ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000530381
Yuan Yuan Shi, Long Su, Zeng Yan Liu, Yi Geng Cao, Xin Chen, Rong Li Zhang, Qing Zhen Liu, Jian Feng Yao, Wei Hua Zhai, Qiao Ling Ma, Er Lie Jiang, Ming Zhe Han
{"title":"A 7-Day Decitabine-Included Conditioning Regimen Accelerated Donor Hematopoietic Engraftment while Reduced the Occurrence of Mucositis without Interfering with Prognosis.","authors":"Yuan Yuan Shi, Long Su, Zeng Yan Liu, Yi Geng Cao, Xin Chen, Rong Li Zhang, Qing Zhen Liu, Jian Feng Yao, Wei Hua Zhai, Qiao Ling Ma, Er Lie Jiang, Ming Zhe Han","doi":"10.1159/000530381","DOIUrl":"https://doi.org/10.1159/000530381","url":null,"abstract":"<p><strong>Introduction: </strong>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard and curative treatment strategy for patients with hematologic malignancies. Recently, decitabine-included regimens have been investigated by several studies including ours, which may prevent relapse of primary malignant diseases.</p><p><strong>Methods: </strong>This study was to retrospectively evaluate a 7-day decitabine-included regimen with reduced dose of idarubicin for patients with hematologic malignancies who underwent allo-HSCT.</p><p><strong>Results: </strong>A total of 84 patients were enrolled, including 24 cases in 7-day and 60 cases in 5-day decitabine groups, respectively. Patients conditioned with 7-day decitabine regimen showed accelerated neutrophil (12.05 ± 1.97 vs. 13.86 ± 3.15; u = 9.309, p < 0.001) and platelet (16.32 ± 6.27 vs. 21.37 ± 8.57; u = 8.887, p < 0.001) engraftment compared with those treated with 5-day decitabine regimen. Patients in the 7-day decitabine group showed a significantly lower incidence rate of total (50.00% [12/24] versus 78.33% [47/60]; χ2 = 6.583, p = 0.010) and grade III or above (4.17% [1/24] vs. 31.67% [19/60]; χ2 = 7.147, p = 0.008) oral mucositis compared to those in the 5-day decitabine group. However, the occurrence of other major complications post-allo-HSCT and outcomes of patients in these two groups were comparable.</p><p><strong>Conclusion: </strong>These results demonstrate that this 7-day decitabine-contained new conditioning regimen seems to be feasible and safe for patients with myeloid neoplasms who receive allo-HSCT, and a large-scale prospective study is needed to confirm the findings of this study.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000526490
Chih-Jung Chen, Hanh T H Nguyen, Chih-Hao Huang, Hwei-Chung Wang, Chen-Teng Wu, Yao-Chung Wu, Geng-Yan He, Chiahung Chou, Hsiang-Wen Lin, Liang-Chih Liu
{"title":"Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting.","authors":"Chih-Jung Chen, Hanh T H Nguyen, Chih-Hao Huang, Hwei-Chung Wang, Chen-Teng Wu, Yao-Chung Wu, Geng-Yan He, Chiahung Chou, Hsiang-Wen Lin, Liang-Chih Liu","doi":"10.1159/000526490","DOIUrl":"https://doi.org/10.1159/000526490","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients.</p><p><strong>Methods: </strong>This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed.</p><p><strong>Results: </strong>Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%).</p><p><strong>Conclusions: </strong>The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10603977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01Epub Date: 2023-05-07DOI: 10.1159/000530894
Giovanni Gherardi, Pier Luigi Surico, Marco Coassin, Antonio Di Zazzo, Silvia D'Arezzo, Silvia Angeletti, Carla Fontana, Nicola Petrosillo
{"title":"Meningococcal Conjunctivitis in a 54-Year-Old Man: Case Report and Review of the Literature.","authors":"Giovanni Gherardi, Pier Luigi Surico, Marco Coassin, Antonio Di Zazzo, Silvia D'Arezzo, Silvia Angeletti, Carla Fontana, Nicola Petrosillo","doi":"10.1159/000530894","DOIUrl":"10.1159/000530894","url":null,"abstract":"<p><p>Neisseria meningitidis represents an uncommon pathogen of acute bacterial conjunctivitis. In this brief report, we describe a case of meningococcal conjunctivitis in an immunocompetent adult male, with a review of the literature. The patient went to the outpatient ophthalmology clinic complaining of severe ocular discomfort, burning, and redness for more than 2 weeks and, at slit lamp examination, he was diagnosed with a mild conjunctivitis. Microbiology cultures of ocular swabs revealed the growth of colonies, as pure culture, identified as N. meningitidis of serogroup B. A diagnosis of primary meningococcal conjunctivitis was made and treatment of patient with intramuscular injections of ceftriaxone in addition to topical moxifloxacin eye drops for 2 weeks led to clinical improvement and, finally, to a complete recovery, in accordance with microbiological findings. Ophthalmologists must be aware of the possibility of primary meningococcal conjunctivitis cases, even uncommon, and the need to treat with systemic antibiotics and their close contacts with adequate antibiotic chemoprophylaxis.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000525906
Zhi Rao, Zhong-Fang He, Mao-Hua Zheng, Zi-Long Dang, Gang Yang, Yong-Hong Zhang, Ning Lu, Yu-Hui Wei
{"title":"Fusidic Acid and Its Major Active Metabolite Penetration into Cerebrospinal Fluid for Assessing Treatment of Intracranial Infections.","authors":"Zhi Rao, Zhong-Fang He, Mao-Hua Zheng, Zi-Long Dang, Gang Yang, Yong-Hong Zhang, Ning Lu, Yu-Hui Wei","doi":"10.1159/000525906","DOIUrl":"https://doi.org/10.1159/000525906","url":null,"abstract":"<p><p>Fusidic acid (FA) had excellent antimicrobial effects due to its unique mechanism of action. Since 1962, FA has been widely used in the systemic and topical treatment of staphylococcal infections and exhibits a well-characterized potency against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative Staphylococci. In view of the spectrum of activity, no cross-resistance with other clinically used antibiotics, and potential penetration into brain tissue, FA was used to treat possible gra-positive bacteria in 3 patients with intracranial infections in the present report. FA and its active metabolite (3-keto FA) were measured in plasma and cerebrospinal fluid (CSF) to assess the treatment of FA, and the results indicated that 1,500 mg per day of FA was sufficient to achieve therapeutic concentrations in both plasma and CSF in intracranial infection patients, while the dosage did not experience unexpected regimen-related toxicity.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Initial Therapeutic Approach with Pembrolizumab in Synchronous Multiple Cancers, Including Non-Small Cell Lung Cancer, Highly Positive for Programmed Death-Ligand 1 Expression.","authors":"Tomonobu Koizumi, Shintaro Kanda, Takashi Kobayashi, Yoh-Ichiro Iwasa, Akemi Matsuo","doi":"10.1159/000528592","DOIUrl":"https://doi.org/10.1159/000528592","url":null,"abstract":"<p><p>Treatment of synchronous multiple primary cancers is clinically difficult. We report four cases of synchronous primary cancers, including advanced and metastatic non-small cell lung cancer (NSCLCs) highly positive for programmed death ligand-1 (PD-L1) expression and initially treated with pembrolizumab. Pembrolizumab was efficacious in 2 patients with NSCLC lesions, followed by chemoradiotherapy for esophageal cancer (case 1) and chemotherapy for gastric cancer (case 2). Both cancers in case 1 showed a complete response for 3 years, while progression of the accompanying gastric cancer resulted in mortality at 20 months in case 2. Both NSCLC and gastric cancer in case 3 failed to respond to pembrolizumab, but the accompanying laryngeal cancer in case 4 showed a complete response, and cytotoxic chemotherapy for NSCLC was continued for 18.0 months. Our clinical experience suggests that pembrolizumab is a useful therapeutic approach for patients with synchronous cancers, including NSCLC that highly expresses PD-L1.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01Epub Date: 2023-06-21DOI: 10.1159/000531606
Minas Sakellakis
{"title":"Why Metformin Should Not Be Used as an Oxidative Phosphorylation Inhibitor in Cancer Patients.","authors":"Minas Sakellakis","doi":"10.1159/000531606","DOIUrl":"10.1159/000531606","url":null,"abstract":"<p><strong>Background: </strong>Preclinical studies have suggested that metformin exerts antitumor effects on various types of cancers. However, the results of human clinical trials have been inconsistent.</p><p><strong>Summary: </strong>Metformin is widely considered to be a prime example of a clinically relevant compound that inhibits oxidative phosphorylation (OXPHOS). However, the efficacy of metformin in inhibiting OXPHOS in cancer patients remains uncertain. The available evidence suggests that the plasma concentration of metformin remains within the micromolar range when administered at therapeutic doses. While millimolar concentrations are necessary to inhibit complex I activity in isolated mitochondria, there is no evidence supporting the idea that metformin accumulates within the mitochondria. Metformin exerts a modest effect on the adenosine diphosphate to adenosine triphosphate (ATP) ratio, resulting in AMP-activated protein kinase activation, which promotes ATP-generating catabolic pathways and restores cellular energy balance.</p><p><strong>Key messages: </strong>The value of metformin as an OXPHOS inhibitor for cancer treatment is debatable, and caution should be exercised while using metformin for this purpose.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01Epub Date: 2022-07-26DOI: 10.1159/000525481
Ryan Morse, Rohit G Ganju, Rishi Neeranjun, Gregory N Gan, Ying Cao, Prakash Neupane, Kiran Kakarala, Yelizaveta Shnayder, Christopher E Lominska
{"title":"Treatment Tolerance of Cetuximab versus Alternative Chemotherapy Agents in Non-Cisplatin Candidates with Head and Neck Cancer Receiving Concurrent Chemoradiotherapy.","authors":"Ryan Morse, Rohit G Ganju, Rishi Neeranjun, Gregory N Gan, Ying Cao, Prakash Neupane, Kiran Kakarala, Yelizaveta Shnayder, Christopher E Lominska","doi":"10.1159/000525481","DOIUrl":"10.1159/000525481","url":null,"abstract":"<p><strong>Introduction: </strong>Standard of care for radiosensitization in head and neck squamous cell carcinoma (HNSCC) is concurrent chemoradiotherapy (CCRT) with high-dose cisplatin. The optimal chemoradiation regimen for patients medically unfit for cisplatin is unclear. We compared our experience with concurrent cetuximab (CTX) versus other cytotoxic non-cisplatin agents.</p><p><strong>Methods: </strong>We reviewed 53 patients between 2011 and 2017 with HNSCC treated with CCRT ineligible for cisplatin. Chemotherapy and radiotherapy treatment tolerance was evaluated in those receiving CTX versus non-CTX chemotherapy (NCC). Of the NCC regimens, the majority were carboplatin/paclitaxel and were dosed at an area under the curve (AUC) of 2 and 45-50 mg/m2, respectively. Standard radiation dosing was 70 Gray (Gy) in the definitive setting and 60-66 Gy in the postoperative setting. Patient characteristics and treatment toxicities were evaluated using categorical methods.</p><p><strong>Results: </strong>Patients were well balanced overall including differences between performance status and the comorbidity score. NCC patients experienced more radiation treatment breaks (52.4% vs. 21.9%, p = 0.022), radiation delays >1 week (33.3% vs. 3.1%, p < 0.01), and chemotherapy dose-limiting toxicity (61.9% vs. 28.1%, p = 0.015) compared to CTX patients. Nutritional dependence on a PEG tube was more likely in the NCC cohort (52.4% vs. 22.6%, p = 0.027).</p><p><strong>Conclusion: </strong>Our results suggest decreased treatment tolerance in non-cisplatin cytotoxic chemotherapy compared to cetuximab. Further prospective study is needed to clarify optimal chemotherapy in patients unable to receive cisplatin.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10280235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy.","authors":"Ryota Maeyama, Masaomi Ikeda, Soichiro Shimura, Noriyuki Amano, Yasukiyo Murakami, Yasufumi Yamada, Dai Koguchi, Takashi Tachibana, Mizuho Kawamura, Yusuke Sakata, Masahiro Hagiwara, Kazumasa Matsumoto, Masatsugu Iwamura","doi":"10.1159/000524449","DOIUrl":"10.1159/000524449","url":null,"abstract":"<p><strong>Background: </strong>There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC.</p><p><strong>Patients and methods: </strong>This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model.</p><p><strong>Results: </strong>The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor.</p><p><strong>Conclusion: </strong>Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90046269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01DOI: 10.1159/000529134
Xianting Li, Xiaojiao Chen, Chendong Fu, Ming Xie, Shurui Ouyang
{"title":"Long Non-Coding RNA BCAR4 Promotes Oxaliplatin Resistance in Colorectal Cancer by Modulating miR-484-3p/RAB5C Expression.","authors":"Xianting Li, Xiaojiao Chen, Chendong Fu, Ming Xie, Shurui Ouyang","doi":"10.1159/000529134","DOIUrl":"https://doi.org/10.1159/000529134","url":null,"abstract":"<p><strong>Background: </strong>Oxaliplatin-based chemotherapy resistance is a major cause of recurrence in patients with colorectal cancer (CRC). Increasing evidence indicates that lncRNA BCAR4 is involved in the occurrence and development of various cancers. However, the effect of BCAR4 on CRC chemotherapy resistance remains unclear.</p><p><strong>Methods: </strong>Real-time quantitative PCR and Western blotting were used to detect the expression levels of gene and protein, respectively. The role of BCAR4 in drug resistance was evaluated by cell viability and apoptosis experiments. Luciferase reporter assay and Western blot analysis confirmed the relationship between BCAR4, miR-483-3p, and RAB5C.</p><p><strong>Results: </strong>Luciferase reporter assay and Western blotting analysis confirmed the relationship among BCAR4, miR-483-3p, and RAB5C. The results showed that the expression levels of BCAR4 and RAB5C were increased in CRC tumor tissue. The expression levels of BCAR4 were increased in patients with chemotherapy resistance. Functional analysis showed that knockdown of BCAR4 reduced the expression levels of proteins related to stemness, decreased the activity of cells, and promoted apoptosis of CRC cells, while overexpression of RAB5C reversed these effects. Moreover, the results showed that BCAR4 promoted oxaliplatin resistance by inhibiting cell apoptosis. Mechanistically, BCAR4 sponged miR-483-3p and promoted the expression of RAB5C. Knockdown of BCAR4 reduced tumor size and enhanced cell sensitivity to oxaliplatin in vivo.</p><p><strong>Conclusion: </strong>The results suggested that BCAR4/miR-483-3p/RAB5C axis has the potential to be explored as a novel therapeutic target for CRC treatment.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10574620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ChemotherapyPub Date : 2023-01-01Epub Date: 2022-11-29DOI: 10.1159/000528063
Marie Moussouni, Véronique Graff, Franck Couturier, Hugo Herrscher
{"title":"Drug Interactions Causing Warfarin Overdose in a Patient with Pancreatic Cancer: A Case Report.","authors":"Marie Moussouni, Véronique Graff, Franck Couturier, Hugo Herrscher","doi":"10.1159/000528063","DOIUrl":"10.1159/000528063","url":null,"abstract":"<p><p>Mistletoe, Viscum album, is a medicinal plant used in complementary medicine in oncology. Patients do not necessarily mention to their oncologist this phytotherapeutic treatment which may be responsible for unsuspected drug interactions. Some patients are adept at taking medicinal plants, a practice often unknown to health professionals who take care of them. This case reports drug interactions leading to bleeding secondary to warfarin overdose. A patient over 75 years of age was treated with nab-paclitaxel and gemcitabine as a first course for metastatic pancreatic adenocarcinoma (day 0). He was also treated with warfarin for atrial fibrillation. At day 3, he reported faintness and melena. At day 5, the biological assessment revealed anemia with hemoglobinemia of 5.1 g/dL and an international normalized ratio of 7.3, indicating vitamin K antagonist (VKA) overdose. Warfarin was discontinued and the patient received vitamin K supplementation and transfusions. The final diagnosis was an anemic syndrome due to gastrointestinal bleeding secondary to VKA overdose. Based on the chronology, a drug interaction between chemotherapy and warfarin was first suspected. Then, the patient interview found out that he self-medicated with subcutaneous injections of mistletoe extracts: 10 mg on day 0 and on day 2. Nab-paclitaxel can displace warfarin from its albumin binding sites and increase the free and active concentration of warfarin. Mistletoe extracts (V. album) are used as complementary medicine in oncology. Warfarin is predominantly metabolized in the liver by 1A2, 2C9, and 3A4 cytochrome P450 (CYP) isoforms. An inhibitor of these cytochromes prevents the degradation of warfarin into inactive metabolites, leading to accumulation or even overdose of this narrow therapeutic index VKA. Nab-paclitaxel and gemcitabine do not act on these cytochromes. V. album is a cytochrome P450 3A4 inhibitor which therefore probably led to an increase in exposure to warfarin. Thus, there are two pharmacokinetic hypotheses that may explain warfarin overdose: the displacement of warfarin from its albumin binding sites or the inhibition of CYP3A4 by mistletoe. This adverse drug event was reported to the Regional Pharmacovigilance Center of Strasbourg on June 30, 2021, and registered under the number ST20212767.</p>","PeriodicalId":10047,"journal":{"name":"Chemotherapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}