Jennifer Eads, MD, oncologist at UH Seidman Cancer Center, will present data from a Phase 1 clinical trial evaluating the toxicities and maximum tolerated dose of intravaneous methoxyamine when given with temozolomide, an oral chemotherapy drug, to patients with advanced solid tumors. Methoxyamine is a small molecule developed by researchers at UH Case Medical Center and Case Western Reserve University that has been found to enhance the effects of temozolomide based chemotherapy by targeting a pathway used to repair temozolomide-induced DNA damage.
Results of the study showed that 150 mg/m2 of methoxyamine may be safely administered with 200 mg/m2 of temozolomide with minimal toxicity. Antitumor activity in some tumor types was also observed.
"This early phase data shows the potential for a promising new combination treatment option for cancer patients with certain types of advanced solid tumors," says Dr. Eads, who is also Assistant Professor at Case Western Reserve University School of Medicine. "While this analysis focused on evaluating treatment dosing, we observed evidence of antitumor activity, particularly in neuroendocrine tumors, ovarian cancer and pancreatic adenocarcinoma and we look forward to conducting further clinical trials to further assess this drug combination."
The trial was funded by a grant from the National Cancer Institute (NCI) to the School of Medicine. This drug was recently selected by the NCI Cancer Therapy Evaluation Program for further drug development.
Also at ASCO 2015, Afshin Dowlati, MD, oncologist at UH Seidman Cancer Center, will present findings from two studies in small cell lung cancer (SCLC). In the first study analyzing gene mutations in patients with SCLC, an area in which limited genomic data currently exists, Dr. Dowlati has established a clinical-pathologic database on all SCLC patients treated at UH Seidman Cancer Center, one of the largest databases of its kind in the country, and recently added genomic analysis.
"Although small cell lung cancer impacts nearly 40,000 people each year in the United States, there is little genomic research being conducted for these patients," says Dr. Dowlati, who is also Professor at the School of Medicine. "Our research is the first to describe gene mutations in SCLC showing significant clinical correlation to overall survival, progression-free survival, and response to chemotherapy. We can expect that as our database grows, a full landscape of genes will emerge."
Dr. Dowlati and team examined 324 genes in specimens from 36 patients. Genes were organized into two groups: those with mutations validated to be oncogenic; and those harboring any detectable mutation. In the first group, progression-free survival was significantly worse for patients with no TP53 mutation compared to those without its presence. In the second group, two genes were identified as being predictive of overall survival, and three genes, were predictive of progression-free survival.
In the second presentation, Dr. Dowlati's laboratory has discovered that a subgroup of patients with SCLC have amplification of a gene called Rictor. This gene amplification in the laboratory leads to these cancers being responsive to drugs that will block Rictor. They hope to translate these findings into a clinical trial in the future.
"The breadth and depth of this innovative cancer research presented at ASCO is truly outstanding," says Stan Gerson, MD, Director of the Seidman Cancer Center at UH Case Medical Center and the Case Comprehensive Cancer Center at Case Western Reserve. "Our faculty members are making tremendous advances in hematology and oncology which is reflected in their being chosen for educational and poster presentations."
Presentations by UH Researchers at ASCO 2015
Poster Session, May 30, 8:00 - 11:30 a.m.
Phase I clinical trial of temozolomide and methoxyamine (TRC-102) in patients with advanced solid tumors (#2558)
Presenter: Jennifer Rachel Eads
Poster Session, May 30, 8:00 - 11:30 a.m
Association of tumor infiltrating lymphocytes (TILs) with pathologic response in baseline and post-brief exposure HER2+ breast cancer biopsies from BrUOG-211B (#619)
Presenter: Stefanie Avril
Poster Session, May 30, 1:15 - 4:45 p.m
Contemporary national trends of prostate cancer screening among privately insured patients in the United States (#5065)
Presenter: Simon P. Kim
Poster Session, May 31, 8:00 - 11:30 a.m
Outcomes and prognostic factors in marginal zone lymphoma: Case comprehensive cancer center cumulative experience of 358 cases (#8554)
Presenter: Adam Starr
Education Session, May 31, 11:30 a.m. - 12:45 p.m.
The Value Proposition in Oncology: Different Approaches to Understanding Value in Cancer Care
Presenter: Neal J. Meropol
Poster Session, June 1, 8:00 - 11:30 a.m.
Clinical correlation of genomic mutations in small cell lung cancer (#7575)
Presenter: Afshin Dowlati
Poster Session, June 1, 8:00 - 11:30 a.m.
Identification of RICTOR amplification as a recurrent and potentially actionable alteration in small cell lung cancer patients. (#7576)
Presenter: Snehal Dabir and Afshin Dowlati
Poster Session, June 1, 1:15 - 4:45 p.m.
Tumor infiltrating lymphocytes associated with brain metastasis in breast cancer (#2059)
Presenter: Nicole Olivia Williams
Education Session, June 1, 11:30 a.m. - 12:45 p.m.
New Therapies for Histologies Other than Adenocarcinoma? Track(s): Lung Cancer; Developmental Therapeutics and Translational Research
Presenter: Afshin Dowlati ?
Education Session, June 2, 9:45 - 11:00 a.m.
Making Sense of Emerging Therapies in Pancreatic Cancer: Are We Finally on the Right Track?
Presenter: Neal J. Meropol
INFORMATION:
About University Hospitals
University Hospitals, the second largest employer in Northeast Ohio with 25,000 employees, serves the needs of patients through an integrated network of 15 hospitals, 30 outpatient health centers and primary care physician offices in 15 counties. At the core of our $3.5 billion health system is University Hospitals Case Medical Center, ranked among America's 50 best hospitals by U.S. News & World Report in all 12 methodology-ranked specialties. The primary affiliate of Case Western Reserve University School of Medicine, UH Case Medical Center is home to some of the most prestigious clinical and research centers of excellence in the nation, including cancer, pediatrics, women's health, orthopaedics, radiology, neuroscience, cardiology and cardiovascular surgery, digestive health, transplantation and genetics. Its main campus includes UH Rainbow Babies & Children's Hospital, ranked among the top children's hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center at Case Western Reserve University. For more information, go to http://www.uhhospitals.org
