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: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Despite higher exposure to paclitaxel, patients on protease inhibitors did not experience enhanced toxicity or efficacy.
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. m-cianfrocca@northwestern.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Cianfrocca
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Jamie
authors.initials: J
authors.lastname: Von Roenn
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Rudek
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Dezube
authors.forename: Susan E
authors.initials: SE
authors.lastname: Krown
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018572:Disease-Free Survival; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010865:Pilot Projects; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017320:HIV Protease Inhibitors; D017239:Paclitaxel