Muscular toxicity from docetaxel in HIV-patient treated by ritonavir

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Muscular toxicity from docetaxel in HIV-patient treated by ritonavir

C. Pichard, J. Jezequel, A. Pont, M. Bascoulergue, A. Oufella, V. Duperrin, A. Fabreguettes

CH Robert Ballanger, Seine-Saint-Denis, Aulnay sous Bois, France

Background: In hospital patients are treated in different care units for their cancer
and for their chronicles diseases. Interactions between their treatments can lead to iatrogenic consequences.

Purpose: To report a case of a docetaxel-ritonavir interaction in a HIV-patient with breast cancer

Material and Methods: Informations including HIV treatment have been obtained from patient clinical history. Chemotherapy treatments were obtained from CHIMIO.

Results: A 36-year-old HIV-positive woman was diagnosed with breast cancer in February 2010. The HIV-infection was diagnosed in 1996. Since 2007 eighth line treatment contains atazanavir (boosted with ritonavir), tenofovir and emtricitabine.
Neoadjuvant chemotherapy contains four cycles of Epirubicine-Cyclophosphamide followed by four cycles of docetaxel. Patient received four cycles of EC without important side effects. Three days after her first docetaxel cycle she was admitted to emergencies for muscular pains interesting her legs. Docetaxel-ritonavir interaction was supposed because docetaxel was metabolized by CYP450-3A4 and ritonavir inhibited CYP450-3A4.HIV treatment couldn’t be changed because infection was well controlled with viral load below the limit of detection. So docetaxel dose was reduced from 100mg/m² to 65mg/m². However seven days after the second cycle patient was again admitted for muscular pains. Docetaxel was definitely stopped. another possiblechoice was to use vinorelbine but review of literature has showed
vinorelbine is also metabolized by CYP450-3A4. Thereby patient received two more cycles of Epirubicine-Cyclophosphamide beforemastectomy.

Conclusion: This case report highlights severity of potential interaction between docetaxel and ritonavir. Concomitant administration of these medications may increase docetaxel blood concentration probably due to the inhibition of CYP450 by ritonavir. So docetaxel must be avoided in HIV-patient treated by ritonavir. While these interactions are well known to clinicians treating HIV, they are probably less obvious to the clinician prescribing chemotherapy. The optimal care for cancers requires that practitioners attend multidisciplinary meeting around the file of the
patient

Reference: 16th Congress of EAHP. 30 March - 01 April 2011. Viena. Austria