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 Journal Article
| Authors: | Cianfrocca, M.; Lee, S.; Von Roenn, J.; Rudek, M. A.; Dezube, B. J.; Krown, S. E.; Sparano, J. A. |
| Article 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. © 2010 Springer-Verlag. |
| Keywords: | adult; clinical article; controlled study; disease-free survival; middle aged; clinical trial; fatigue; neutropenia; cytotoxic agent; area under the curve; diarrhea; drug efficacy; skin toxicity; paclitaxel; human immunodeficiency virus infection; neurotoxicity; progression free survival; infection; liver toxicity; lung toxicity; multiple cycle treatment; protease inhibitors; anemia; leukopenia; thrombocytopenia; antineoplastic agents, phytogenic; blood sampling; pilot study; pilot projects; cardiotoxicity; drug response; drug clearance; area under curve; drug toxicity; maximum plasma concentration; kaposi sarcoma; sarcoma, kaposi; drug blood level; motor dysfunction; urogenital tract disease; ileus; granulocyte colony stimulating factor; abdominal cramp; metabolic disorder; proteinase inhibitor; drug interactions; granulocytopenia; hiv infections; drug exposure; eye irritation; zidovudine; indinavir; aids; aids-related opportunistic infections; nelfinavir; hiv infection; kaposi's sarcoma; hiv protease inhibitors |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 68 |
| Issue: | 4 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2011-10-01 |
| Start Page: | 827 |
| End Page: | 833 |
| Language: | English |
| DOI: | 10.1007/s00280-010-1509-4 |
| PROVIDER: | scopus |
| PMCID: | PMC3112249 |
| PUBMED: | 21207228 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: CCPHD" - "Source: Scopus" |
