Marked Tumor Response and Fatal Hemoptysis During Radiation for Lung Cancer in a Human Immunodeficiency Virus-Positive Patient Taking Nelfinavir

Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 5.28). 12/2009; 4(12):1587-9. DOI: 10.1097/JTO.0b013e3181bf111d
Source: PubMed


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    • "Preclinical in vivo studies suggest that in addition to direct effect on the tumor cells, PIs may inhibit PI3K-Akt activation in tumor vasculature, suppressing hypoxia pathways and leading to reduced radiation resistance [48,49]. Other clinical reports also suggest that PIs and radiotherapy interact on tumor vasculature similar to the effects of radiation and bevacizumab, an anti-angiogenic antibody [50]. "
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    ABSTRACT: 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. By 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. At 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. In 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.
    Radiation Oncology 03/2011; 6(1):25. DOI:10.1186/1748-717X-6-25 · 2.55 Impact Factor
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    ABSTRACT: Nelfinavir (Viracept) was originally designed as a specific HIV protease inhibitor and, since its introduction in 1997, has served as an effective, reliable, and well-tolerated HIV drug. Although nelfinavir is being increasingly displaced by second generation HIV protease inhibitors that allow better combination treatments, it has again become a focus of interest due to an interesting paradoxical effect: nelfinavir inhibits experimentally-induced tissue degeneration or cell damage by preventing loss of the mitochondrial membrane potential, and even protects mitochondria in cancer cells but, conversely, it selectively induces a mitochondria-independent cell death mechanism in cancer cells by the so-called endoplasmic reticulum/unfolded protein stress response, allowing nelfinavir to act on otherwise chemo-resistant cancer cells. Furthermore, anti-microbial effects of nelfinavir have been described, including an efficacy against malaria, tuberculosis, and SARS. Several cancer-related clinical studies on nelfinavir as a single agent or in combination therapies have been launched and are expected to add to the usefulness of this versatile drug for cancer treatment strategies or other purposes.
    Current Molecular Pharmacology 03/2010; 3(2):91-7. DOI:10.2174/1874467211003020091
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    ABSTRACT: Background: Human immunodeficiency virus (HIV)-infected patients are surviving longer since the advent of antiretroviral therapy. Therefore, more patients are developing non-AIDS-defining cancers which increasingly determine mortality. Case reports: Here we present 2 cases of locally advanced non-small cell lung cancer treated initially with concomitant chemoradiotherapy and antiretroviral therapy. Both patients were male, ages 69 and 66, with known HIV infection and immunologically stable on antiretroviral therapy. Presenting symptoms included superior sulcus tumor with left arm immobility and sensory disturbance in case 1 and right lower bronchus constriction in case 2. Symptoms were controlled by chemoradiotherapy. Conclusion: These cases illustrate that intensive anticancer therapy administered to the HIV-infected population can be tolerated even though these patients seem to be too fragile for both chemotherapy and radiotherapy, especially since the potential benefit remains uncertain. Recent improvements in chemoradiotherapy and supportive care have enhanced tolerance for such therapy.
    Onkologie 10/2013; 36(10):586-590. DOI:10.1159/000355162 · 0.86 Impact Factor

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