scholarly journals Long-Term Patterns of Oral Anticancer Agent Adoption, Duration, and Switching in Patients With CML

2019 ◽  
Vol 17 (10) ◽  
pp. 1166-1172 ◽  
Author(s):  
Matthew P. Banegas ◽  
Donna R. Rivera ◽  
Maureen C. O’Keeffe-Rosetti ◽  
Nikki M. Carroll ◽  
Pamala A. Pawloski ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Standard Of Care ◽  
Term Treatment ◽  
Oral Agent ◽  
Financial Outcomes ◽  
Long Term Treatment ◽  
Comorbidity Burden ◽  
Line Setting

Background: Oral tyrosine kinase inhibitors (TKIs) have been the standard of care for chronic myeloid leukemia (CML) since 2001. However, few studies have evaluated changes in the treatment landscape of CML over time. This study assessed the long-term treatment patterns of oral anticancer therapies among patients with CML. Methods: This retrospective cohort study included patients newly diagnosed with CML between January 1, 2000, and December 31, 2016, from 10 integrated healthcare systems. The proportion of patients treated with 5 FDA-approved oral TKI agents—bosutinib, dasatinib, imatinib, nilotinib, and ponatinib—in the 12 months after diagnosis were measured, overall and by year, between 2000 and 2017. We assessed the use of each oral agent through the fourth-line setting. Multivariable logistic regression estimated the odds of receiving any oral agent, adjusting for sociodemographic and clinical characteristics. Results: Among 853 patients with CML, 81% received an oral agent between 2000 and 2017. Use of non-oral therapies decreased from 100% in 2000 to 5% in 2005, coinciding with imatinib uptake from 65% in 2001 to 98% in 2005. Approximately 28% of patients switched to a second-line agent, 9% switched to a third-line agent, and 2% switched to a fourth-line agent. Adjusted analysis showed that age at diagnosis, year of diagnosis, and comorbidity burden were statistically significantly associated with odds of receiving an oral agent. Conclusions: A dramatic shift was seen in CML treatments away from traditional, nonoral chemotherapy toward use of novel oral TKIs between 2000 and 2017. As the costs of oral anticancer agents reach new highs, studies assessing the long-term health and financial outcomes among patients with CML are warranted.

Osteoporosis

2018 ◽  
Author(s):  
Angela J. Shepherd ◽  
Juliet M. Mckee
Keyword(s):  
Osteoporotic Fractures ◽  
Standard Of Care ◽  
Osteoporosis Treatment ◽  
Term Treatment ◽  
Osteoporosis Prevention ◽  
Vitamin Intake ◽  
Long Term Treatment ◽  
Good Nutrition ◽  
Moderate Alcohol Intake

Osteoporotic fractures are major causes of suffering and death. Dual-energy x-ray absorptiometry (DEXA) is the standard of care for diagnosis (T-score ≤ –2.5) of osteoporosis. Prevention of fractures requires addressing bone and muscle strength and balance. Physical exercise, good nutrition (fruits, vegetables, adequate calcium), adequate vitamin intake (C, D, and K), tobacco cessation, and no more than moderate alcohol intake enhance bone health and decrease fracture risk. Long-term treatment with glucocorticoids, certain drugs used in breast or prostate cancer treatment, and proton pump inhibitors used for gastroesophageal reflux disease may increase the risk for osteoporosis. Pharmacologically, bisphosphonates are the mainstay of osteoporosis treatment.

scholarly journals The Role of Rho Kinase in Sex-Dependent Vascular Dysfunction in Type 1 Diabetes

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Daniel W. Nuno ◽  
Kathryn G. Lamping
Keyword(s):  
Kinase Inhibitors ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Term Treatment ◽  
Compensatory Mechanisms ◽  
Rho Kinase Inhibitors ◽  
Long Term Treatment

We hypothesized that rho/rho kinase plays a role in sex differences in vascular dysfunction of diabetics. Contractions to serotonin were greater in isolated aortic rings from nondiabetic males versus females and increased further in streptozotocin-induced diabetic males but not females. The increased contractions to serotonin in males were reduced by inhibitors of rho kinase (fasudil, Y27632 and H1152) despite no change in expression of rhoA or rho kinase. Contractions to U46619 were not altered by fasudil or Y27632 or the presence of diabetes. In contrast to acute effects of fasudil, chronic treatment with fasudil increased contractions to serotonin in aorta from both non-diabetic and diabetic males. In summary, serotonin-induced contractions were increased in aorta from diabetic males but not females. Although administration of rho kinase inhibitors acutely decreased contractions to serotonin, long-term treatment with fasudil increased contractions. Long-term fasudil treatment may increase compensatory mechanisms to enhance vasoconstrictions.

scholarly journals BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia

2017 ◽  
Vol 24 (6) ◽  
pp. 433-452 ◽  
Author(s):  
Sandra Cuellar ◽  
Michael Vozniak ◽  
Jill Rhodes ◽  
Nicholas Forcello ◽  
Daniel Olszta
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Patient Centered ◽  
Long Term Treatment

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug–drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug–drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug–drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist–patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

VEGF kinase inhibitors: how do they cause hypertension?

2009 ◽  
Vol 297 (1) ◽  
pp. R1-R5 ◽  
Author(s):  
Pankaj Bhargava
Keyword(s):  
Kinase Inhibitors ◽  
Critical Phenomenon ◽  
Term Treatment ◽  
Vascular Endothelial ◽  
Preclinical Models ◽  
Long Term Treatment ◽  
Vegf Pathway ◽  
The Subject ◽  
Endothelial Growth Factor

Neoangiogenesis is a critical phenomenon enabling the growth and metastasis of tumors, and inhibitors of neoangiogenesis have been recently added to the armamentarium of anticancer therapies available for clinical use. Dysregulated signaling through the vascular endothelial growth factor (VEGF) pathway has been implicated as a key mediator of neoangiogenesis in tumors. Agents that block signaling through the VEGF pathway demonstrated tumor shrinkage in preclinical models and were therefore developed as anticancer therapies for use in humans. VEGF kinase inhibitors are being used in the treatment of a wide variety of cancers, and recent studies have shown that patients will likely require long-term treatment with these agents. Hypertension has emerged as a frequent side effect associated with agents that block signaling through the VEGF pathway. A thorough understanding of the mechanisms underlying hypertension is crucial to developing appropriate therapeutic strategies for treating hypertension associated with VEGF kinase inhibitors. Several recent studies have advanced our understanding of the pathophysiology of hypertension associated with VEGF kinase inhibitors and will be the subject of this review.

scholarly journals Shedding Light on Targeting Chronic Myeloid Leukemia Stem Cells

2021 ◽  
Vol 10 (24) ◽  
pp. 5805
Author(s):  
Mohammad Houshmand ◽  
Alireza Kazemi ◽  
Ali Anjam Najmedini ◽  
Muhammad Shahzad Ali ◽  
Valentina Gaidano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Term Treatment ◽  
Leukemia Stem Cells ◽  
Hematopoietic Stem ◽  
Long Term Treatment ◽  
Treatment Free Remission

Chronic myeloid leukemia stem cells (CML LSCs) are a rare and quiescent population that are resistant to tyrosine kinase inhibitors (TKI). When TKI therapy is discontinued in CML patients in deep, sustained and apparently stable molecular remission, these cells in approximately half of the cases restart to grow, resuming the leukemic process. The elimination of these TKI resistant leukemic stem cells is therefore an essential step in increasing the percentage of those patients who can reach a successful long-term treatment free remission (TFR). The understanding of the biology of the LSCs and the identification of the differences, phenotypic and/or metabolic, that could eventually allow them to be distinguished from the normal hematopoietic stem cells (HSCs) are therefore important steps in designing strategies to target LSCs in a rather selective way, sparing the normal counterparts.

scholarly journals Conversion from Positive to Negative EGFR Mutation due to Clonal Selection during Long-Term Treatment with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Case Report

2021 ◽  
Vol 14 (3) ◽  
pp. 1447-1453
Author(s):  
Masatomo Ueda ◽  
Masashi Namba ◽  
Kentaro Tokumo ◽  
Tadashi Senoo ◽  
Wataru Okamoto ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Pleural Effusion ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Epidermal Growth ◽  
L858r Mutation

A 77-year-old woman with postoperative recurrent non-small cell lung adenocarcinoma, which exhibited an <i>epidermal growth factor receptor (EGFR)</i> L858R mutation, was treated with gefitinib and erlotinib. Seven years after the start of treatment, the patient experienced a recurrence of malignant pleural effusion. However, 3 different genetic tests revealed that the lung adenocarcinoma cells in the pleural effusion had lost <i>EGFR</i> L858R mutation, suggesting that long-term treatment with EGFR-tyrosine kinase inhibitors (TKIs) converted <i>EGFR</i> mutation from positive to negative. The negative conversion of <i>EGFR</i> mutation as a mechanism of acquired resistance to EGFR-TKIs is considered rare and needs to be further investigated.

scholarly journals Inferring immunological control mechanisms from TKI dose alterations in CML patients

2019 ◽  
Author(s):  
Tom Hähnel ◽  
Christoph Baldow ◽  
Artur C. Fassoni ◽  
Joëlle Guilhot ◽  
François Guilhot ◽  
...  
Keyword(s):  
Immune Response ◽  
Kinase Inhibitors ◽  
Clinical Findings ◽  
Term Treatment ◽  
Control Mechanisms ◽  
Treatment Cessation ◽  
Long Term Treatment ◽  
Time Courses ◽  
The Individual

AbstractRecent clinical findings in chronic myeloid leukemia (CML) patients suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitors (TKI) treatment substantially depend on an individual, leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will most likely remain in a long-term treatment free remission (TFR). Here, we use a mathematical model for CML, which explicitly includes an anti-leukemic (presumably immunological) effect and apply it to a set of patients (n=60) for whom BCR-ABL/ABL time courses had been quantified before and after TKI stop. We demonstrate that such a feedback control is conceptually necessary to explain long-term remission as observed in about half of the patients. Based on simulation results we classify the patient data sets into three different groups according to their predicted immune system configuration. While one class of patients requires a complete CML eradication to achieve TFR, other patients are able to control the leukemia after treatment cessation. Among them, we identified a third class of patients, which only maintains TFR if an optimal balance between leukemia abundance and immunological activation is achieved before treatment cessation. Further, we demonstrate that the immune response classification of the patients cannot be obtained solely from BCR-ABL measurements before treatment cessation. However, our results strongly suggest that changes in the BCR-ABL dynamics arising after system perturbations, such as TKI dose reduction, holds the information to predict the individual outcome after treatment cessation.

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