Doxorubicin in Lymphoma: Association Between Pharmacokinetic Variability and Clinical Response

Elis, Avishay; Lishner, Michael; Walker, Scott; Atias, Dina; Korenberg, Avraham; Koren, Gideon

doi:10.1097/ftd.0b013e3181c3a16d

Cited by 12 publications

(10 citation statements)

References 7 publications

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“…Elis et al recently reported on the association between doxorubicin AUC and clinical response in 19 non-pregnant adult patients with Hodgkin’s lymphoma [38]. Using the same method to estimate the AUC in our subjects who were treated with short-term infusion, the values were within or greater than the range previously reported (274-742 ng•hr/mL).…”

Section: Discussionsupporting

confidence: 71%

Pharmacokinetics of doxorubicin in pregnant women

Ryu

Eyal

Kaplan

et al. 2014

Cancer Chemother Pharmacol

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Purpose Our objective was to evaluate the pharmacokinetics (PK) of doxorubicin during pregnancy compared to previously published data from non-pregnant subjects. Methods During mid- to late-pregnancy, serial blood and urine samples were collected over 72 hours from 7 women treated with doxorubicin for malignancies. PK parameters were estimated using noncompartmental techniques. Pregnancy parameters were compared to those previously reported non-pregnant subjects. Results During pregnancy, mean (± SD) doxorubicin PK parameters utilizing 72 hour sampling were: clearance (CL), 412 ± 80 mL/min/m2; steady-state volume of distribution (Vss), 1132 ± 476 L/m2; and terminal half-life (T1/2), 40.3 ± 8.9 hr. The BSA-adjusted CL was significantly decreased (p < 0.01) and T1/2 was not different compared to non-pregnant women. Truncating our data to 48 hours, PK parameters were: CL, 499 ± 116 ml/min/m2; Vss, 843 ± 391 L/m2; and T1/2, 24.8 ± 5.9 hr. The BSA-adjusted CL in pregnancy compared to non-pregnant data was significantly decreased in 2 of 3 non-pregnant studies (p < 0.05, < 0.05, NS). Vss and T1/2 were not significantly different. Conclusions In pregnant subjects, we observed significantly lower doxorubicin CL in our 72 hour and most of our 48 hour sampling comparisons with previously reported non-pregnant subjects. However, the parameters were within the range previously reported in smaller studies. At this time, we cannot recommend alternate dosage strategies for pregnant women. Further research is needed to understand the mechanism of doxorubicin pharmacokinetic changes during pregnancy and optimize care for pregnant women.

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Section: Discussionsupporting

confidence: 71%

Pharmacokinetics of doxorubicin in pregnant women

Ryu

Eyal

Kaplan

et al. 2014

Cancer Chemother Pharmacol

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“…They demonstrated that successful remission was associated with a higher median AUC. Those with median serum concentration of 280 ng/ml obtained successful remission compared with those who failed remission with median concentration of 73 ng/ml [145]. The authors concluded that TDM of doxorubicin may be warranted in patients with Hodgkins lymphoma, due to the wide variability observed in interindividual pharmacokinetics.…”

Section: Doxorubicinmentioning

confidence: 96%

“…There have been very few studies of the relationship between doxorubicin pharmacokinetics and clinical response. A recent study of doxorubicin by Elis et al studied the association of doxorubicin pharmacokinetics with remission rates in Hodgkins lymphoma patients [145]. They demonstrated that successful remission was associated with a higher median AUC.…”

Section: Doxorubicinmentioning

confidence: 98%

Therapeutic Drug Monitoring in Cancer Chemotherapy

Bach

Straseski

Clarke³

2010

Bioanalysis

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For a select number of drugs, proper management of patients includes monitoring serum or plasma concentrations of the drugs and adjusting the doses accordingly - this practice is referred to as therapeutic drug monitoring (TDM). The need for TDM arises when pharmacokinetic variability of drugs is not easily accounted for by common clinical parameters. Many chemotherapeutic drugs have large interindividual variability, yet TDM is not commonplace in chemotherapy management. This review will discuss pharmacokinetics in the context of chemotherapeutic drugs, examine the few instances where TDM is currently used in the field of oncology and propose other drugs where TDM might be useful for dose adjustments in the management of chemotherapy.

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“…Many factors such as patient demographics (age, gender, and body surface area), genetics, and the environment are known to alter the PK of a drug. Hence, these factors serve as potential causes of the inter-patient PK and PD variability associated with anticancer agents [1, 6, 7]. …”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

Schell

Sidone

Caron

et al. 2014

Nanomedicine: Nanotechnology, Biology and Medicine

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Purpose A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Methods Inter-patient PK variability of 9 liposomal and SM formulations of the same drug were evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). Results CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R2 = 0.39). PK variability of liposomal agents was greater when evaluated from 0–336 h compared with 0–24 h. Conclusion PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents needs to be evaluated.

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Doxorubicin in Lymphoma: Association Between Pharmacokinetic Variability and Clinical Response

Cited by 12 publications

References 7 publications

Pharmacokinetics of doxorubicin in pregnant women

Pharmacokinetics of doxorubicin in pregnant women

Therapeutic Drug Monitoring in Cancer Chemotherapy

Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents

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