The burden of polypharmacy and drug–drug interactions in older cancer patients treated with immunotherapy

2021 ◽  
pp. 107815522110120
Author(s):  
Deniz C Guven ◽  
Gozde Kavgaci ◽  
Oktay H Aktepe ◽  
Hasan C Yildirim ◽  
Taha K Sahin ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cancer Patients ◽  
Injury Risk ◽  
Checkpoint Inhibitors ◽  
High Rate ◽  
Potentially Inappropriate Medications ◽  
Inappropriate Prescription ◽  
Prescription Practices ◽  
Increased Risk ◽  
Older Cancer Patients

Introduction Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. Methods A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. Results The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). Conclusion In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Phase 1A clinical trial of the first-in-class fascin inhibitor NP-G2-044 evaluating safety and anti-tumor activity in patients with advanced and metastatic solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2548-2548
Author(s):  
Vincent Chung ◽  
Komal L. Jhaveri ◽  
Daniel D. Von Hoff ◽  
Xin-Yun Huang ◽  
Edward Graeme Garmey ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Dendritic Cells ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Drug Synergism ◽  
Duration Of Treatment ◽  
Antigen Uptake ◽  
Increased Risk ◽  
Metastatic Activity

2548 Background: Fascin inhibitors block tumor metastasis and increase antigen uptake in intra-tumoral dendritic cells. Filopodia, finger-like protrusions on cell surfaces, are necessary for migration of metastatic tumor cells and intra-tumoral dendritic cells. Fascin is the primary actin cross-linker in filopodia and elevated levels correlate with increased risk of metastasis, disease progression and mortality. NP-G2-044 is a novel small molecule that inhibits function of fascin. Pre-clinical data demonstrate drug-associated reductions in tumor growth and metastasis, enhanced immune response and survival in treated animals, and drug-drug synergism when combined with anti-PD-1 antibodies. Methods: This multicenter phase 1A clinical trial was designed to evaluate safety and tolerability of NP-G2-044 and to identify the drug’s recommended phase 2 dose (RP2D) using a 3+3 dose escalation design. NP-G2-044 was administered to patients (pts.) with treatment-refractory solid tumor malignancies as a single oral daily dose for 6-week cycles that included 4 weeks on (daily dosing) and 2 weeks off (rest). Results: A total of 23 pts. were enrolled in 7 dose cohorts ranging from 200-2100 mg. QD. Overall, NP-G2-044 appeared well-absorbed and distributed with Tmax of ̃4 hrs and T1/2 of 20-24 hrs. Across all cohorts, no DLTs, drug-related SAEs or patient deaths were observed. Based on PK and safety findings, 1600 mg. daily was selected as the provisional RP2D. While no formal RECIST-based objective responses were observed, consistent with the drug’s non-cytotoxic mechanism of action, preliminary signals of anti-tumor and anti-metastatic activity were observed. These include dose proportional increases in duration of treatment, progression-free-survival, and metastasis-free interval, in particular for 4/4 late-stage ovarian cancer patients (table). Comparison of time on treatment (TOT) for ovarian cancer patients. Conclusions: In this first-in-human clinical trial, the novel fascin inhibitor, NP-G2-044, appeared safe and well tolerated. Signals of single-drug anti-tumor and anti-metastatic activity were observed. A phase 2A clinical trial with a particular focus on Ovarian Cancer will seek to elucidate signals of RP2D activity in both monotherapy and the combination of NP-G2-044 with anti-PD-(L)1 immune checkpoint inhibitors. Clinical trial information: NCT03199586. [Table: see text]

The use of warfarin for venous thromboembolism (VTE): Practical problems for patients and resource implications for an oncology unit

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6088-6088
Author(s):  
P. G. Morris ◽  
D. O’Dwyer ◽  
C. Davenport ◽  
C. O’Callaghan ◽  
O. S. Breathnach ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Warfarin Therapy ◽  
Oral Anticoagulants ◽  
Early Death ◽  
High Rate ◽  
Multiple Drug ◽  
Treatment Change ◽  
Oncology Unit

6088 Background: Recent evidence has suggested improved efficacy with low molecular weight heparin (LMWH) over oral coumarins for the treatment of cancer patients with VTE. Oral anticoagulants present multiple practical problems for patients undergoing chemotherapy, including side-effects, disruption of anticoagulation for invasive procedures, multiple drug interactions and multiplicity of patient visits. To assess the practice implications of these issues, a review was carried out in a busy medical oncology unit. Methods: A retrospective review of all patients treated with the coumarin derivative, warfarin for VTE during the last year was undertaken. Patients on prophylactic warfarin for central venous devices were excluded. Computerised laboratory records were used to identify patients. Patients were assessed for adverse events and therapeutic efficacy. The extra volume of work involved in monitoring blood tests and treating complications was quantified. Results: 55 patients with VTE were treated with warfarin from 07/01/04 to 06/30/05. The majority (73%) had metastatic carcinoma. 21 invasive interventions required disruption of anticoagulation. 90% of these were in patients with metastatic disease. Each patient was subtherapeutic (International normalised ratio <2.0) for a mean of 30.7 days (25% of mean duration of anticoagulation). There were 8 admissions for haemorrhage. Nine patients died on warfarin, 8 of whom had metastatic disease. In one patient with significant cardiac comorbidity warfarin therapy contributed to early death. No patterns of drug interactions were identified. A total of 1,369 coagulation tests were performed. There were 382 extra blood test visits, representing 26% of all day ward blood visits. On treatment, 13 patients (24%) were changed from warfarin therapy to LMWH. In 4 patients there was progression of VTE. In 9 patients, all with metastatic disease LMWH was substituted to qualitatively improve patient care by minimising hospital visits and facilitating home based care. Conclusions: This study identifies the high rate of treatment change to LMWH and quantifies the extra resource utilization with coumarin therapy. This supports the increased primary use of LMWH in selected cancer patients. No significant financial relationships to disclose.

Rates of immunosuppressive treatment and hospitalization after checkpoint inhibitor therapy in melanoma and lung cancer patients with autoimmune diseases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14140-e14140
Author(s):  
David Andrew Bender ◽  
Catherine Spina ◽  
Samuel P. Heilbroner ◽  
Eric Xanthopoulos ◽  
Tony J. C. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Autoimmune Diseases ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Oral Prednisone ◽  
Immunosuppressive Treatment ◽  
Lung Cancer Patients ◽  
Pharmacy Claims ◽  
Increased Risk

e14140 Background: Immune checkpoint inhibitors (ICIs) are known to cause immune-related adverse events. Patients with autoimmune diseases (AID) were excluded from most ICI clinical trials due to the potentially high risk of adverse effects. Data on the safety of ICIs in patients with a diagnosis of AID is therefore limited. Methods: A retrospective cohort study was conducted using a de-identified large oncology health care and pharmacy claims database with data from March 2010 until April 2017. Patients analyzed had a diagnosis of either melanoma or lung cancer and were treated with either of the anti-PD-1 inhibitors nivolumab or pembrolizumab. We assessed whether patients with AID compared with no AID were more likely to require medical interventions within 180 days of ICI therapy. We determined the percentage of patients receiving oral prednisone, IV methylprednisolone, or were hospitalized, which may represent responses to ICI toxicity. Results: 16.7% (16/96) of patients with either melanoma or lung cancer and AID received oral prednisone treatment within 180 days of ICI treatment, while 8.3% (131/1573) of patients without AID received oral prednisone during the same period. 8.4% (16/190) of patients with AID received IV methylprednisolone compared to 3.6% (79/2190) of patients without AID. Among melanoma patients, 24.1% (13/54) of patients with AID were hospitalized following ICI treatment, compared to 5.8% (28/480) of patients without ICI. Among lung cancer patients, 38.2% (52/136) of patients with AID were hospitalized compared to 31.6% (541/1711) of patients without AID. All comparisons are significant at p < 0.05 except hospitalizations in lung cancer patients. Conclusions: Patients with AID were more likely to receive interventions after ICI treatment that may represent responses to immune-related adverse events, suggesting that patients with AID are at increased risk for toxicity when being treated with ICIs.

scholarly journals Effect of Anxiety and Depression on Survival of Cancer Patients, a 13 Year Follow-up

2021 ◽  
Vol 6 (1) ◽  
pp. 9-13
Author(s):  
Suriati Mohamed Saini ◽  
Susan Tan Mooi Koon ◽  
Mohamad Adam Bujang ◽  
Gerard Lim Chin Chye ◽  
Shalisah Sharip ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Cancer Patients ◽  
Depression Scale ◽  
Cox Proportional Hazards ◽  
Anxiety Symptoms ◽  
High Rate ◽  
Anxiety And Depression ◽  
Risk Of Death ◽  
Increased Risk

Introduction: Anxiety and depression occur at a high rate in cancer patients. However, debate remains regarding the effect of anxiety and depression on cancer survival. Objective: This study aimed to determine the effect of anxiety and depressive symptoms on the survival of cancer patients. Methods: The subjects consisted of 112 cancer patients who attended the Oncology and Radiotherapy outpatient clinic Hospital Kuala Lumpur, Malaysia, in 1999. Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS) questionnaire at inception. Information on patients’ mortality status for extended 13 years follow-up (in 2011) was obtained from the National Registration Department death records. Overall survival for each anxiety and depressive symptoms scores in HADS at 13 years was calculated using Cox proportional hazards regression analysis. Results: Cancer patients experienced more anxiety (83%) compared to depressive symptoms (40.2%). The mean (S.D.) HADS scores for depressive symptoms were 9.9 (2.5), and the anxiety symptoms score was 12.6 (2.1). At 13 years, half of the patients (50.9%) had died. No significant effect of anxiety (p=0.399, 95% C.I.= 6.2-8.4) or depressive symptoms at inception (p=0.749, 95% C.I.= 5.9-8.4) towards cancer patients’ survival was found at 13 years follow-up. Conclusion: The occurrence of anxiety symptoms among cancer patients in this study was 2-folds higher than depressive symptoms. However, no significant increased risk of death was found in cancer patients with anxiety or depressive symptoms at 13 years follow-up. It may imply that as time extended, survival in cancer patients may be related to various interacting elements, and intervening health factors are of importance.

scholarly journals Drug therapy, potential interactions and iatrogenesis as factors related to frailty in the elderly

2018 ◽  
Vol 21 (5) ◽  
pp. 588-596 ◽  
Author(s):  
Andressa Rodrigues Pagno ◽  
Carolina Baldissera Gross ◽  
Daiana Meggiolaro Gewehr ◽  
Christiane de Fátima Colet ◽  
Evelise Moraes Berlezi
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
Inappropriate Medication ◽  
The Elderly ◽  
Potentially Inappropriate Medication ◽  
Potentially Inappropriate Medications ◽  
Elderly Persons ◽  
Potential Drug ◽  
Increased Risk ◽  
Inappropriate Medications

Abstract Objective: to investigate the use of drugs, potential drug interactions and iatrogenesis, as factors associated with frailty. Method: an observational, cross-sectional, population-based study of elderly persons registered with the Family Health Strategies of the urban area of a municipal region in the south of Brazil was carried out. The sample was probabilistic and involved 554 elderly persons; and the proportional stratified sampling technique by FHS and gender was used. Data collection was performed in the home, with the gathering of information regarding sociodemographic characteristics and pharmacotherapeutic profile and the evaluation of frailty based on Fried et al. (2001). Results: medications were taken by 86.3% of the elderly and there was a prevalence of frailty of 63.0%. A total of 39.4% of the elderly were exposed to polypharmacy, 49.1% used potentially inappropriate medications and 52.2% were exposed to potential drug interactions, the most frequent being enalapril and metformin. An association between increased risk of frailty and the variables: polypharmacy; use of potentially inappropriate medications; potential drug interactions; more than two potential drug interactions with the presence or absence of potentially inappropriate medication was identified. Conclusion: an association was found between frailty and polypharmacy, the use of potentially inappropriate medication and the presence of drug interactions. The findings underscore the importance of the monitoring of drug therapy in this population group with a view to the early detection, prevention and resolution of iatrogenesis arising from the use of medicines.

scholarly journals Lights and Shadows on Managing Immune Checkpoint Inhibitors in Oncology during the COVID-19 Era

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1906
Author(s):  
Chiara Burgaletto ◽  
Oronzo Brunetti ◽  
Antonio Munafò ◽  
Renato Bernardini ◽  
Nicola Silvestris ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Severe Disease ◽  
Inflammatory Phase ◽  
Clinical Observations ◽  
Increased Risk ◽  
The One

Since the start of the global spread of coronavirus disease (COVID-19) pandemic, cancer patients were identified as a specifically susceptible subgroup of the patient population. Several reports have shown that cancer patients have an increased risk of both contracting the infection and of experiencing a more severe disease course, with a rapidly evolving picture associated with higher mortality. The assumption of cancer patients as “COVID-19 vulnerable” has led, irretrievably, to profound changes in the decision making of oncological treatments. Potential justifications for such concerns encompass the cancer-dependent suppression of the immune response, as well as the influence of administration of systemic anticancer treatments, including chemotherapy and immunotherapy. Nevertheless, to date, it is not clear whether the use of immune checkpoint inhibitors (ICIs) in cancer patients is safe, given their modulating effects on the immune system, or that they may rather conceal detrimental consequences. Theoretically, on the one hand, ICIs may enhance the immunological control of viral infections through their immunostimulating mechanisms; on the other hand, they could contribute to the hyper-inflammatory phase of COVID-19, worsening its clinical outcomes. In this study, we report the foremost clinical observations on the safety of ICI administration in cancer patients affected by COVID-19.

scholarly journals A prospective cohort study on the safety of checkpoint inhibitors in older cancer patients – the ELDERS study

ESMO Open ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 100042
Author(s):  
F. Gomes ◽  
P. Lorigan ◽  
S. Woolley ◽  
P. Foden ◽  
K. Burns ◽  
...  
Keyword(s):  
Cohort Study ◽  
Cancer Patients ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Checkpoint Inhibitors ◽  
Older Cancer Patients

Efficacy of immune checkpoint inhibitors in cancer patients of different ages: a meta-analysis

2019 ◽  
Vol 15 (31) ◽  
pp. 3633-3646 ◽  
Author(s):  
Jing Li ◽  
Jian Gu
Keyword(s):  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Age Groups ◽  
Progression Free Survival ◽  
Systematic Evaluation ◽  
Free Survival ◽  
Older Cancer Patients

Aim: We conducted an up-to-date meta-analysis of randomized controlled trials (RCTs) to compare the immune checkpoint inhibitors (ICIs) in different age groups. Methods: The relevant RCTs in cancer patients receiving ICIs were searched and the systematic evaluation was performed. PubMed, MEDLINE and EMBASE were searched for studies published till January 2019. Results: A total of 27 RCTs included 17,546 patients were available for this meta-analysis. ICIs significantly improved overall survival (OS) and progression-free survival (PFS) in both of the younger (<65 years) and the older cancer patients (≥65 years). No significantly prolonged OS and PFS was observed among patients older than 75 years. Conclusion: ICIs could not significantly improve OS and PFS compared with controls in cancer patients aged over 75 years.

scholarly journals Cancer patients receiving immune checkpoint inhibitor therapy are at an increased risk for atherosclerotic cardiovascular disease

2020 ◽  
Vol 8 (1) ◽  
pp. e000300 ◽  
Author(s):  
Esther Lutgens ◽  
Tom T.P. Seijkens
Keyword(s):  
Cardiovascular Disease ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Inflammatory Diseases ◽  
Experimental Studies ◽  
Low Grade ◽  
Atherosclerotic Cardiovascular Disease ◽  
Increased Risk ◽  
Immune Checkpoint Proteins

The widespread clinical use of immune checkpoint inhibitors (ICI) has increased our knowledge on their adverse effects on chronic inflammatory diseases. Atherosclerosis, a low-grade lipid-driven inflammatory disease of the larger arteries, is commonly present in cancer patients. A major concern is the adverse effect of ICI on atherosclerosis-related cardiovascular disease, resulting in cardiovascular events, such as myocardial infarction or ischaemic stroke. The effects of ICI on atherosclerosis in cancer patients are incompletely understood, but it is well known that immune checkpoint proteins orchestrate the inflammatory response underlying atherogenesis. This paper addresses the hypothesis that ICI therapy puts cancer patients at an increased risk for atherosclerosis-related cardiovascular disease, that might only become apparent years after ICI therapy. Until clinical and experimental studies have addressed this hypothesis, optimal cardiovascular risk management in ICI-treated patients is opportune to reduce the occurrence of cardiovascular disease in cancer patients and long-term cancer survivors.

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