Publications by authors named "Henrik Illum"

6 Publications

  • Page 1 of 1

Dry-heat Depyrogenation Ovens for Pharmaceutical Compounding Facilities.

Int J Pharm Compd 2015 May-Jun;19(3):182-92

Sterilization kills microorganisms in compounded preparations, on the implements used to prepare them, and on the vessels that contain them, but depyrogenation incinerates the remaining debris and renders the treated tool, container, or meditation pyrogen free. Depyrogenation is thus an essential step in the preparation of sterile compounds, and the pharmacist who dispenses those formulations is directly responsible for ensuring their safety, potency, and purity. Dry heat provided by a depyrogenation oven or tunnel is the pharmaceutical gold standard for ensuring the elimination of pyrogens. In this report, we describe several depyrogenation ovens that are compliant with Current Good Manufacturing Practice standards and are appropriate for use in aseptic-compounding facilities that meet the guidelines set forth in United States Pharmacopela Chapter <797>.
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February 2016

Phase I dose escalation trial of nitroglycerin in addition to 5-fluorouracil and radiation therapy for neoadjuvant treatment of operable rectal cancer.

Surgery 2015 Aug 9;158(2):460-5. Epub 2015 May 9.

VA North Texas Health Care System Department of Hematology Oncology, Radiation Oncology, and Surgery/University of Texas Southwestern, Department of Surgery and Radiation Oncology, Dallas, TX. Electronic address:

Background: Nitric oxide donors decreased cell survival in vitro and tumor load in vivo in models of rectal cancer subjected to ionizing radiation. Nitroglycerin (NTG) transdermal patches, added to chemotherapy, have been shown to improve outcomes in lung cancer patients.

Methods: This open-label, nonrandomized, multicohort, dose escalation, phase I trial had a primary endpoint to evaluate the safety, tolerability, feasibility, dose-limiting toxicity and maximum tolerated dose of topical NTG in addition to 5-fluorouracil and radiation therapy for neoadjuvant treatment of locoregionally advanced operable rectal cancer. The secondary endpoint was rate of pathologic complete response (pCR). Patients were assigned to 3 sequential cohorts of escalating dose levels of commercially available NTG patches (0.2, 0.4, and 0.6 mg/h), each cohort was intended to consist of 3 patients.

Results: Thirteen patients were enrolled in the trial as specified in the dose escalation protocol. They were all male with a median age of 59.4 ± 2.5 (SEM) years. The observed toxicities were mild to moderate and manageable. Four patients developed asymptomatic grade 3 lymphopenia during the chemoradiation that resolved promptly upon completion. One patient had a non-ST segment elevation MI and 1 patient developed diarrhea. None of these toxicities were attributed to NTG except for 1 patient who developed a grade 3 headache. This required an additional group of patients at the same dose and no other patient experienced headaches. pCR was 17%.

Conclusion: NTG patches are well-tolerated and it is feasible to proceed with a phase II trial at the maximum dose examined (0.6 mg/h).
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http://dx.doi.org/10.1016/j.surg.2015.04.007DOI Listing
August 2015

Upper extremity venous thrombosis in patients with cancer with peripherally inserted central venous catheters: a retrospective analysis of risk factors.

J Oncol Pract 2013 Jan;9(1):e8-12

University of Texas Southwestern Medical Center, Department of Palliative Care, Dallas, TX 75390-8889, USA.

Purpose: Peripherally inserted central catheters (PICCs) are often used in place of mediport catheters because of cost and lack of operating room time and to prevent delays in therapy. One common complication associated with their use is upper extremity venous thrombosis (UEVT). The purpose of this study was to ascertain risk factors associated with an increased risk of PICC-associated UEVT in patients with cancer.

Methods: Retrospective analysis identified 237 patients with cancer who received PICCs at the Dallas Veterans Affairs Medical Center from 2006 to 2009. We analyzed many risk factors, including PICC infection (PI), use of erythropoiesis-stimulating agents (ESAs), antiplatelet agents (APAs), treatment dose anticoagulation (TDA), and bevacizumab.

Results: Of 237 patients, 36 (15%) were found to have UEVT. Stepwise logistic regression analysis showed risk factors positively associated with UEVT were use of ESAs (odds ratio [OR], 10.66; 95% CI, 2.25 to 50.49), hospitalization (OR, 2.38; 95% CI, 1.05 to 5.39), PI (OR, 2.46; 95% CI, 1.03 to 5.86), and TDA (OR, 8.34; 95% CI, 2.98 to 23.33), whereas patients receiving APAs had a lower risk of UEVT (OR, 0.25; 95% CI, 0.07 to 0.92).

Conclusion: Specific factors significantly increase the risk of UEVT in patients with cancer with PICCs, whereas use of APAs seems to have a protective effect against UEVT. These results may aid in the development of a predictive model for identifying patients at high risk of UEVT who may benefit from APAs, as well as in determining preventive strategies for reducing the risk of PICC-associated UEVT.
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http://dx.doi.org/10.1200/JOP.2012.000595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545673PMC
January 2013

Current status of radiosensitizing agents for the management of rectal cancer.

Authors:
Henrik Illum

Crit Rev Oncog 2012 ;17(4):345-59

Department of Hematology Oncology, Assistant Professor of Medicine, University of Texas Southwestern, 4500 S. Lancaster Road, Dallas, TX 75216, USA.

The management of locally advanced rectal cancer requires a multidisciplinary effort. Surgical resection remains the therapeutic cornerstone, but neoadjuvant chemoradiation clearly improves both surgical and long-term outcomes. Pathological complete response is a desirable outcome and has been associated with good long-term outcomes. This article provides an overview of the evolution and current role of radiosensitizing chemotherapy when given as part of neoadjuvant chemoradiation for locally advanced rectal cancer. 5-fluorouracil, given either as an infusion or orally as capecitabine, appears to have the most favorable balance of efficacy and tolerability at the present time. Oral administration without need for central IV access makes capecitabine an attractive option. Oxaliplatin and irinotecan have demonstrated increased toxicity without substantial associated improvement in outcomes. Both bevacizumab and cetuximab appear feasible when given with radiosensitizing chemotherapy, but no strong signal of improved efficacy has been demonstrated so far. There is currently a great need for new radiosensitizing agents and predictive biomarkers to help optimize the use of existing therapeutics. Increased topoisomerase I expression and increased EGFR gene copy number as possible predictors of response to irinotecan- and cetuximab-based chemoradiation, respectively, deserve further studies.
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http://dx.doi.org/10.1615/critrevoncog.v17.i4.40DOI Listing
February 2013

Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies.

Drugs 2012 Dec;72(17):2207-22

VA North Texas Health Care System, Dallas, TX 75216, USA.

Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway. Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which is seen in approximately 50% of all melanomas. In a randomized phase III trial, it was superior to dacarbazine in first-line treatment of advanced melanoma, with an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 0.26; 95% CI 0.20, 0.33; p < 0.001) and a statistically superior 12-month overall survival (OS) rate of 55% versus 43% (HR 0.62 [95% CI 0.49, 0.77]). Vemurafenib is generally well tolerated, but its use can be associated with development of cutaneous neoplasms such as squamous cell carcinoma (SCC) and keratoacanthoma (KA). These lesions can be excised safely without the need for withholding the drug or reducing its dose. Mechanisms of resistance to vemurafenib do not involve development of secondary mutations in the BRAF kinase domain, but may be related to BRAF V600E over-amplification, bypassing mechanisms via upregulation and overexpression of other components in the MAPK signalling cascade or activation of alternative pathways with potential to enhance cell growth, proliferation and survival. Clinical trials to test the efficacy of vemurafenib in combination with immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment of advanced melanoma are currently underway. Also under investigation is the use of vemurafenib in other solid tumours with BRAF mutations, such as papillary thyroid cancer.
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http://dx.doi.org/10.2165/11640870-000000000-00000DOI Listing
December 2012

Irinotecan and radiosensitization in rectal cancer.

Authors:
Henrik Illum

Anticancer Drugs 2011 Apr;22(4):324-9

Department of Hematology and Oncology, University of Texas Southwestern at Dallas and Dallas VA Medical Center, Dallas, Texas 75201, USA. Henrikb.illum@ va.gov

Neoadjuvant radiation therapy with concurrent 5-fluorouracil-based chemotherapy is currently considered the standard of care for locally advanced rectal cancer. Pathologically complete response is a desirable outcome and has been associated with increased disease-free survival. There is a need to improve on this approach given that only approximately 10% achieve a pathologically complete response. Irinotecan has an established role in the treatment of metastatic rectal cancer. Both in-vitro and in-vivo data have shown promising radiosensitization properties. This study provides an overview of the published clinical trials evaluating the role of irinotecan as a radiosensitizer in the management of locally advanced rectal cancer. Although early-phase clinical trials initially showed promising results, this did not translate into improved outcome in a larger randomized phase II trial. Increased topoisomerase I expression has recently been identified as a possible predictive marker for improved response to irinotecan-based radiosensitization. This finding could help identify a subset of patients more likely to benefit from the addition of irinotecan in future trials.
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http://dx.doi.org/10.1097/CAD.0b013e3283425c14DOI Listing
April 2011