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1,615 results on '"Ratain, Mark J."'

266. Validation of a Large Custom-Designed Pharmacogenomics Panel on an Array Genotyping Platform.

Author

Tang, Nga Yeung, Pei, Xun, George, David, House, Larry, Danahey, Keith, Lipschultz, Elizabeth, Ratain, Mark J, O'Donnell, Peter H, Yeo, Kiang-Teck J, and van Wijk, Xander M R

Subjects
PHARMACOGENOMICS, NUCLEOTIDE sequencing, SCATTER diagrams, DNA, CELL lines
Abstract

Background: Pharmacogenomics has the potential to improve patient outcomes through predicting drug response. We designed and evaluated the analytical performance of a custom OpenArray® pharmacogenomics panel targeting 478 single-nucleotide variants (SNVs). Methods: Forty Coriell Institute cell line (CCL) DNA samples and DNA isolated from 28 whole-blood samples were used for accuracy evaluation. Genotyping calls were compared to at least 1 reference method: next-generation sequencing, Sequenom MassARRAY®, or Sanger sequencing. For precision evaluation, 23 CCL samples were analyzed 3 times and reproducibility of the assays was assessed. For sensitivity evaluation, 6 CCL samples and 5 whole-blood DNA samples were analyzed at DNA concentrations of 10 ng/µL and 50 ng/µL, and their reproducibility and genotyping call rates were compared. Results: For 443 variants, all samples assayed had concordant calls with at least 1 reference genotype and also demonstrated reproducibility. However, 6 of these 443 variants showed an unsatisfactory performance, such as low PCR amplification or insufficient separation of genotypes in scatter plots. Call rates were comparable between 50 ng/µL DNA (99.6%) and 10 ng/µL (99.2%). Use of 10 ng/µL DNA resulted in an incorrect call for a single sample for a single variant. Thus, as recommended by the manufacturer, 50 ng/µL is the preferred concentration for patient genotyping. Conclusions: We evaluated a custom-designed pharmacogenomics panel and found that it reliably interrogated 437 variants. Clinically actionable results from selected variants on this panel are currently used in clinical studies employing pharmacogenomics for clinical decision-making. [ABSTRACT FROM AUTHOR]

Published
2021
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273. Quality of life impact three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma

Author

Ahles, Tim A., Herndon, James E., II, Small, Eric J., Vogelzang, Nicholas J., Kornblith, Alice B., Ratain, Mark J., Stadler, Walter, Palchak, David, Marshall, M. Ernest, Wilding, George, and Holland, Jimmie C.

Subjects
Suramin sodium -- Drug therapy, Suramin sodium -- Dosage and administration, Suramin sodium -- Patient outcomes, Prostate cancer -- Patient outcomes, Prostate cancer -- Case studies, Prostate cancer -- Complications and side effects, Quality of life, Health
Published
2004

277. A Phase II trial of Suramin monthly x 3 for Hormone-Refractory Prostate Carcinoma

Author

Vogelzang, Nicholas J., Karrison, Theodore, Stadler, Walter M., Garcia, Juan, Cohn, Helene, Kugler, John, Troeger, Thomas, Giannone, Leonard, Arrieta, Rose, Ratain, Mark J., and Vokes, Everett E.

Subjects
Dexamethasone -- Research, Chemotherapy -- Research, Prostate cancer -- Research, Hormone receptors -- Research, Health
Published
2004

282. Weekly, high-dose paclitaxel in advanced lung carcinoma

Author

Akerley, Wallace, Herndon, James E., Egorin, Merrill J., Lyss, Alan P., Kindler, Hedy K., Savarese, Dianne M., Sherman, Carol A., Rosen, D. Marc, Hollis, Donna, Ratain, Mark J., and Green, Mark R.

Subjects
Oncology, Experimental -- Analysis, Cancer patients -- Health aspects, Cancer patients -- Care and treatment, Cancer patients -- Drug therapy, Lung cancer -- Health aspects, Lung cancer -- Care and treatment, Lung cancer -- Drug therapy, Paclitaxel -- Physiological aspects, Paclitaxel -- Dosage and administration, Pharmacokinetics -- Research, Leukemia -- Health aspects, Leukemia -- Care and treatment, Health
Published
2003

289. Unsupported off-label chemotherapy in metastatic colon cancer

Author

de Souza Jonas A, Polite Blase, Perkins Monica, Meropol Neal J, Ratain Mark J, Newcomer Lee N, and Alexander G Caleb

Subjects
Colorectal cancer, Off-label, Evidence-based medicine, Physician practice patterns, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Newer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use. Methods We conducted a retrospective cohort study using commercial insurance claims from UnitedHealthcare, and identified incident cases of metastatic colon cancer (mCC) from July 2007 through April 2010. We evaluated the use of three regimens with recommendations against their use in the National Comprehensive Cancer Center Network Guidelines, a commonly used standard of care: 1) bevacizumab beyond progression; 2) single agent capecitabine as a salvage therapy after failure on a fluoropyridimidine-containing regimen; 3) panitumumab or cetuximab after progression on a prior epidermal growth factor receptor antibody. We performed sensitivity analyses of key assumptions regarding cohort selection. Costs from a payer perspective were estimated using the average sales price for the entire duration and based on the number of claims. Results A total of 7642 patients with incident colon cancer were identified, of which 1041 (14%) had mCC. Of those, 139 (13%) potentially received at least one of the three unsupported off-label (UOL) therapies; capecitabine was administered to 121 patients and 49 (40%) likely received it outside of clinical guidelines, at an estimated cost of $718,000 for 218 claims. Thirty-eight patients received panitumumab and six patients (16%) received it after being on cetuximab at least two months, at an estimated cost of $69,500 for 19 claims. Bevacizumab was administered to 884 patients. Of those, 90 (10%) patients received it outside of clinical guidelines, at an estimated costs of $1.34 million for 636 claims. Conclusions In a large privately insured mCC cohort, a substantial number of patients potentially received UOL treatment. The economic costs and treatment toxicities of these therapies warrant increased efforts to stem their use in settings lacking sufficient scientific evidence.

Published
2012
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295. Identification of a Genomic Region between SLC29A1 and HSP90AB1 Associated with Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance)

Author

Li, Megan, Mulkey, Flora, Jiang, Chen, O'Neil, Bert H, Schneider, Bryan P, Shen, Fei, Friedman, Paula N, Momozawa, Yukihide, Kubo, Michiaki, Niedzwiecki, Donna, Hochster, Howard S, Lenz, Heinz-Josef, Atkins, James N, Rugo, Hope S, Halabi, Susan, Kelly, William Kevin, McLeod, Howard L, Innocenti, Federico, Ratain, Mark J, Venook, Alan P, Owzar, Kouros, and Kroetz, Deanna L

Subjects
Vascular Endothelial Growth Factor A, Adult, Male, Oncology and Carcinogenesis, Angiogenesis Inhibitors, and over, Cardiovascular, Equilibrative Nucleoside Transporter 1, Clinical Research, Neoplasms, 80 and over, Human Umbilical Vein Endothelial Cells, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, HSP90 Heat-Shock Proteins, Oncology & Carcinogenesis, Aetiology, Neovascularization, Aged, Cancer, Pathologic, Clinical Trials as Topic, Human Genome, Middle Aged, Bevacizumab, Hypertension, Female, Genome-Wide Association Study, Biotechnology
Abstract

Purpose: Bevacizumab is a VEGF-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of multiple cancers. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy or lead to cardiovascular complications. The factors that contribute to interindividual variability in blood pressure rise during bevacizumab treatment are not well understood.Experimental Design: To identify genomic regions associated with bevacizumab-induced hypertension risk, sequencing of candidate genes and flanking regulatory regions was performed on 61 patients treated with bevacizumab (19 cases developed early-onset grade 3 hypertension and 42 controls had no reported hypertension in the first six cycles of treatment). SNP-based tests for common variant associations and gene-based tests for rare variant associations were performed in 174 candidate genes.Results: Four common variants in independent linkage disequilibrium blocks between SLC29A1 and HSP90AB1 were among the top associations. Validation in larger bevacizumab-treated cohorts supported association between rs9381299 with early grade 3+ hypertension (P = 0.01; OR, 2.4) and systolic blood pressure >180 mm Hg (P = 0.02; OR, 2.1). rs834576 was associated with early grade 3+ hypertension in CALGB 40502 (P = 0.03; OR, 2.9). These SNP regions are enriched for regulatory elements that may potentially increase gene expression. In vitro overexpression of SLC29A1 in human endothelial cells disrupted adenosine signaling and reduced nitric oxide levels that were further lowered upon bevacizumab exposure.Conclusions: The genomic region between SLC29A1 and HSP90AB1 and its role in regulating adenosine signaling are key targets for further investigation into the pathogenesis of bevacizumab-induced hypertension. Clin Cancer Res; 24(19); 4734-44. ©2018 AACR.

Published
2018

296. Drug Interactions With a Short Course of Nirmatrelvir and Ritonavir: Prescribers and Patients Beware.

Author

Ratain, Mark J. and Greenblatt, David J.

Subjects
*DRUG efficacy, *COVID-19, *COMBINATION drug therapy, *CYTOCHROME P-450, *DRUG-herb interactions, *ANTIVIRAL agents, *TREATMENT duration, *RITONAVIR, *DRUG interactions, *GLYCOPROTEINS, *CHEMICAL inhibitors, *THERAPEUTICS
Abstract

The article presents the discussion on unintended consequences of widespread distribution of a ritonavir-containing product. Topics include coformulation of N + R enabling the maintenance of effective antiviral concentrations of nirmatrelvir over a full 24-hour period with twice-daily dosing; and patients on chronic medications for conditions predisposing to severe COVID-19 infection.

Published
2022
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298. Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy

Author

Trendowski, Matthew R., primary, El-Charif, Omar, additional, Ratain, Mark J., additional, Monahan, Patrick, additional, Mu, Zepeng, additional, Wheeler, Heather E., additional, Dinh, Paul C., additional, Feldman, Darren R., additional, Ardeshir-Rouhani-Fard, Shirin, additional, Hamilton, Robert J., additional, Vaughn, David J., additional, Fung, Chunkit, additional, Kollmannsberger, Christian, additional, Mushiroda, Taisei, additional, Kubo, Michiaki, additional, Hannigan, Robyn, additional, Strathmann, Frederick, additional, Einhorn, Lawrence H., additional, Fossa, Sophie D., additional, Travis, Lois B., additional, and Dolan, M. Eileen, additional

Published
2019
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299. Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours

Author

Jones, Robin L., primary, Ratain, Mark J., additional, O'Dwyer, Peter J., additional, Siu, Lillian L., additional, Jassem, Jacek, additional, Medioni, Jacques, additional, DeJonge, Maja, additional, Rudin, Charles, additional, Sawyer, Michael, additional, Khayat, David, additional, Awada, Ahmad, additional, de Vos-Geelen, Judith M.P.G.M., additional, Evans, T.R. Jeffry, additional, Obel, Jennifer, additional, Brockstein, Bruce, additional, DeGreve, Jacques, additional, Baurain, Jean-Francois, additional, Maki, Robert, additional, D'Adamo, David, additional, Dickson, Mark, additional, Undevia, Samir, additional, Geary, David, additional, Janisch, Linda, additional, Bedard, Philippe L., additional, Abdul Razak, Albiruni R., additional, Kristeleit, Rebecca, additional, Vitfell-Rasmussen, Joanna, additional, Walters, Ian, additional, Kaye, Stan B., additional, and Schwartz, Gary, additional

Published
2019
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