Pharmacokinetics of vinorelbine in patients with liver metastases

Robieux, I.; Sorio, Roberto; Borsatti, Eugenio; Cannizzaro, Renato; Vitali, V.; Aita, P.; Freschi, Andrea; Galligioni, Enzo; Monfardini, S.

doi:10.1016/s0009-9236(96)90021-1

Cited by 69 publications

(34 citation statements)

References 22 publications

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“…Alteration in liver function related to either hepatic insufficiency or presence of liver metastases should impact the elimination of vinorelbine. No effect of liver metastases on vinorelbine clearance was found, which is in accordance with the finding of Robieux et al [21] with IV vinorelbine. They demonstrated that only a major invasion (more than 75%) of the liver by metastases can decrease the vinorelbine clearance.…”

Section: Discussionsupporting

confidence: 92%

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

Variol

Nguyen

Tranchand

et al. 2002

European Journal of Clinical Pharmacology

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By means of the simultaneous analysis of oral and intravenous data the bioavailability (F=36%) and its associated variability were estimated. At usual doses similar levels of variability were observed between oral and intravenous routes. As a result of the identification of covariates from phase I data and their confirmation from phase II data further explorations based on limited sampling strategies are now possible. The use of a simultaneous oral/intravenous model allows a better characterization of the PK profile of vinorelbine after administration by either vascular or oral route

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Section: Discussionsupporting

confidence: 92%

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

Variol

Nguyen

Tranchand

et al. 2002

European Journal of Clinical Pharmacology

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“…Although long-term survival can be achieved in some patients with limited hepatic disease [4], the prognosis for patients with disseminated liver metastases is commonly poor, and a median survival of 14 months after initial diagnosis of liver metastases can be expected [5,6]. Advanced liver metastases can cause hepatic dysfunction which is clinically apparent by hepatomegaly, jaundice, or the formation of ascites due to cholestasis and/or portal hypertension [7][8][9]. In general, liver metastases from breast cancer respond to chemotherapy [10], and anthracyclines and taxanes are still the most effective drugs for first-line treatment [11][12].…”

Section: Introductionmentioning

confidence: 99%

“…However, the efficacy of chemotherapy is frequently suboptimal as compared to other metastatic sites, as drug activity can be affected by impaired metabolic liver function [1]. Furthermore, hepatic dysfunction often limits the therapeutic options in these patients due to insufficient biliary drug clearing [8,9], and severe toxicity has been reported after administering standard dose regimens [13][14][15]. In particular, persisting hyperbilirubinemia with serum levels > 2 mg/dl precludes the use of most cytotoxic drugs [16,17].…”

Section: Introductionmentioning

confidence: 99%

Combined Chemotherapy with Mitomycin C, Folinic Acid, and 5-Fluorouracil (MiFoFU) as Salvage Treatment for Patients with Liver Metastases from Breast Cancer – a Retrospective Analysis

Eichbaum¹,

Gast²,

Brückner³

et al. 2008

Breast Care

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Background: The aim of this study was to analyze the activity and tolerability of a combined chemotherapy with mitomycin C, folinic acid, and 5-fluorouracil (MiFoFU) in patients with hepatic metastases from breast cancer, and in particular in patients with impaired liver function. Pa-tients and Methods: We retrospectively studied the charts of 44 patients who were treated with a MiFoFU combination therapy because of progressive metastatic breast cancer. Predominant site of metastases was the liver. Primary endpoints were response and time to progression (TTP); secondary endpoints were overall survival (OS) and tolerability. Results: Median age prior to treatment was 59 years. A median of 6 treatment cycles were administered per patient. Clinical benefit rate amounted to 64%. A mean TTP of 9 months and a mean OS of 14 months were found. Main clinical signs of nonhematological toxicity were stomatitis, nausea, and diarrhea. Grade III/IV hematotoxicity was seen in only 9 patients. 16 patients showed clinical signs of liver dysfunction. A clinical benefit could be achieved in 8 of these patients. Conclusions: MiFoFU combination chemotherapy is a well-tolerated treatment alternative in the palliative therapy of patients with liver metastases from breast cancer. Particularly in patients with hepatic dysfunction, this regimen seems to represent a helpful treatment option.

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“…Although a weak correlation exists between serum bilirubin level and vinorelbine clearance, current adjustments for this agent are based on serum bilirubin [29].…”

Section: Vinorelbinementioning

confidence: 99%

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

2007

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After completing this course, the reader will be able to:1. Describe the currently recommended dose adjustments for common chemotherapeutics in oncology patients with organ dysfunction.2. Explain the rationale for using phase I dose-escalation studies to determine appropriate chemotherapy dosing in patients with organ dysfunction.3. Discuss the limitations of the currently available studies to guide chemotherapy dose adjustment in patients with organ dysfunction.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThere are few prospective data regarding the pharmacokinetics and clinical toxicity of commonly used chemotherapeutics in cancer patients with organ dysfunction. Although increasing numbers of studies are investigating newer chemotherapeutics in patients with liver or kidney dysfunction, most guidelines for dosing, especially for established agents, remain empiric. This review describes the available data (both prospective and case study) evaluating the impact of renal and hepatic dysfunction on toxicity and dosing of commonly used chemotherapeutics and provides a practical summary for their use in this setting.

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Pharmacokinetics of vinorelbine in patients with liver metastases

Abstract: These results support vinorelbine dose reduction in patients with severe liver failure but not in patients with moderate secondary liver involvement. The monoethylglycinexylidide test may prove to be useful for vinorelbine dose individualization.

Cited by 69 publications

References 22 publications

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

Combined Chemotherapy with Mitomycin C, Folinic Acid, and 5-Fluorouracil (MiFoFU) as Salvage Treatment for Patients with Liver Metastases from Breast Cancer – a Retrospective Analysis

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

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Pharmacokinetics of vinorelbine in patients with liver metastases

Abstract: These results support vinorelbine dose reduction in patients with severe liver failure but not in patients with moderate secondary liver involvement. The monoethylglycinexylidide test may prove to be useful for vinorelbine dose individualization.

Cited by 69 publications

References 22 publications

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine

Combined Chemotherapy with Mitomycin C, Folinic Acid, and 5-Fluorouracil (MiFoFU) as Salvage Treatment for Patients with Liver Metastases from Breast Cancer &ndash; a Retrospective Analysis

Commentary: Oncologic Drugs in Patients with Organ Dysfunction: A Summary

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Combined Chemotherapy with Mitomycin C, Folinic Acid, and 5-Fluorouracil (MiFoFU) as Salvage Treatment for Patients with Liver Metastases from Breast Cancer – a Retrospective Analysis