pancreatic enzyme reserve to become non-functional, unmasking his pancreatic enzyme insufficiency. An initial empiric trial of pancreatic enzyme replacement therapy failed in the absence of a proton pump inhibitor; however, within days of restarting his proton pump inhibitor along with pancreatic enzyme replacement therapy, his gastrointestinal symptoms completely resolved. This is due to the decrease of gastric and intraduodenal acidity, which better enabled the function of pancreatic enzymes present in pancreatic enzyme replacement therapy.
缓和医疗的目的是提高生命有限或生命受到威胁的患者的生活质量，其涉及多方面，包括全面的跨学科评估和干预。对于无法治疗的癌症诊断，姑息治疗中的跨学科方法尤为重要，因为患者通常正在接受姑息化疗和/或放射治疗，需要考虑更多因素。这些患者的复杂性需要特别考虑和注意与药物相关的问题。
本病例报告的目的是强调在癌症治疗中全面和完整的用药史的重要性，以及质子泵抑制剂对继发于胰腺癌的胰腺酶缺乏的影响。该病例涉及一种与三种常用于胰腺癌患者的药物相关的问题：胰腺酶替代疗法、质子泵抑制剂和氟喹诺酮类抗生素。本病例报告中的患者是一名 80 岁男性，被诊断为无法切除的胰腺癌，患有症状性胃食管反流病，用质子泵抑制剂治疗，具体为每天口服 40 毫克泮托拉唑镁片剂。在患者接受吉西他滨和紫杉醇姑息性化疗的五个 28 天周期中的第一次就诊时，因发热而到急诊就诊，尽管患者不是严重中性粒细胞减少症，但由于其年龄较大，被开了阿莫西林/克拉维酸和环丙沙星。在阅读环丙沙星患者信息表上的关于避免同时使用环丙沙星和镁的患者咨询后，患者自行停用了他的泮托拉唑，因为它是一种镁盐制剂。停用泮托拉唑后，患者出现了两周持续的恶臭腹泻、气胀和腹痛。
患者的医疗团队对患者进行了症状性治疗，进行了口服和静脉补液，而不知道症状的原因。开始尝试使用胰腺酶替代疗法；然而，它并没有成功缓解他的症状。经过进一步调查和更深入的患者访谈，发现停用的质子泵抑制剂可能是患者新症状的原因，并随后重新开始使用。胰腺酶替代疗法联合重新开始使用泮托拉唑治疗基本上解决了所有症状。
在被诊断为无法切除的胰腺癌之前，该患者已经使用质子泵抑制剂治疗了近十年。他的胰腺明显萎缩，无疑胰腺酶和碳酸氢盐的产生减少；然而，他在使用质子泵抑制剂时没有出现恶臭腹泻，表明他没有胰腺酶缺乏。我们认为，由于他的质子泵抑制剂治疗，他在不知不觉中接受了部分治疗，以改善他日益恶化的胰腺酶缺乏症，特别是与他缺乏碳酸氢盐产生和分泌有关的成分。他停用质子泵抑制剂导致胃酸、小肠和正常十二指肠内 pH 值降低，导致任何剩余的胰腺酶储备失去功能，暴露出他的胰腺酶缺乏症。在没有质子泵抑制剂的情况下，初始经验性胰腺酶替代疗法治疗失败；然而，在重新开始使用质子泵抑制剂和胰腺酶替代疗法的几天内，他的胃肠道症状完全缓解。这是由于胃酸和十二指肠内酸度降低，使胰腺酶替代疗法中存在的胰腺酶的功能得到更好的发挥。
