A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model

Quartino, Angelica; Friberg, Lena E.; Karlsson, Mats O.

doi:10.1007/s10637-010-9603-3

Cited by 54 publications

(44 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current model assumes a steady state; application to non-steady-state situations such as trauma and sepsis may be attained by the inclusion of a feedback loop affecting proliferation, as has been done before in studies of myelosuppression upon antitumor treatment. 45,51,52 Similarly, circadian oscillations are not included within the steady-state model. Blood neutrophil counts follow a circadian rhythm, 53,54 which may be due to changes in proliferation, transit/release, or death/disappearance.…”

Section: Discussionmentioning

confidence: 99%

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives

Lahoz-Beneytez

Elemans

Zhang

et al. 2016

Blood

228

234

View full text Add to dashboard Cite

Human neutrophils have traditionally been thought to have a short half-life in blood; estimates vary from 4 to 18 hours. This dogma was recently challenged by stable isotope labeling studies with heavy water, which yielded estimates in excess of 3 days. To investigate this disparity, we generated new stable isotope labeling data in healthy adult subjects using both heavy water (n = 4) and deuterium-labeled glucose (n = 9), a compound with more rapid labeling kinetics. To interpret results, we developed a novel mechanistic model and applied it to previously published (n = 5) and newly generated data. We initially constrained the ratio of the blood neutrophil pool to the marrow precursor pool (ratio = 0.26; from published values). Analysis of heavy water data sets yielded turnover rates consistent with a short blood half-life, but parameters, particularly marrow transit time, were poorly defined. Analysis of glucose-labeling data yielded more precise estimates of half-life (0.79 ± 0.25 days; 19 hours) and marrow transit time (5.80 ± 0.42 days). Substitution of this marrow transit time in the heavy water analysis gave a better-defined blood half-life of 0.77 ± 0.14 days (18.5 hours), close to glucose-derived values. Allowing the ratio of blood neutrophils to mitotic neutrophil precursors (R) to vary yielded a best-fit value of 0.19. Reanalysis of the previously published model and data also revealed the origin of their long estimates for neutrophil half-life: an implicit assumption that R is very large, which is physiologically untenable. We conclude that stable isotope labeling in healthy humans is consistent with a blood neutrophil half-life of less than 1 day.

show abstract

Section: Discussionmentioning

confidence: 99%

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives

Lahoz-Beneytez

Elemans

Zhang

et al. 2016

Blood

228

234

View full text Add to dashboard Cite

show abstract

“…Docetaxel is known to induce myelosuppression and reduce WBC counts in a time and dose-dependent fashion (7,8,40) and data from this study suggest that PSK may mitigate these effects while enhancing antitumor responses. With respect to direct immunological effects, docetaxel treatment in mice bearing syngeneic transplanted tumors induced a significant increase in T cell and NK cell infiltration into tumors (41).…”

Section: Discussionmentioning

confidence: 68%

“…Docetaxel acts by stabilizing microtubules in mitotic spindles, directly inhibiting the cell division process (5,6). Because docetaxel is cytotoxic to all dividing cells, it induces myelosuppression and neutropenia at therapeutic doses (7,8), limiting its therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer

Wenner

Martzen²,

Lu³

et al. 2011

International Journal of Oncology

View full text Add to dashboard Cite

Advanced castration-resistant prostate cancer has high mortality rates and limited treatment options. Novel therapies are needed to better contend with this disease. Polysaccharide-K® (PSK), an extract of the mushroom Trametes versicolor, has immunomodulatory and tumor suppressive activities. PSK is used in Asia as a cancer immunotherapy. However, its benefit in combination with taxanes for prostate cancer is unknown. We examined whether PSK would enhance docetaxel-induced apoptosis and augment anti-tumor immune responses in orthotopic tumors using transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2-bearing mice. Combining PSK with docetaxel induced significantly higher tumor suppression than either treatment alone (p<0.05), including a reduction in tumor proliferation and enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease in number of white blood cells than docetaxel alone, an effect accompanied by increased numbers of tumor-infiltrating CD4+ and CD8+ T cells. PSK with or without docetaxel significantly enhanced mRNA expression of IFN-γ compared to control, but did not significantly alter T-regulatory FoxP3 mRNA expression in tumors. PSK also augmented docetaxel-induced splenic natural killer cell cytolytic activity against YAC-1 target cells (p=0.045). This study is the first to show that PSK enhances docetaxel-induced prostate cancer tumor suppression, apoptosis and antitumor responses.

show abstract

“…The ANC dynamics component of the model was represented by a catenary chain of four compartments to mimic the production and maturation of neutrophils in the bone marrow . The receptors were tracked through the production, maturation and turnover of neutrophils, which were represented by stem cells ( R SM ), cells undergoing mitosis ( R MT ) and the two precursor states in the bone marrow ( R PM 1 and R PM 2 ).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic–pharmacodynamic modelling of neutrophil response to G‐CSF in healthy subjects and patients with chemotherapy‐induced neutropenia

Melhem

Delor²,

Pérez-Ruixo³

et al. 2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model

Cited by 54 publications

References 39 publications

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives

Human neutrophil kinetics: modeling of stable isotope labeling data supports short blood neutrophil half-lives

Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer

Pharmacokinetic–pharmacodynamic modelling of neutrophil response to G‐CSF in healthy subjects and patients with chemotherapy‐induced neutropenia

Contact Info

Product

Resources

About