Effect of highly active antiretroviral therapy (HAART) on pharmacokinetics and pharmacodynamics of doxorubicin in patients with HIV-associated non-Hodgkin's lymphoma

G. Toffoli, G. Corona, G. Cattarossi, G. Boiocchi, G. Di Gennaro, U. Tirelli, E. Vaccher

Research output: Contribution to journalArticlepeer-review

Abstract

Background: We demonstrated that highly active antiretroviral therapy (HAART) increases the toxic effect of cyclophosphamide, vincristine, doxorubicin (DOX) and prednisone (CHOP) in HIV-patients with non-Hodgkin's lymphoma (NHL). To ascertain the cause of increased toxicity, we investigated the pharmacokinetics of DOX in HIV-patients with NHL treated with CHOP with and without HAART. Methods: Complete pharmacokinetics and pharmacodynamic analysis was determined in 19 patients during 38 cycles of chemotherapy: 19 cycles with CHOP and 19 CHOP+HAART in a crossover-designed study. HAART included protease inhibitors indinavir (IDV) in nine patients, saquinavir (SQV) hard gel in six patients and nelfinavir (NFV) in four patients. Results: No significant effects of HAART on pharmacokinetics parameters of DOX were observed. Similarly, no differential effect on DOX pharmacokinetics among IDV, SQV, and NFV was evidenced. Significant associations (P=0.012) were observed between DOX AUC0-∞ (area under the concentration curve) and G3-G4 WHO haematologic toxicity, in patients treated with CHOP alone, but not in those treated with CHOP + HAART (P = not significant). Conclusion: We demonstrated that HAART therapy has no significant effect on DOX pharmacokinetics. DOX AUC appears to be a predictor of toxicity only in patients treated with CHOP alone. Other factors beside DOX plasma levels are detrimental for toxicity after CHOP + HAART. Therefore, pharmacodynamic interactions between HAART and DOX should be considered.

Original languageEnglish
Pages (from-to)1805-1809
Number of pages5
JournalAnnals of Oncology
Volume15
Issue number12
DOIs
Publication statusPublished - Dec 2004

Keywords

  • CHOP
  • Doxorubicin
  • HAART
  • HIV
  • Interactions
  • Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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