Treatments for chronic myeloid leukemia: a qualitative systematic review

Ferdinand, Roxanne; Mitchell, Stephen; Batson, Sarah; Tumur, Indra

doi:10.2147/jbm.s33380

Cited by 23 publications

(16 citation statements)

References 64 publications

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“…The success of cancer therapies in contributing to improved survival of cancer patients is due, in part, to the extensive use of combination drug therapy regimens and the limited but impressive effects of targeted mechanism-based therapies for treatment of some tumors. For example, the use of BCR-ABL tyrosine kinase inhibitors such as imatinib has increased the 5-year survival of chronic myeloid leukemia patients from 31% to 60% (Ferdinand et al 2012; Miller et al 2016). Unfortunately, “wonder” drugs for most other cancers have not been developed.…”

Section: Cancer Statistics and Backgroundmentioning

confidence: 99%

Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target

2017

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The aryl hydrocarbon receptor (AhR) was initially identified as the receptor that binds and mediates the toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and structurally related halogenated aromatics. Other toxic compounds including some polynuclear aromatic hydrocarbons act through the AhR; however, during the last 25 years, it has become apparent that the AhR plays an essential role in maintaining cellular homeostasis. Moreover, the scope of ligands that bind the AhR includes endogenous compounds such as multiple tryptophan metabolites, other endogenous biochemicals, pharmaceuticals and health-promoting phytochemicals including flavonoids, indole-3-carbinol and its metabolites. It has also been shown that like other receptors, the AhR is a drug target for multiple diseases including cancer, where both AhR agonists and antagonists effectively block many of the critical hallmarks of cancer in multiple tumor types. This review describes the anti-cancer activities of AhR ligands and demonstrates that it is time to separate the AhR from TCDD and exploit the potential of the AhR as a novel target for cancer chemotherapy.

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Section: Cancer Statistics and Backgroundmentioning

confidence: 99%

Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target

2017

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“…70 Simultaneously each agent targets tyrosine kinases within the cell uniquely to cause the desired anti-proliferative effect. Thus, although nilotinib and imatinib exhibit great selectivity for Bcr-Abl, stem cell factor (SCF) receptor (c-Kit), and platelet-derived growth factor receptors (PDGFR), these agents bind these kinases with different affinities.…”

Section: Overviewmentioning

confidence: 99%

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting

Cass

Connor

Tabachnik³

2016

J Oncol Pharm Pract

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Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted.

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“…An understanding of the divergent toxicity profiles associated with each of the currently approved TKIs, along with knowledge of patients' comorbidities and BCR-ABL mutational status, is critical to tailoring a particular TKI treatment to an individual patient (Cornelison, Jabbour, & Welch, 2012;Ferdinand, Mitchell, Batson, & Tumur, 2012;Wong & Mirshahidi, 2011). Although the mechanistic basis for many TKI-associated adverse events remains to be fully resolved, differences in toxicity profiles might reflect divergent specificities of the TKIs for BCR-ABL compared with other physiologically important kinases, including platelet-derived growth factor receptor (PDGF-R) and/or the c-kit proto-oncogene (Irvine & Williams, 2013;Jain et al, 2013;Puttini et al, 2006;Remsing Rix et al, 2009).…”

Section: Challenges Of Long-term Use Of Tkismentioning

confidence: 99%

Bosutinib Therapy in Patients With Chronic Myeloid Leukemia: Practical Considerations for Management of Side Effects

Ault¹,

Rose²,

Nodzon³

et al. 2016

JADPRO

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The past decade has witnessed great advances in the treatment of chronic myeloid leukemia (CML), brought about in large part by the development of BCR-ABL tyrosine kinase inhibitors (TKIs). Bosutinib joins the armamentarium of approved TKIs for the treatment of chronic phase (CP), accelerated phase (AP), and blast phase (BP) Philadelphia chromosome (Ph)-positive CML resistant to or intolerant of prior therapy. Bosutinib has an adverse-event (AE) profile distinct from that of other TKIs. Diarrhea is the predominant toxicity associated with bosutinib treatment; other commonly reported nonhematologic AEs include rash and liver enzyme elevations. Cardiac events, fluid retention, and electrolyte abnormalities are infrequent. Optimal response to bosutinib requires adherence, which depends, in part, upon optimal management of associated toxicities. The oncology clinician can facilitate this process by providing patient education, timely patient follow-up, and close monitoring to promptly identify and manage AEs. Thus, optimal patient management requires a thorough and current understanding of toxicity profiles and AE management paradigms. This review provides an overview of bosutinib safety data derived from ongoing clinical trials and offers practical clinical strategies currently used to manage toxicities associated with bosutinib treatment in patients with Ph-positive CP, AP, and BP CML.

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Treatments for chronic myeloid leukemia: a qualitative systematic review

Cited by 23 publications

References 64 publications

Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target

Role of the aryl hydrocarbon receptor in carcinogenesis and potential as an anti-cancer drug target

Safe handling of oral antineoplastic medications: Focus on targeted therapeutics in the home setting

Bosutinib Therapy in Patients With Chronic Myeloid Leukemia: Practical Considerations for Management of Side Effects

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