3 results
97856 Implementation of DPYD and UGT1A1 pharmacogenetic testing to guide chemotherapy dosing
- Lisa A. Varughese, Kelsey S. Lau-Min, Ursina Teitelbaum, AnnaClaire Osei-Akoto, Nandi Reddy, Nevena Damjanov, Ryan Massa, Sony Tuteja
-
- Journal:
- Journal of Clinical and Translational Science / Volume 5 / Issue s1 / March 2021
- Published online by Cambridge University Press:
- 30 March 2021, pp. 103-104
-
- Article
-
- You have access Access
- Open access
- Export citation
-
ABSTRACT IMPACT: The implementation of DPYD and UGT1A1 pharmacogenetic testing, a promising tool of precision medicine, translates evidence-based research into clinical oncology practice with personalized dosing to better predict interpatient variability in chemotherapy tolerability. OBJECTIVES/GOALS: Patients with DPYD and UGT1A1 genetic variants are at risk for severe toxicity from fluoropyrimidines and irinotecan, respectively. We propose that providing clinicians with the option to order a pharmacogenetic (PGx) test with relevant dose recommendations will increase test uptake to guide pharmacotherapy decisions and improve safety outcomes. METHODS/STUDY POPULATION: We plan to conduct a non-randomized, pragmatic, open-label study in 600 adult patients with gastrointestinal (GI) cancers initiating a fluoropyrimidine- and/or irinotecan-based regimen at three cancer centers within a health system. Implementation metrics of a new, in-house laboratory developed PGx test will be measured, including feasibility of returning results within one week, fidelity of providers following dose recommendations, and penetrance via test ordering rates. Clinical aims will include assessing severe toxicity during the first six months of chemotherapy. Outcomes will be compared to a historical control of GI cancer patients enrolled in a biobank and treated with standard dose chemotherapy. RESULTS/ANTICIPATED RESULTS: We anticipate that there will be an increase in PGx test uptake given its shorter turnaround time to facilitate clinical decision-making prior to the first dose of chemotherapy. Through integration of test results in the electronic health record (EHR) and clinical decision support tools for patients with actionable genotypes, we also expect that providers will have a high level of agreement to the recommended dose adjustments. We anticipate a decreased incidence of severe (Grade >3) toxicity among prospectively genotyped patients in the first six months of chemotherapy compared to DPYD and UGT1A1 variant carriers in the historical control group. Exploratory clinical utility data on costs of hospitalizations, chemotherapy treatment, PGx test, and medical services will also be reported. DISCUSSION/SIGNIFICANCE OF FINDINGS: This study aims to address barriers identified by key stakeholders to implementing PGx testing to better tailor chemotherapy dosing to the genetic profiles to patients. This may prevent adverse event-related hospitalizations, improve quality of life for patients, and reduce health system resource utilization costs.
2207: A Phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in patients with unresectable or borderline resectable pancreatic cancer
- Jacob Ezra Shabason, Jerry Chen, Smith Apisarnthanarax, Nevena Damjanov, Bruce Giantonio, Arturo Loaiza-Bonilla, Peter O’Dwyer, Mark O’Hara, Kim Reiss, Ursina Teitelbaum, Paul Wissel, Jeffery Drebin, Charles Vollmer, Michael Kochman, Rosemarie Mick, Norge Vergara, Nirag Jhala, Abigail Berman, Jay Dorsey, Sydney M. Evans, Gary Kao, John N. Lukens, John P. Plastaras, James M. Metz, Edgar Ben-Josef
-
- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, pp. 32-33
-
- Article
-
- You have access Access
- Open access
- Export citation
-
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
17 - Assessment, triage, and chemoembolization for colorectal liver metastases
- from Section IV - Organ-specific cancers – liver metastases
-
- By Michael C. Soulen, University of Pennsylvania, Govindarajan Narayanan, University of Miami, Ursina Teitelbaum, University of Pennsylvania
- Edited by Jean-Francois H. Geschwind, Michael C. Soulen
-
- Book:
- Interventional Oncology
- Published online:
- 05 September 2016
- Print publication:
- 22 September 2016, pp 148-157
-
- Chapter
- Export citation
-
Summary
The prognosis of patients with colorectal carcinoma rests largely on the presence or absence of distant metastases. In 2013, there were an estimated 142,820 new cases of colon cancer in the USA, with a prevalence of over 1.1 million and 50,830 annual deaths from the disease. Twenty percent of newly diagnosed patients already have metastases, and many more develop metastatic disease over time. The liver is the first and most common site, with 80% of stage IV patients having liver involvement and 40% of patients dying with the liver as their only site of metastases. Among patients with extrahepatic disease, more than half still die from liver failure. Resection of liver metastases improves long-term survival; however, for the 75% of patients who are not resectable, palliative treatments to delay cancer progression to fatal liver failure is the standard of care.
Assessment of the patient with liver metastases
Initial assessment of the patient with colorectal liver metastases incorporates the history and physical examination, review of laboratory studies including tumor markers, diagnostic imaging, and pathology. Performance status is an important prognostic factor, since patients with declining function (Eastern Cooperative Oncology Group (ECOG) > 2) tend not to benefit from liver-directed therapies despite being otherwise eligible to receive them.
High-quality anatomic and functional imaging is key for treatment planning and subsequent response assessment. Reports of diagnostic imaging studies alone do not provide the level of detail needed for triage and treatment planning. The interventional oncologist should carefully review anatomic imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) to assess segmental tumor burden. The first question to answer is if the patient is resectable, or could be converted to resectability through multidisciplinary interventions such as downstaging, ablation, or portal vein embolization. Close collaboration with a surgical oncologist can lead to potentially curative treatment plans even for multifocal disease. For unresectable disease, analysis of the size, location, and distribution of metastases in the liver will guide treatment planning among ablation and embolotherapies. High-quality imaging also depicts classical or variant arterial anatomy, status of the bile ducts and portal veins, and presence of ascites or extrahepatic disease. Positron emission tomography (PET)-CT shows fluorodeoxyglucose (FDG)-avidity in the majority of patients with metastatic colorectal cancer and can be helpful in following treatment response for therapies where conventional Response Evaluation Criteria In Solid Tumors (RECIST) imaging is less useful, such as ablation and embolization.