Acute toxicity of second generation HIV protease-inhibitors in combination with radiotherapy: a retrospective case series

Alfred P See,Phuoc T Tran,Michael Lim,Jing Zeng

doi:10.1186/1748-717x-6-25

Abstract

BackgroundThere is little data on the safety of combining radiation therapy and human immunodeficiency virus (HIV) protease inhibitors to treat cancers in HIV-positive patients. We describe acute toxicities observed in a series of HIV-positive patients receiving modern radiation treatments, and compare patients receiving HIV protease inhibitors (PI) with patients not receiving HIV PIs.MethodsBy reviewing the clinical records beginning January 1, 2009 from the radiation oncology department, we identified 29 HIV-positive patients who received radiation therapy to 34 body sites. Baseline information, treatment regimen, and toxicities were documented by review of medical records: patient age, histology and source of the primary tumor, HIV medication regimen, pre-radiation CD4 count, systemic chemotherapy, radiation therapy dose and fractionation, irradiated body region, toxicities, and duration of follow-up. Patients were grouped according to whether they received concurrent HIV PIs and compared using Pearson's chi-square test.ResultsAt baseline, the patients in the two groups were similar with the exception of HIV medication regimens, CD4 count and presence of AIDS-defining malignancy. Patients taking concurrent PIs were more likely to be taking other HIV medications (p = 0.001) and have CD4 count >500 (p = 0.006). Patients taking PIs were borderline less likely to have an AIDS-defining malignancy (p = 0.06). After radiation treatment, 100 acute toxicities were observed and were equally common in both groups (64 [median 3 per patient, IQR 1-7] with PIs; 36 [median 3 per patient, IQR 2-3] without PIs). The observed toxicities were also equally severe in the two groups (Grades I, II, III respectively: 30, 30, 4 with PIs; 23, 13, 0 without PIs: p = 0.38). There were two cases that were stopped early, one in each group; these were not attributable to toxicity.ConclusionsIn this study of recent radiotherapy in HIV-positive patients taking second generation PIs, no difference in toxicities was observed in patients taking PIs compared to patients not taking PIs during radiation therapy. This suggests that it is safe to use unmodified doses of PIs and radiation therapy in HIV cancer patients, and that it is feasible to use PIs as a radiosensitizer in cancer therapy, as has been suggested by pre-clinical results.

Highlights

There is little data on the safety of combining radiation therapy and human immunodeficiency virus (HIV) protease inhibitors to treat cancers in HIV-positive patients
Retrospective review Medical records for included patients were reviewed for HIV medications, cancer diagnosis and stage, radiation therapy, age at time of radiation therapy, cancer chemotherapy, acute (< 6 weeks after end of radiation therapy) toxicities categorized by Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade
antiretroviral therapy (ART) is typically initiated if the CD4 count is below 500, there are a number of other factors that contribute to the decision to initiate therapy, such as patient preference, adherence to prescriptions, and HIV strain

Summary

Introduction

There is little data on the safety of combining radiation therapy and human immunodeficiency virus (HIV) protease inhibitors to treat cancers in HIV-positive patients. We describe acute toxicities observed in a series of HIV-positive patients receiving modern radiation treatments, and compare patients receiving HIV protease inhibitors (PI) with patients not receiving HIV PIs. HIV and malignancies Historically, HIV infection is associated with a much higher risk of specific cancers [1,2,3,4]. Initial reports found increased radiotoxicity in HIV patients receiving treatment for Kaposi sarcoma, cervical carcinoma, while there was no difference in adverse effects of radiation therapy for other malignancies [10,11]. PIs are one class of anti-virals that is used as the ‘base’ in combination with two ‘backbone’ drugs for treatment of HIV, antiretroviral therapy (ART). There are currently ten PIs available; in chronological order of FDA approval, saquinavir, ritonavir, indinavir, nelfinavir, lopinavir, atazanavir, fosamprenavir (pro-drug of amprenavir, which is no longer available), tipranavir, and darunavir

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