Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi's sarcoma: An Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial

Mary Cianfrocca, Sandra Lee, Jamie Von Roenn, Michelle A. Rudek, Bruce J. Dezube, Susan E. Krown, Joseph A. Sparano

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Abstract

Purpose: Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel. Methods: Patients with advanced HIV-associated KS received paclitaxel (100 mg/m 2) by intravenous infusion over 3 h, and plasma samples were collected to measure paclitaxel concentration. The area under the curve (AUC) was calculated using a combination of the log and linear trapezoidal rule, and clearance was calculated as the dose/AUC. Pharmacokinetics were compared with respect to antiretroviral therapy and toxicity, Results: Thirty-four patients received paclitaxel, of whom 20 had no prior paclitaxel therapy and were assessable for response. Twenty-seven had pharmacokinetic studies performed. Paclitaxel exposure was higher in patients taking protease inhibitors compared to those who were not taking protease inhibitors. The increased exposure did not correlate with efficacy or toxicity. Of the 20 patients assessable for response, 6 (30%) had an objective response and median progression-free survival was 7.8 months (95% confidence interval, 5.6, 21.0 months). Conclusion: Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy.

Original languageEnglish (US)
Pages (from-to)827-833
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume68
Issue number4
DOIs
StatePublished - Oct 2011

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Oncology
Kaposi's Sarcoma
Paclitaxel
Protease Inhibitors
Viruses
Acquired Immunodeficiency Syndrome
HIV
Pharmacokinetics
Neoplasms
Cytochrome P-450 Enzyme System
Toxicity
Area Under Curve
Cytotoxins
Intravenous Infusions
Disease-Free Survival
HIV Infections
Therapeutics
Confidence Intervals
Plasmas
Liver

Keywords

  • AIDS
  • HIV infection
  • Kaposi's sarcoma
  • Paclitaxel
  • Protease inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

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title = "Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi's sarcoma: An Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial",
abstract = "Purpose: Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel. Methods: Patients with advanced HIV-associated KS received paclitaxel (100 mg/m 2) by intravenous infusion over 3 h, and plasma samples were collected to measure paclitaxel concentration. The area under the curve (AUC) was calculated using a combination of the log and linear trapezoidal rule, and clearance was calculated as the dose/AUC. Pharmacokinetics were compared with respect to antiretroviral therapy and toxicity, Results: Thirty-four patients received paclitaxel, of whom 20 had no prior paclitaxel therapy and were assessable for response. Twenty-seven had pharmacokinetic studies performed. Paclitaxel exposure was higher in patients taking protease inhibitors compared to those who were not taking protease inhibitors. The increased exposure did not correlate with efficacy or toxicity. Of the 20 patients assessable for response, 6 (30{\%}) had an objective response and median progression-free survival was 7.8 months (95{\%} confidence interval, 5.6, 21.0 months). Conclusion: Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy.",
keywords = "AIDS, HIV infection, Kaposi's sarcoma, Paclitaxel, Protease inhibitors",
author = "Mary Cianfrocca and Sandra Lee and {Von Roenn}, Jamie and Rudek, {Michelle A.} and Dezube, {Bruce J.} and Krown, {Susan E.} and Sparano, {Joseph A.}",
year = "2011",
month = "10",
doi = "10.1007/s00280-010-1509-4",
language = "English (US)",
volume = "68",
pages = "827--833",
journal = "Cancer Chemotherapy and Pharmacology",
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}

TY - JOUR

T1 - Pilot study evaluating the interaction between paclitaxel and protease inhibitors in patients with human immunodeficiency virus-associated Kaposi's sarcoma

T2 - An Eastern Cooperative Oncology Group (ECOG) and AIDS Malignancy Consortium (AMC) trial

AU - Cianfrocca, Mary

AU - Lee, Sandra

AU - Von Roenn, Jamie

AU - Rudek, Michelle A.

AU - Dezube, Bruce J.

AU - Krown, Susan E.

AU - Sparano, Joseph A.

PY - 2011/10

Y1 - 2011/10

N2 - Purpose: Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel. Methods: Patients with advanced HIV-associated KS received paclitaxel (100 mg/m 2) by intravenous infusion over 3 h, and plasma samples were collected to measure paclitaxel concentration. The area under the curve (AUC) was calculated using a combination of the log and linear trapezoidal rule, and clearance was calculated as the dose/AUC. Pharmacokinetics were compared with respect to antiretroviral therapy and toxicity, Results: Thirty-four patients received paclitaxel, of whom 20 had no prior paclitaxel therapy and were assessable for response. Twenty-seven had pharmacokinetic studies performed. Paclitaxel exposure was higher in patients taking protease inhibitors compared to those who were not taking protease inhibitors. The increased exposure did not correlate with efficacy or toxicity. Of the 20 patients assessable for response, 6 (30%) had an objective response and median progression-free survival was 7.8 months (95% confidence interval, 5.6, 21.0 months). Conclusion: Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy.

AB - Purpose: Paclitaxel, a cytotoxic agent metabolized by cytochrome P450 hepatic enzymes, is active for the treatment of human immunodeficiency (HIV) associated Kaposi's sarcoma. Protease inhibitors are commonly used to treat HIV infection and are known to inhibit cytochrome P450. We sought to determine whether protease inhibitors alter the pharmacokinetics of paclitaxel. Methods: Patients with advanced HIV-associated KS received paclitaxel (100 mg/m 2) by intravenous infusion over 3 h, and plasma samples were collected to measure paclitaxel concentration. The area under the curve (AUC) was calculated using a combination of the log and linear trapezoidal rule, and clearance was calculated as the dose/AUC. Pharmacokinetics were compared with respect to antiretroviral therapy and toxicity, Results: Thirty-four patients received paclitaxel, of whom 20 had no prior paclitaxel therapy and were assessable for response. Twenty-seven had pharmacokinetic studies performed. Paclitaxel exposure was higher in patients taking protease inhibitors compared to those who were not taking protease inhibitors. The increased exposure did not correlate with efficacy or toxicity. Of the 20 patients assessable for response, 6 (30%) had an objective response and median progression-free survival was 7.8 months (95% confidence interval, 5.6, 21.0 months). Conclusion: Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy.

KW - AIDS

KW - HIV infection

KW - Kaposi's sarcoma

KW - Paclitaxel

KW - Protease inhibitors

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