Five-Year Survival in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma Treated With Axitinib

New anti-cancer drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway are highly effective in the treatment of solid tumors, however concerns remain regarding their cardiovascular safety. The most common side effect of VEGF signaling pathway (VSP) inhibition is the development of systemic hypertension. We review the incidence, possible mechanisms, significance and management of hypertension in patients treated with VSP inhibitors.

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“…The incidence rate of high-grade hypertension incidence was 13.5 %, similar to that shown in short-term studies [59].…”

Section: Axitinibsupporting

confidence: 71%

Hypertension in cancer patients treated with anti-angiogenic based regimens

et al. 2015

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“…[27] 2.2 Post-cytokine therapy Cytokines are no longer considered the standard of care as first-line mRCC therapy; however, the efficacy of TKI therapies axitinib, sorafenib, pazopanib and sunitinib in patients with cytokine-refractory mRCC has been demonstrated in various studies. [32][33][34][35][36] 2.3 Treatment strategies beyond first line: 'real-world' retrospective analyses…”

Section: Expert Opinionmentioning

confidence: 99%

Pharmacoeconomic and clinical implications of sequential therapy for metastatic renal cell carcinoma patients in Central and Eastern Europe

Vrdoljak

Torday

Szczylik

et al. 2015

Expert Opinion on Pharmacotherapy

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Introduction:The incidence and mortality rates of kidney cancer in the Central and Eastern European (CEE) region are among the highest in the world. Access to second and subsequent lines of metastatic renal cell carcinoma (mRCC) therapies is highly varied in the region. Despite the increasing body of evidence supporting the clinical benefit of multiple lines of treatment, access to treatment beyond first line is restricted in many of these countries. Areas covered: The adoption of targeted therapies for the first-line treatment of mRCC in the region was slow and faced many obstacles. In order to evaluate the current status of treatment beyond the first-line setting in the CEE region, this review examines the availability and reimbursement of mRCC drugs and clinical practice in institutions that treat patients with mRCC. Expert opinion: This review highlights the need to raise awareness among physicians, payers and regulators on clinical trial and cost-effectiveness data regarding the treatment of mRCC beyond the first line. The obstacles to mRCC drug access highlighted in this review need to be overcome to ensure that patients are receiving the best treatment available.

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“…74 Other work has demonstrated an exposure-response relationship, with a clear relationship now being established between AUC and survival. [75][76][77] In addition to AUC, change in diastolic blood pressure (DBP) has become an established pharmacodynamic surrogate for axitinib efficacy. [77][78][79][80] Although DBP may show considerable intrapatient variability, the possibility of dose titration based on exposure has not been confirmed, and hence until PK targets are identified, dosing based on DBP is probably a better axitinib dose-individualization strategy than TDM, at least in renal cell cancer patients.…”

Section: Additional Tkis Potentially Feasible For Tdmmentioning

confidence: 99%

Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents

Lucas

Martin

2017

The Journal of Clinical Pharma

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Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese-even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area-guided dosing, therapeutic drug monitoring or pharmacokinetic-guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size-based dosing or "one dose fits all" is used. This review will focus predominantly on the rationale for pharmacokinetic-guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.

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Five-Year Survival in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma Treated With Axitinib

Cited by 45 publications

References 28 publications

Hypertension in cancer patients treated with anti-angiogenic based regimens

Hypertension in cancer patients treated with anti-angiogenic based regimens

Pharmacoeconomic and clinical implications of sequential therapy for metastatic renal cell carcinoma patients in Central and Eastern Europe

Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents

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