Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma

Lyass, Olga; Uziely, Beatrice; Ben‐Yosef, Rami; Tzemach, Dinah; Heshing, Norman I.; Lotem, Michal; Brufman, G; Gabizón, Alberto

doi:10.1002/1097-0142(20000901)89:5<1037::aid-cncr13>3.0.co;2-z

Cited by 348 publications

(173 citation statements)

References 28 publications

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“…However, the incidence of marked skin toxicity observed in our study, is significantly lower than that usually reported when lower doses of PLD (35 mg m À2 ) are administered in shorter time intervals, every 3 weeks (Gogas et al, 2002). The addition of paclitaxel to the higher dose of PLD used in our study did not seem to affect the incidence of skin toxicity, as this is possibly related to the dose scheduling intervals and exposure to persistent drug levels (Lyass et al, 2000). There was no apparent cardiac toxicity observed in our cohort of patients.…”

Section: Discussioncontrasting

confidence: 78%

Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group

et al. 2004

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Patients with soft tissue sarcoma (STS), even after complete local disease control, often relapse locally or with distant metastases. This multicenter phase II study was conducted to evaluate the safety and efficacy of the combination of pegylated liposomal doxorubicin (PLD) and paclitaxel, as first-line treatment in patients with advanced STS. In all, 42 patients with locally advanced or metastatic STS, median age 54 years and median Eastern Cooperative Oncology Group performance status (PS) 1 were treated with PLD 45 mg m À2 and paclitaxel 150 mg m À2 , every 28 days for a total of six cycles. Histological types included mainly leiomyosarcomas (43%), malignant fibrous histiocytomas (14%) and liposarcomas (12%). At study entry, 69% of patients had distant metastases. Overall response rate was 16%, including one complete (CR 2%) and six partial responses (PRs 14%), while an additional 14 patients had disease stabilization (SD 33%). At median follow-up 41.5 months, median time to progression (TTP) was 5.7 months with median overall survival (OS) 13.2 months. Grade 3 -4 toxicities included neutropenia (17%), anaemia (15%), neurotoxicity (5%) and palmarplantar erythrodysesthesia (9%). There were no treatment-related deaths. The combination of PLD and paclitaxel is a safe and welltolerated regimen demonstrating modest efficacy as first-line treatment in patients with advanced STS.

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Section: Discussioncontrasting

confidence: 78%

Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group

et al. 2004

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“…For chemotherapy, the liposome vesicle can accumulate higher concentration/percentage of drug in tumor (increase therapeutic index), and prevent the drug (toxic agent) exposed to the normal tissue and causing damage during transportation or been sabotaged before arriving target tumor site (reduce side effects). The liposome delivered anticancer agents, such as doxorubicin, have been proved to reduce side effects (cardio-toxicity, hear loss……) while exhibiting superior performance or preserving efficacy in clinical studies with maintaining extended period of above threshold value concentration for treatment [9]- [11]. Considerable efforts have been devoted for the lifetime and integrity of liposomes in the bloodstream for hours to days, increasing the successful rate of transportation to the target location [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Prevention of Contrast Medium Induced Nephropathy by Liposome Encapsulation

Lee¹,

Chai²,

Hu³

et al. 2013

IJBBB

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“…Among other potential determinants, PI plasma levels have been less studied although the measurement of drug concentration, i.e. therapeutic drug monitoring (TDM), has shown a large interest in many diseases (3)(4)(5), to improve efficacy and minimize toxicity. Moreover, PIs are good candidates for TDM because of high inter-patient variability in plasma concentrations, binding to plasma proteins, P450 3A4 cytochrom metabolism, short half-life, drug-food and drug-drug interactions (6,7) that may lead to inadequate PIs exposure among patients receiving the same dose.…”

Section: Introductionmentioning

confidence: 99%

Indinavir Trough Concentration as a Determinant of Early Nephrolithiasis in HIV-1-Infected Adults

Collin

Chêne²,

Retout³

et al. 2007

Therapeutic Drug Monitoring

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Indinavir plasma levels are associated with antiretroviral efficacy however few data is available regarding toxicity. We assessed the relationship between indinavir pharmacokinetic (PK) characteristics and severe nephrolithiasis as well as other severe or serious adverse reactions (SAR). Patients included in the ANRS CO8 APROCO-COPILOTE cohort and receiving indinavir 800 mg thrice daily as first line protease inhibitor, were eligible for this study. To be included in the analysis, their plasma sample at month 1 (M1) had to be available (n=282) to estimate, using population PK modelling, indinavir PK characteristics, i.e. maximum (C max ) and trough plasma (C res ) concentrations, area under the curve (AUC) and observed/predicted concentrations ratio (CR). A Cox model was used to estimate the independent effect of C max , C res , AUC and CR on the hazard of severe nephrolithiasis and SAR. At M1, median C max was 6 205 ng/mL, C res : 631 ng/mL, AUC: 24 242 ng.h/mL and CR: 0.6. After a median follow-up of 12 months, 11% of patients (30/282) had experienced at least one SAR among which 12 were nephrolithiasis.In the multivariate analyses, early high indinavir C res (i.e. ≥ 1000 ng/mL at M1) was associated with a higher rate of severe nephrolithiasis (HR=6.7; 95% confidence interval=1.8-25.2; p<0.01) and was also associated with a higher rate of all SAR but only when nephrolithiasis were included among those cases. Prospective and early indinavir C res determination should be recommended in the patient's care management and dosage adjustments.

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Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma

Cited by 348 publications

References 28 publications

Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group

Combination of pegylated liposomal doxorubicin (PLD) and paclitaxel in patients with advanced soft tissue sarcoma: a phase II study of the Hellenic Cooperative Oncology Group

Prevention of Contrast Medium Induced Nephropathy by Liposome Encapsulation

Indinavir Trough Concentration as a Determinant of Early Nephrolithiasis in HIV-1-Infected Adults

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