Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases

Eckmann, Karen R.; Michaud, Laura Boehnke; Rivera, Edgardo; Madden, Timothy; Esparza-Guerra, Laura; Kawedia, Jitesh D.; Booser, Daniel J.; Green, Marjorie C.; Hortobágyi, Gabriel N.; Valero, Vicente

doi:10.1177/1078155213480536

Cited by 14 publications

(14 citation statements)

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“…In a population PK analysis, patients with concomitant elevations of transaminases (ALT or AST > 1.5 × ULN) and alkaline phosphatase (>2.5 × ULN) showed a 27% reduction in docetaxel clearance and are higher risk of toxicity . However, in an observational study of docetaxel for patients with metastatic breast cancer and liver dysfunction, PK results suggested that docetaxel at 25 mg/m 2 for patients with more severe hepatic dysfunction (serum total bilirubin 1.5–3 × ULN, and ALT or ALT 2.5–5 × ULN) may be underdosed compared with docetaxel at 100 mg/m 2 for patients with normal hepatic functions . Docetaxel unbound clearance was lower and more variable in patients with hepatic dysfunction compared to those without hepatic dysfunction .…”

Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

2015

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Docetaxel (Taxotere®) has been one of the most important chemotherapeutic drugs for cancer treatment since 1996. Although a large number of clinical studies have been conducted in various cancer fields, there is a discrepancy in the standard dose between Japan and Western countries. This article reviews the pharmacokinetic, pharmacodynamic and toxicological profiles of docetaxel, and explains why there exists an ethnic difference in dose, and further discusses which direction we should go forward to solve this problem. The original recommended dose was 100 mg/m2 every 3 weeks in US and European populations, while a Japanese phase I study suggested the recommended dose as 60 mg/m2 every 3 weeks. A prospective population pharmacokinetic analysis of docetaxel conducted in both the USA/Europe and Japan, indicated an absence of ethnic difference in the pharmacokinetics. Both analyses demonstrated that docetaxel clearance is related to α1-acid glycoprotein level, hepatic function, age and body surface area. The relationship was observed between increasing docetaxel dose and increased tumor response rates across the dose range of 60 to 100 mg/m2. The area under the serum concentration time curve (AUC) of docetaxel at the first cycle was significantly related to time to progression. Hematological toxicities were well correlated with the AUC of docetaxel, and severe hematological toxicities were more frequently observed in Japanese patients treated with 60 mg/m2, compared to the US/European patients treated with 75–100 mg/m2 dose. The Japanese population seems more susceptible to the toxicity of docetaxel. A docetaxel dose of 75 mg/m2 is now standard not only in global trials but also in recent Japanese trials. Although the optimal dose of docetaxel is still unclear, we need to continue to seek the appropriate dose of docetaxel depending on patient status and the goals of chemotherapy.

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Section: Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

2015

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“…It has been reported that an average of 37% of obese patients undergoing bariatric surgery have NASH, which is higher than the rate observed in the general US adult population (Lazo and Clark, 2008). For both morphine and docetaxel, hepatic dysfunction is well documented to alter PK and requires dose-adjustment to avoid the occurrence of ADRs, potentially due to alteration in hepatic metabolism and transporter function (Bruno et al, 2001; Eckmann et al, 2014; Hasselström et al, 1990; Linares et al, 2009; Ozawa et al, 2008, 2009; Yoon et al, 2012). For docetaxel, several studies have attempted to assess whether doses should be adjusted based on various measures of obesity and body surface area (Griggs et al, 2012; Rudek et al, 2004; Sparreboom et al, 2007).…”

Section: Why Is Nash Currently Not Identified As a Key Player In Imentioning

confidence: 99%

Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability

Clarke

Cherrington

2015

Pharmacology & Therapeutics

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There are numerous factors in individual variability that make the development and implementation of precision medicine a challenge in the clinic. One of the main goals of precision medicine is to identify the correct dose for each individual in order to maximize therapeutic effect and minimize the occurrence of adverse drug reactions. Many promising advances have been made in identifying and understanding how factors such as genetic polymorphisms can influence drug pharmacokinetics (PK) and contribute to variable drug response (VDR), but it is clear that there remain many unidentified variables. Underlying liver diseases such as nonalcoholic steatohepatitis (NASH) alter absorption, distribution, metabolism, and excretion (ADME) processes and must be considered in the implementation of precision medicine. There is still a profound need for clinical investigation into how NASH-associated changes in ADME mediators, such as metabolism enzymes and transporters, affect the pharmacokinetics of individual drugs known to rely on these pathways for elimination. This review summarizes the key PK factors in individual variability and VDR and highlights NASH as an essential underlying factor that must be considered as the development of precision medicine advances. A multifactorial approach to precision medicine that considers the combination of two or more risk factors (e.g. genetics and NASH) will be required in our effort to provide a new era of benefit for patients.

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“…As first- or second-line chemotherapy, taxane agents including paclitaxel (taxol) and docetaxel (taxotere) are widely used in NSCLC. But they have different acute/subacute toxicity, which results in poor prognosis with only 15% of 5-years survival rate and substandard quality of life (QOL) [7, 8]. Therefore, new effective strategies with attenuation and synergistic efficacy are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Clinical Efficacy and Safety of Aidi Injection Plus Docetaxel‐Based Chemotherapy in Advanced Nonsmall Cell Lung Cancer: A Meta‐Analysis of 36 Randomized Controlled Trials

Xiao

Wang

Li³

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Background. Aidi injection is an important adjuvant anticancer drug commonly used in China. Can Aidi injection plus docetaxel-based chemotherapy improve clinical efficacy with good safety in NSCLC? To further reveal its clinical effectiveness, we systematically evaluated all the related studies. Method. We collected all the studies about Aidi injection plus docetaxel-based chemotherapy for NSCLC on Medline, Embase, Web of Science, CNKI, VIP, Wanfang, CBM, CENTRAL, Chi-CTR, and US-clinical trials. We evaluated their methodological bias risk according to the Cochrane evaluation handbook (5.1.0), extracted data following the predesigned data extraction form according to the PICO principle, and synthesized the data using meta-analysis. Results. We included 36 RCTs with 2837 patients, and most studies had unclear bias risk. The merged RR values and their 95% CI of meta-analysis for ORR, DCR, and QOL were as follows: 1.30 (1.19, 1.42), 1.17, (1.12, 1.22), and 1.73 (1.54, 1.95). The merged RR values for neutropenia, thrombocytopenia, anemia, gastrointestinal toxicity, hepatorenal dysfunctions, and alopecia were as follows: 0.70 (0.61, 0.79), 0.63 (0.53, 0.75), 0.60 (0.48, 0.75), 0.76 (0.65, 0.89), 0.56 (0.36, 0.88), and 0.58 (0.36, 0.93). Compared with chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that, with 100 ml, 80-100 ml, and 50 ml, Aidi injection could increase the tumor response and Aidi injection plus DP, DC, and DO could increase the tumor response. Meta-analysis results had good stability. Conclusions. Aidi injection plus docetaxel-based chemotherapy, especially plus DP, DC, and DO, may significantly improve the clinical efficacy and QOL in NSCLC. It may also have low risk of hematotoxicity, gastrointestinal toxicity, and low risk of inducing hepatorenal dysfunctions. Aidi injection may have attenuation and synergistic efficacy to docetaxel chemotherapy. All these need to have new evidence to be proved.

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Pilot study to assess toxicity and pharmacokinetics of docetaxel in patients with metastatic breast cancer and impaired liver function secondary to hepatic metastases

Abstract: Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.

Cited by 14 publications

References 18 publications

Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

Pharmacokinetics, dynamics and toxicity of docetaxel: Why the Japanese dose differs from the Western dose

Nonalcoholic steatohepatitis in precision medicine: Unraveling the factors that contribute to individual variability

Clinical Efficacy and Safety of Aidi Injection Plus Docetaxel‐Based Chemotherapy in Advanced Nonsmall Cell Lung Cancer: A Meta‐Analysis of 36 Randomized Controlled Trials

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