Prospective Evaluation of the Relationship of Patient Age and Paclitaxel Clinical Pharmacology: Cancer and Leukemia Group B (CALGB 9762)

Lichtman, Stuart M.; Hollis, Donna; Miller, Antonius A.; Rosner, Gary L.; Rhoades, Chris A.; Lester, Eric P.; Millard, Frederick E.; Byrd, John C.; Cullinan, Stephen A.; Rosen, David; Parise, Robert A.; Ratain, Mark J.; Egorin, Merrill J.

doi:10.1200/jco.2005.03.9289

Cited by 86 publications

(57 citation statements)

References 32 publications

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“…A prospective trial by the Cancer and Leukemia Group B (CALGB 9762) demonstrated age-related differences in the pharmacokinetics of paclitaxel but no significant adverse sequelae in terms of infections and hospitalization. However, this trial analysed only the first cycle of treatment and cumulative toxicity was not assessed [Lichtman et al 2006]. An increased cardiovascular toxicity was reported in a prospective study of qw paclitaxel in 46 elderly patients with MBC; the baseline geriatric assessment predicted a lower probability of response and survival but not of toxicity [Del Mastro et al 2005].…”

Section: Elderly Patients With Metastatic Breast Cancermentioning

confidence: 99%

Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients?

2016

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Abstract:The therapeutic goals in metastatic breast cancer (MBC) remain palliative in nature, aimed at controlling symptoms, improving or maintaining quality of life and prolonging survival. The advent of new drugs and new formulations of standard agents has led to better outcomes in patients with advanced or metastatic disease. These developments have also allowed a tailored therapeutic approach, in which the molecular biology of the tumour, the treatment history, and patient attitudes are taken into account in the decision-making process. Targeting drug delivery to the tumour is a promising mean of increasing the therapeutic index of highly active agents such as the taxanes, and nanoparticle albuminbound paclitaxel (nab-paclitaxel), the first nanotechnology-based drug developed in cancer treatment, is one such advance. Data from randomized trials support the efficacy of singleagent nab-paclitaxel as first-line and further treatment lines in MBC at the registered 3-weekly schedule of 260 mg/m 2 , but emerging evidence suggests its activity as a weekly regimen or combined with other agents in various clinical scenarios. Thus, nab-paclitaxel seems to offer flexibility in terms of dosing schedules, allowing physicians to tailor the dose according to different clinical situations. This paper reviews the clinical trial background for nab-paclitaxel in MBC, focusing on specific 'difficult-to-treat' patient populations, such as taxane-pretreated or elderly women, as well as those with triple-negative, HER2-positive and poor-prognosticfactors disease. Moving beyond evidence-based information, 'real life' available experiences are also discussed with the aim of providing an update for daily clinical practice.

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Section: Elderly Patients With Metastatic Breast Cancermentioning

confidence: 99%

Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients?

2016

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“…The potential of natural products from plants, notably from traditional Chinese medicine (TCM), has been recognized by the scientific community in the Western world for its low toxicity, and considerable efforts have been made to systematically investigate the active component of TCM for cancer therapy. A series of natural products, such as Homoharringtonine (6), arsenic trioxide (ATO) (7) and paclitaxel (8), have been found and clinically proved for their potential use in leukemia therapy. They demonstrate the translation of basic knowledge of purified agents of complex mixtures from TCM into the clinic.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells

Ren

Zhang

et al. 2013

Oncology Reports

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Abstract. Hexamethylene bisacetamide (HMBA) and natural flavanoid baicalin both exert potent antileukemic activity. However, there is currently no data on the anti-leukemic effects of baicalin in combination with HMBA. In the present study, we demonstrated that the combination of baicalin and HMBA synergistically inhibited the proliferation of acute myeloid leukemia (AML) cell lines. In addition, a slight G 0 /G 1 phase arrest and significant apoptosis were observed. The combination treatment triggered apoptosis through the intrinsic pathway, which involved loss of MMP, decreased Bcl-2/Bax ratio and Bcl-X L /Bax ratio, caspase-9 activation, as well as through the extrinsic pathway mediated by Fas and caspase-8 activation. On the other hand, combination of baicalin and HMBA showed little toxic effect on peripheral blood mononuclear cells from healthy volunteers. Our results raise the possibility that the novel combination of baicalin and HMBA may be a promising regimen for the treatment of AML.

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“…With higher age, there was an increase in the area under the curve (AUC) of paclitaxel and a decrease in drug clearance. This translated into an age-related increase in grade 3 neutropenia and lower absolute neutrophil count (ANC) nadir; however, there was no increase in the incidence of fever, hospitalisation, or need for intravenous antibiotics (Lichtman et al, 2006). Common comorbid medical conditions in older adults may impact tolerance to cancer therapy.…”

Section: Taxanesmentioning

confidence: 99%

Clinical pharmacology of cancer therapies in older adults

Hurria

Lichtman

2008

Br J Cancer

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This abbreviated review outlines the physiologic changes associated with aging, and examines how these changes may affect the pharmacokinetics and pharmacodynamics of anticancer therapies. We also provide an overview of studies that have been conducted evaluating the pharmacology of anticancer therapies in older adults, and issue a call for further research. (Yancik and Ries, 2000). As the general population ages and life expectancy increases, the number of older adults with cancer is growing.Several unique challenges arise in caring for older adults with cancer. In particular, the physiologic changes associated with aging can have an impact on the pharmacokinetics and pharmacodynamics of cancer therapies. The effects of these age-related changes on drug dosing and tolerance have been understudied, as clinical trials that set the standards for oncology care and drug approval have typically focused on a younger patient population (Hutchins et al, 1999;Talarico et al, 2004). Few studies have included patients who are frail or who have a poor performance status (Table 1).In this review, we provide an overview of the physiologic changes that accompany aging that may have an impact on the pharmacology of anticancer therapies. We also discuss recent studies evaluating the pharmacology of anticancer therapies in older adults. PHYSIOLOGIC CHANGES WITH AGINGAging is a heterogenous process; however, some characteristic changes in physiology and organ function can have an impact on the pharmacology of anticancer therapy. For example, age-related changes in the gastrointestinal tract may affect drug absorption. These changes include a decrease in splanchnic blood flow, gastrointestinal motility, secretion of digestive enzymes, and mucosal atrophy (Yuen, 1990;Baker and Grochow, 1997). With increasing age, hepatic mass decreases and there is a decrease in the cytochrome p450 content in liver biopsies, although the impact of these declines on hepatic function remains controversial (Sotaniemi et al, 1997;Shah, 2004;Sawhney et al, 2005).There is a decrease in renal mass and renal blood flow with aging (Vestal, 1997). These age-related changes in renal function could affect the pharmacology of anticancer drugs. A serum creatinine is often used to approximate renal function in younger adults; however, it is a poor indicator of renal function in older adults because of a decrease in muscle mass with age (FehrmanEkholm and Skeppholm, 2004). On average, the glomerular filtration rate decreases by approximately 0.75 ml min À1 year À1

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Prospective Evaluation of the Relationship of Patient Age and Paclitaxel Clinical Pharmacology: Cancer and Leukemia Group B (CALGB 9762)

Abstract: Although paclitaxel CL(tb) decreases with increasing patient age, there is great interpatient variability. Cooperative group studies to evaluate the effect of aging on pharmacokinetics are feasible.

Cited by 86 publications

References 32 publications

Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients?

Targeted chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in metastatic breast cancer: which benefit for which patients?

Enhancement of baicalin by hexamethylene bisacetamide on the induction of apoptosis contributes to simultaneous activation of the intrinsic and extrinsic apoptotic pathways in human leukemia cells

Clinical pharmacology of cancer therapies in older adults

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