Keck School of Medicine of the University of Southern California (USC) researchers at the USC Norris Comprehensive Cancer Center and Hospital presented important findings at the 2011 meeting of the American Society of Clinical Oncology, the largest conference on cancer research of the year.
A study led by research assistant Leonor Benhaim in the laboratory of Heinz-Josef Lenz, professor of medicine and preventive medicine at the Keck School, reveals evidence for the first time that a stem cell marker profile may be associated with tumor recurrence in stage II and stage III colon cancer.
The research may explain why chemotherapy used in conjunction with Avastin and Erbitux have not been effective in patients with this type of cancer. Clinical trials using new cytotoxic and targeted therapeutics — in which patients receive chemotherapy to prevent tumor recurrence — have so far been ineffective in patients with stage II and stage III colon cancer.
The team of researchers looked at blood and tissue specimens in 234 patients for genetic clues that could explain why chemotherapy has provided no benefit.
“The only way to make progress in treatment for stage II and III is to use and apply treatments that target colon cancer stem cells,” said Lenz. “Future clinical trials should use agents targeting stem cells in the adjuvant setting.”
A team from the USC Women’s Cancers program presented results from a study on BRCA1 and BRCA2 genes in minority and underserved patients. The team included Mary El-Masry, resident; Charite Ricker, genetic counselor; Darcy Spicer, chief, cancer medicine and blood disease and Debu Tripathy, chair, USC Women’s Cancer program.
The study focused on 52 women who were among 415 patients with breast or ovarian cancer or a family history who participated in genetic counseling. Three hundred and six of these patients underwent BRCA gene testing to determine a family background of the BRCA mutation, a likely indicator of breast or ovarian cancer.
Fifty-four percent of the women in the study had a BRCA1 mutation and 46 percent a BRCA2 mutation. The researchers were surprised at the high number of BRCA2 mutations in this population, which could be attributed to a number of factors including underreported or misreported family history.
“Very little information is available regarding these genes in minority and underserved populations,” said Tripathy. “Most of this patient population is likely to have poor access to health care insurance over their lifetimes, which presents a public health challenge.”
The study was supported by the USC Women’s Cancers program, the USC Norris Comprehensive Cancer Center and Hospital and the Lynne Cohen Foundation.
Also highlighted at the meeting was research by Agustin Garcia, associate professor of clinical medicine, indicating that patients with platinum-resistant/refractory ovarian cancer respond well to a new therapy, NKTR-102. The 71-patient trial was funded by Nektar Therapeutics, a pharmaceutical company.
The trial focused on women with advanced ovarian cancer who relapsed after six months of platinum-based therapy and had also received treatment with pegylated liposomal doxorubicin, the standard second-line treatment for patients who are platinum-sensitive. These patients tend to respond poorly to all chemotherapy.
The response rate to standard chemotherapy in this group of patients is expected to be approximately 10 percent and their survival at eight to 10 months. This study showed a high response rate of 20 percent among patients treated with NKTR-102 with survival at 13.9 months.
“Women whose cancer has progressed following treatment with platinum therapy represent a very high unmet medical need as there are currently no good treatment options available for these women,” said Garcia.
Research by Anthony El-Khoueiry, assistant professor of clinical medicine at the Keck School, has shown promising results for the combination of Abraxane (nab-paclitaxel) and Zactima (vandetanib) for patients with advanced pancreatic cancer.
As part of a phase I clinical trial aimed at identifying the safe dose of the drug combination, 29 patients with pancreatic cancer who had failed prior standard regimens were treated. Twenty-eight percent of patients experienced shrinkage of tumors and the median survival was 8.2 months.
While these results are limited by the small number of patients and need to be further validated, the outcomes noted in this study have generated high interest since they appear similar to or slightly better than outcome results reported historically in patients receiving first-line standard therapy with gemcitabine.
“Pancreatic cancer is one of the most challenging solid tumors to treat because of the limited number of available treatment options and because current treatments have a limited impact on patient survival,” said El-Khoueiry. “Once patients fail first-line treatment with gemcitabine, there are no standard options available.”
Nab-paclitaxel is a novel chemotherapy agent that more effectively penetrates tumors, while vandetanib is targeted therapy focused on genes in the cancer cells as well as genes in the tumor environment and blood vessels. Potential follow-up studies in pancreatic cancer patients are under discussion, El-Khoueiry said. The research was funded by AstraZeneca and Abraxis, both pharmaceutical companies.