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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

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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/m2) 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.

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Acknowledgments

The authors thank Dr. Fayez Hamzeh for performing the pharmacokinetic analysis when he was a faculty member at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Baltimore, MD), Dr. Michelle Till for her scientific contributions leading to the design of the study and Dr. David Scadden for contributing patients to the study. Supported in part by grants from the Department of Health and Human Services and the National Institutes of Health CA23318 to the Eastern Cooperative Oncology Group (ECOG) statistical center, CA66636 to the ECOG data management center, CA21115 to the ECOG coordinating center and chairman’s office, U01 CA121947 to the AIDS Malignancy Consortium.

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Authors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Mary Cianfrocca & Jamie Von Roenn

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Sandra Lee

  3. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA

    Michelle A. Rudek

  4. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Bruce J. Dezube

  5. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Susan E. Krown

  6. Montefiore-Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA

    Joseph A. Sparano

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  1. Mary Cianfrocca
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  2. Sandra Lee
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  3. Jamie Von Roenn
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  4. Michelle A. Rudek
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Correspondence to Mary Cianfrocca.

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Cianfrocca, M., Lee, S., Von Roenn, J. et al. 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. Cancer Chemother Pharmacol 68, 827–833 (2011). https://doi.org/10.1007/s00280-010-1509-4

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  • DOI: https://doi.org/10.1007/s00280-010-1509-4

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