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Investigational New Drugs

, Volume 35, Issue 2, pp 247–249 | Cite as

Safety of raltegravir-based antiretroviral therapy in HIV-infected patients receiving multi-kinase inhibitors

  • Pierre Loulergue
  • Mansouria Merad
  • Romain Coriat
  • Michel Ducreux
  • David Planchard
  • Valérie Boige
  • Axel Le Cesne
  • Thomas M. Gregory
  • Vianney Poinsignon
  • Angelo Paci
  • Olivier MirEmail author
SHORT REPORT

Summary

Background The risk of pharmacokinetic interaction is important in HIV-infected cancer patients receiving concomitantly highly active antiretroviral therapy (HAART) and anti-cancer systemic treatments. We aimed to evaluate the safety profile of raltegravir-based HAART in cancer patients receiving multi-kinase inhibitors (MKIs). Patients and Methods We conducted a retrospective medical record review of adult, HIV-infected cancer patients treated in our institutions from January 2010 to December 2015. Patients eligible for the present analysis were those receiving a raltegravir-based HAART at the time of the initiation of a MKI for the treatment of advanced solid tumors. Treatment-related toxicity, virological outcomes and pharmacokinetic profile of MKIs were examined. Results Twelve patients (7 males, median age 55 years) were identified. Seven had sarcoma/GIST, 3 had hepatocellular carcinoma, one had pancreatic neuroendocrine tumor, and one had NSCLC. Patients received the following MKIs: imatinib (n = 3), sorafenib (n = 3), pazopanib (n = 3), sunitinib (n = 2) and erlotinib (n = 1). The mean CD4+ count at baseline was 929 cells/mm3, and 860 cells/mm3 after completion of MKI treatment. In all patients, HIV viral loads remained below the limit of detection (40 copies/ mm3) during the whole MKI treatment. No virological failure occurred. No unexpected or serious adverse event related either to raltegravir-based HAART or to MKIs was observed. The trough plasma concentrations of MKIs were assessed in 8 patients, and were found normal in all but one case (not related to raltegravir-based HAART). Conclusions The present data represent the first documentation of the concomitant use of raltegravir-containing HAART and MKIs in HIV-infected adult patients with advanced non-AIDS defining malignancies, with a reassuring safety profile.

Keywords

Cancer HIV Raltegravir Tyrosine kinase inhibitors Drug-drug interactions CYP3A4 Pharmacokinetics 

Notes

Compliance with ethical standards

Conflicts of interest statement

Dr. Loulergue has acted as consultant for Pfizer.

Dr. Merad, Dr. Poinsignon and Prof. Gregory have no conflict of interest to declare.

Prof. Coriat has acted as consultant for Amgen, Bayer, Merck Serono, Novartis, Pfizer, Sanofi and Roche.

Prof. Ducreux has acted as consultant for Roche, Celgene, Merck Serono, Amgen, Sanofi, Novartis, Pfizer, Lilly, Servier.

Dr. Planchard has acted as consultant for Roche, GSK, Novartis, BMS and Astra-Zeneca.

Dr. Boige has acted as consultant for Merck Serono, Amgen, Sanofi-Aventis, Novartis and Bayer.

Dr. Le Cesne has acted as consultant for Amgen, Bayer, GSK, Lilly, Novartis, Pfizer, and PharmaMar.

Prof. Paci has acted as consultant for Amgen, BMS and Pierre Fabre.

Dr. Mir has acted as consultant for Astra-Zeneca, Amgen, Bayer, BMS, GSK, Lilly, Novartis, Pfizer and Roche.

Funding source

none.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

References

  1. 1.
    Loulergue P, Mir O, Allali J, Viard JP (2008) Possible pharmacokinetic interaction involving ritonavir and docetaxel in a patient with Kaposi's sarcoma. AIDS 22:1237–1239CrossRefPubMedGoogle Scholar
  2. 2.
    Mir O, Dessard-Diana B, Louet AL, Loulergue P, Viard JP, Langlois A et al (2010) Severe toxicity related to a pharmacokinetic interaction between docetaxel and ritonavir in HIV-infected patients. Br J Clin Pharmacol 69:99–101CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Spano JP, Poizot-Martin I, Costagliola D, Boué F, Rosmorduc O, Lavolé A et al (2016) Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH working group. Ann Oncol 27:397–408CrossRefPubMedGoogle Scholar
  4. 4.
    Torres HA, Rallapalli V, Saxena A, Granwehr BP, Viola GM, Ariza-Heredia E et al (2014) Efficacy and safety of antiretrovirals in HIV-infected patients with cancer. Clin Microbiol Infect 20:O672–O679CrossRefPubMedGoogle Scholar
  5. 5.
    Casado JL, Machuca I, Bañón S, Moreno A, Moltó J, Rodriguez MA (2015) Raltegravir plus two nucleoside analogues as combination antiretroviral therapy in HIV-infected patients who require cancer chemotherapy. Antivir Ther 20:773–777CrossRefPubMedGoogle Scholar
  6. 6.
    Bañón S, Machuca I, Araujo S, Moreno A, Perez-Elías MJ, Moreno S et al (2014) Efficacy, safety, and lack of interactions with the use of raltegravir in HIV-infected patients undergoing antineoplastic chemotherapy. J Int AIDS Soc 17:19590PubMedPubMedCentralGoogle Scholar
  7. 7.
    Hicks C, Gulick RM (2009) Raltegravir: the first HIV type 1 integrase inhibitor. Clin Infect Dis 48:931–939CrossRefPubMedGoogle Scholar
  8. 8.
    Widmer N, Bardin C, Chatelut E, Paci A, Beijnen J, Levêque D et al (2014) Review of therapeutic drug monitoring of anticancer drugs part two—targeted therapies. Eur J Cancer 50:2020–2036CrossRefPubMedGoogle Scholar
  9. 9.
    Tan AR, Gibbon DG, Stein MN, Lindquist D, Edenfield JW, Martin JC et al (2013) Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors. Cancer Chemother Pharmacol 71:1635–1643CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Pierre Loulergue
    • 1
  • Mansouria Merad
    • 2
  • Romain Coriat
    • 3
  • Michel Ducreux
    • 4
  • David Planchard
    • 4
  • Valérie Boige
    • 4
  • Axel Le Cesne
    • 4
  • Thomas M. Gregory
    • 5
  • Vianney Poinsignon
    • 6
  • Angelo Paci
    • 6
  • Olivier Mir
    • 4
    • 6
    Email author
  1. 1.Teaching Hospital Cochin, CIC Cochin-Pasteur, INSERM CIC1417Assistance Publique – Hôpitaux de Paris, University Paris DescartesParisFrance
  2. 2.Department of Emergency and Ambulatory Care, Gustave Roussy Cancer CampusVillejuifFrance
  3. 3.Department of Gastroenterology and Digestive Oncology, Teaching Hospital Cochin, Assistance Publique – Hôpitaux de ParisUniversity Paris DescartesParisFrance
  4. 4.Department of Cancer Medicine, Gustave Roussy Cancer CampusVillejuifFrance
  5. 5.Department of Orthopaedic Surgery, Teaching Hospital Avicenne, Assistance Publique – Hôpitaux de ParisUniversity Paris XIIIBobignyFrance
  6. 6.Department of Pharmacology, Gustave Roussy Cancer CampusVillejuifFrance

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