Drug Interactions In Cancer Patients Research Articles

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery.

Monoclonal antibody-based immunotherapy targeting tumor antigens is now a mainstay of cancer treatment. One of the clinically relevant mechanisms of action of the antibodies is antibody-dependent cellular cytotoxicity (ADCC), where the antibody binds to the cancer cells and engages the cellular component of the immune system, e.g., natural killer (NK) cells, to kill the tumor cells. The effectiveness of these therapies could be improved by identifying adjuvant compounds that increase the sensitivity of the cancer cells or the potency of the immune cells. In addition, undiscovered drug interactions in cancer patients co-medicated for previous conditions or cancer-associated symptoms may determine the success of the antibody therapy; therefore, such unwanted drug interactions need to be eliminated. With these goals in mind, we created a cancer ADCC model and describe here a simple protocol to find ADCC-modulating drugs. Since 3D models such as cancer cell spheroids are superior to 2D cultures in predicting in vivo responses of tumors to anticancer therapies, spheroid co-cultures of EGFP-expressing HER2+ JIMT-1 breast cancer cells and the NK92.CD16 cell lines were set up and induced with Trastuzumab, a monoclonal antibody clinically approved against HER2-positive breast cancer. JIMT-1 spheroids were allowed to form in cell-repellent U-bottom 96-well plates. On day 3, NK cells and Trastuzumab were added. The spheroids were then stained with Annexin V-Alexa 647 to measure apoptotic cell death, which was quantitated in the peripheral zone of the spheroids with an automated microscope. The applicability of our assay to identify ADCC-modulating molecules is demonstrated by showing that Sunitinib, a receptor tyrosine kinase inhibitor approved by the FDA against metastatic cancer, almost completely abolishes ADCC. The generation of the spheroids and image acquisition and analysis pipelines are compatible with high-throughput screening for ADCC-modulating compounds in cancer cell spheroids.

Mitigating the Risk of Drug Interactions in Cancer Patients Taking Oral Anticancer Agents: The Role of a Multidisciplinary Team-Based Medication Reconciliation.

Polypharmacy in cancer patients is a recognized issue and should be an integral part of comprehensive patient assessment and management. Despite this, a systematic review of concomitant drugs or a search for potential drug-drug interactions (DDIs) is not always performed. Here, we present the results of a medication reconciliation model performed by a multidisciplinary team to identify clinically meaningful potential DDIs (defined by the presence of DDIof major severity or contraindication) in cancer patients undergoing oral antineoplastic drugs. From June to December 2022, we performed a non-interventional, prospective, cross-sectional, single-center study of adult cancer patients, initiating or undergoing treatment with oral antineoplastic drugs, referred by their oncologists for therapeutic review regarding potential DDIs. DDIs were assessed by a multidisciplinary team of hospital pharmacists and medical oncologists, through research in three different drug databases as well as in the summary of product characteristics. A report detailing all potential DDIs was created for each request and provided to the patient's medical oncologist for further examination. Overall, 142 patients' medications were reviewed. Regardless of the severity or clinical importance, 70.4% of patients had at least one potential DDI. We found 184 combinations of oral anticancer and regular therapy agents with potential DDIs, 55 of whom were considered of major severity by at least one DDI database. As expected, the number of potential DDIs increased with the number of active substances in regular therapy (p <0.001), but we did not find an increased relation between age and the total number of potential DDIs (p =0.109). Thirty-nine (27.5%) patients had at least one clinically meaningful DDI identified. After adjustment through multivariable logistic regression, only the female sex (odds ratio (OR) 3.01,p= 0.029), the number of active comorbidities (OR 0.60,p= 0.029), and the presence of proton pump inhibitors in chronic medication (OR 2.99,p= 0.033) remained as predictors of potential meaningful DDI. Although drug interactions are a concern in oncology, a systematic DDI review is rarely conducted in medical oncology consultations. The availability of a medication reconciliation service, carried out by a multidisciplinary team with dedicated time for this task, is an added value for safety enhancement in cancer patients.

A comprehensive evaluation of potentially significant drug-drug, drug-herb, and drug-food interactions among cancer patients receiving anticancer drugs

IntroductionDuring the cancer treatment path, cancer patients use numerous drugs, including anticancer, supportive, and other prescribed medications, along with herbs and certain products. This puts them at risk of significant drug interactions (DIs). This study describes DIs in cancer patients and their prevalence and predictors.MethodsA cross-sectional study design was used to achieve the study objectives. The study was carried out in two centers in the northern West Bank, Palestine. The Lexicomp® Drug Interactions tool (Lexi-Comp, Hudson OH, USA) was applied to check the potential DIs. In addition, the Statistical Package for the Social Sciences (SPSS) was used to show the results and find the associations.ResultsThe final analysis included 327 patients. Most of the participants were older than 50 years (61.2%), female (68.5%), and had a solid tumor (74.6%). The total number of potential DIs was 1753, including 1510 drug-drug interactions (DDIs), 24 drug-herb interactions, and 219 drug-food interactions. Importantly, the prevalence of DDIs was 88.1%. In multivariate analysis, the number of potential DDIs significantly decreased with the duration of treatment (p = 0.007), while it increased with the number of comorbidities (p < 0.001) and the number of drugs used (p < 0.001).ConclusionsWe found a high prevalence of DIs among cancer patients. This required health care providers to develop a comprehensive protocol to monitor and evaluate DIs by improving doctor-pharmacist communication and supporting the role of clinical pharmacists.

Polypharmacy and Drug Interactions in Cancer Patients

Amaç: Kanser hastaları, sitotoksik ajanlar başta olmak üzere pek çok ilacın uygulanması nedeniyle ilaç-ilaç etkileşimleri açısından önemli bir risk altındadır. Çalışmada kanser hastalarının polifarmasi ve potansiyel ilaç-ilaç etkileşimleri bakımından mercek altına alınması amaçlanmıştır.Yöntem: Araştırma, 18 yaşından büyük, kemoterapi tedavisi görmekte olan 202 adet gönüllü kanser hastası ile gerçekleştirildi. Kanser türü, ilaç kullanımı ve demografik bilgiler hasta bilgi formları ile hasta tedavi dosyalarından temin edildi. İlaçlar arasındaki etkileşimler Rx Media Pharma® programı ve www.drugs.com ilaç etkileşimi sorgulama web sitesi kullanılarak belirlendi. p&amp;lt;0.05 istatistiksel olarak anlamlı kabul edildi. Bulgular: Çalışmada, bir kanser hastasının ortalama olarak sekiz ilaç kullanmakta olduğu ve %82.7’sin de polifarmasi varlığı saptandı. Çalışmada, hasta başına yaklaşık 3.5 ilaç-ilaç etkileşimi tespit edildi. Bu etkileşimlerin %85’inin klinik olarak dikkate alınması gereken orta ve yüksek düzey etkileşimler olduğu belirlendi. Kanser türleri içerisinde toplamda en az ilaç kullanan grubun meme tümörlü hastalar olduğu saptandı ve bunun bir sonucu olarak diğer tümör tiplerine sahip hastalara göre daha az ilaç etkileşimi olduğu belirlendi (p=0.01). Katılımcıların %48’inin kanser haricinde en az bir komorbiditeye sahip olduğu tespit edildi.Sonuç: Araştırmada kanser hastalarında komorbidite ve polifarmasinin oldukça yaygın olduğu tespit edildi. Polifarmasinin bir sonucu olarak kanser hastaları arasında önemli miktarda ilaç–ilaç etkileşimleri olduğu saptandı. İlaç etkileşimlerinin engellenmesi için tüm paydaşlara önemli sorumluluklar düşmekte ve bu konuda çok merkezli çalışmalara ihtiyaç bulunmaktadır.

Drug interactions in cancer patients: A hidden risk?

Drug interactions in cancer patients: A hidden risk?

Role of clinical pharmacists to prevent drug interactions in cancer outpatients: a single-centre experience.

Cancer patients are especially vulnerable to drug interactions, which may alter the efficacy and toxicity of treatment, leading to severe clinical consequences. Determine the incidence of such interactions in patients receiving chemotherapy, as well as to identify the drugs most frequently involved, investigate the influence of the pharmacist's interventions and verify the degree of acceptance of pharmacist's recommendations by the medical team. The oncology department of a Spanish tertiary hospital. During 3 months, all the drug interactions in the regular combined with treatment for cancer were analysed using two databases, and recommendations were made when clinically significant interactions (CSI) were identified. Incidence of CSI in oncology outpatients; drugs involved in CSI. Of the 75 patients included, 31 (41%) presented CSI. Most interactions were among drugs included in the patient's usual treatment. The principal drug groups involved in CSI were cytostatic agents, antiemetics and antidepressants. The hospital pharmacist intervened on 20 occasions (35% of the patients presenting drug interactions). These interventions mainly focused on recommendations to modify or discontinue drug prescriptions, and were followed in 94% of cases. The incidence of drug interactions in cancer patients is high, and they most often involve medications to treat comorbid conditions. The pharmacist, as a member of the multidisciplinary team, can contribute significantly by checking the treatment prescribed and detecting interactions, to reduce medication-related problems and to optimise drug therapy for these patients.

Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs

Background:Potential drug–drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment.Methods:A search was conducted in a computer-based medication prescription system for dispensing oral anticancer drugs to outpatients in three Dutch centres. Potential drug–drug interactions were identified using electronic (Drug Interaction Fact software) and manual screening methods (peer-reviewed reports).Results:In the 898 patients included in the study, 1359 PDDIs were identified in 426 patients (46%, 95% confidence interval (CI)=42–50%). In 143 patients (16%), a major PDDI was identified. The drug classes most frequently involved in a major PDDI were coumarins and opioids. The majority of cases concerned central nervous system interactions, PDDIs that can cause gastrointestinal toxicity and prolongation of QT intervals. In multivariate analysis, concomitant use of more drugs (odds ratio (OR)=1.66, 95% CI=1.54–1.78, P<0001) and genito-urinary cancer (OR=0.25, 95% CI=0.12–0.52, P<0001) were risk factors.Conclusion:Potential drug–drug interactions are very common among cancer patients on oral cancer therapy. Physicians and pharmacists should be more aware of these potential interactions.

1402P - Drug Interactions in Cancer Patients Treated with Oral Anti-Cancer Drugs

1402P - Drug Interactions in Cancer Patients Treated with Oral Anti-Cancer Drugs

Drug interactions in cancer patients receiving antidepressants are common, researchers report.

Drug interactions in cancer patients receiving antidepressants are common, researchers report.

Potential Drug Interactions in Cancer Patients Receiving Supportive Care Exclusively

Cancer patients at the end of life often take many medications and are at risk for drug interactions. The purpose of this study was to describe the epidemiology of potential drug interactions in cancer patients receiving supportive care exclusively. We retrospectively reviewed the charts of consecutive adult cancer outpatients attending palliative care clinics at the Princess Margaret Hospital, Toronto, Canada. Drugs were screened for interactions by the Drug Interaction Facts software, which classifies interactions by levels of severity (major, moderate, and minor) and scientific evidence (1–5, with 1 = the strongest level of evidence). Among 372 eligible patients, 250 potential drug interactions were identified in 115 patients (31%, 95% confidence interval 26%–36%). The most common involved warfarin and phenytoin. Most interactions were classified as being of moderate severity (59%) and 42% of them were supported by Levels 1–3 of evidence. In multivariable analysis, increasing age ( P < 0.001), presence of comorbidity ( P = 0.001), cancer type (brain tumors, P < 0.001), and increasing number of drugs ( P < 0.001) were associated with risk of drug interactions. Potential drug interactions are common in palliative care and mostly involve warfarin and anticonvulsants. Older patients, those with comorbid conditions, brain tumor patients, and those taking many medications are at greater risk of drug interactions.

Drug combinations with the potential to interact among cancer patients

Dear Dr. H. J. Senn, I really appreciated the recent article by Haddad et al. [1] published in the journal of Supportive Care in Cancer entitled “The pharmacological importance of cytochrome CYP3A4 in the palliation of symptoms: review and recommendations for avoiding adverse drug interactions.” The authors performed a comprehensive review of the literature on pharmacokinetic drug interactions between medications to palliate symptoms commonly prescribed to cancer patients that involve the CYP3A4 cytochrome enzyme. They described the most common interactions with CYP3A4 substrates, inducers, and inhibitors. They also gave examples of safer alternatives to commonly used medications. Drug interaction is a neglected issue in clinical practice, specifically in oncology [2]. Given the great tumor burden and the large number of medications that cancer patients receive [3] (anticancer and supportive care agents and drugs to treat comorbid illnesses), it is of prime importance to address and divulge drug interactions in this population. One theme that was not covered by Haddad et al. was the epidemiology of drug interactions in oncology. I have conducted three studies of potential drug interactions in cancer patients that can shed some light into the extent of this problem. Based on previous experience, I would like to briefly comment on these studies. The first study evaluated the frequency of potential drug interactions among 100 consecutive hospitalized patients with solid tumor and hematological malignancies not currently receiving antineoplastic therapy [4]. In that study, 63% of patients were exposed to at least one potential drug interaction. In the second study, we evaluated the frequency of drug combinations with the potential to interact among ambulatory patients with solid tumors receiving standard cancer-directed therapy [5]. Using a highly accurate software program, the Drug Interactions Facts version 4.0, we screened for and classified potential drug interactions by level of severity (major, moderate, minor) and scientific evidence (1 to 5, with 1 representing the strongest evidence). Among 405 patients, 276 potential drug interactions were identified in 27% of them. The majority of potential interactions involved non-anticancer agents (87%), were classified as either major or moderate (86%), and had good evidence in the literature (i.e., supported at least by several case reports, 52%) [5]. Most potential interactions related to antihypertensive agents, warfarin, aspirin and anticonvulsants. In both studies, more than 50% of interactions were pharmacokinetic. Our group has recently undertaken another survey of potential drug interactions among 255 cancer patients receiving exclusive palliative care. The results will be presented at the Multinational Association of Supportive Care in Cancer 2007. Our data suggest that drug combinations with the potential to interact are common among cancer patients, most are pharmacokinetic and usually involve medications to treat comorbid conditions such as warfarin, antihypertensive, and aspirin. These medications are routinely used Support Care Cancer (2007) 15:1113–1114 DOI 10.1007/s00520-007-0274-3

Epidemiology of drug interactions in cancer patients

Epidemiology of drug interactions in cancer patients

Epidemiology of drug interactions in cancer patients

Epidemiology of drug interactions in cancer patients

Drug interactions in ambulatory cancer patients receiving cancer-directed therapy

6129 Background: Cancer patients (pts) are susceptible to drug interactions (DI) because they receive multiple medications. Here we evaluate the epidemiology of potential DI in cancer patients. Methods: Ambulatory, adult pts with solid malignancies who were receiving antineoplastic treatment completed a questionnaire about drugs taken in the previous month. Drug Interactions Facts software was used to screen for potential DI and to classify them in terms of severity (major, moderate and minor, where major is a life-threatening interaction) and level of scientific evidence (1 to 5, with 1 being the highest level). Summary statistics and logistic regression were used to describe the results. Results: Between Sept -Dec 2005, 183 pts completed the questionnaire: median age was 61 (range 26–88), and 114 (62%) were women. Cancer sites included breast 63 (35%), gastrointestinal 45 (25%), and genitourinary 36 (20%). Treatment intent was palliative in 139 (60%). Most pts (76%) were receiving chemotherapy; 111 (66%) had at least one co-morbid condition, and 72 (47%) had abnormal liver and/or renal function. The median number of drugs per pt was 5 (range 0–16). Among the 183 pts, 131 potential DI were identified of which 65 (50%) were due to pharmacokinetic interactions. Sixteen (12%) of all potential DI were major, 94 (72%) were moderate, and 21 (16%) were minor. Fourteen (11%), 54 (41%), 5 (4%), 42 (32%), and 16 (12%) were supported by levels 1,2,3,4,5 of evidence respectively. Most potential DI involved non-chemotherapy agents such as warfarin, antihypertensives, and anti-inflammatory drugs. In multivariate analyses, number of comorbidities (p= .0001), number of drugs (p= .005), and cancer type (p= .03) were significant risk factors for DI. Conclusion: PotentialDI are common in oncology, and usually involve non-chemotherapeutic drugs. Risk factors for potential DI include comorbid illness, number of medications and type of cancer. Oncologists should be aware of such an important issue. No significant financial relationships to disclose.