National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
February 10, 2009 • Volume 6 / Number 3

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Cancer Research Highlights

Combining Targeted Drugs Is Worse in Colorectal Cancer

A randomized clinical trial testing chemotherapy combined with bevacizumab (Avastin) and cetuximab (Erbitux), and comparing this with chemotherapy and bevacizumab alone, found that the addition of cetuximab actually shortened patients’ recurrence-free and median survival. This runs counter to some studies using animal models of cancer, which suggest that combining a drug that targets vascular endothelial growth factor (VEGF) with a drug that targets epidermal growth factor receptor (EGFR) may be more effective than either drug alone. The trial results appeared February 5 in the New England Journal of Medicine.

Investigators from the Netherlands enrolled 755 patients with metastatic, inoperable colon or rectal cancer into the trial, continuing treatment until disease progression, death, or unacceptable side effects. Overall, “the addition of cetuximab significantly decreased the median progression-free survival” from 10.7 months to 9.4 months, they reported. Median overall survival was 20.3 months for patients receiving chemotherapy and bevacizumab and 19.4 months for patients receiving chemotherapy, bevacizumab, and cetuximab. Patients who received cetuximab reported less improvement in overall quality of life and health during treatment.

The researchers analyzed these results in the context of whether patients had tumors with the normal or mutated form of a gene called KRAS. Numerous studies have shown that only patients with normal KRAS genes benefit from drugs that target EGFR, including cetuximab. Patients with mutant KRAS who were given cetuximab had a significantly shorter progression-free survival than patients in the chemotherapy and bevacizumab arm; for patients with normal KRAS, cetuximab had no effect on progression-free survival.

The cause of these unexpected negative results are not clear, explained the authors, though a negative interaction between cetuximab and bevacizumab is one possibility.

Preserving Ovaries May Be Safe for Some Endometrial Cancer Patients

Because estrogen may fuel its spread, removing the uterus (hysterectomy) and the estrogen-producing ovaries (oophorectomy) is the standard of care for endometrial cancer. However, data from a retrospective study published online January 26 in the Journal of Clinical Oncology suggest that for premenopausal women with early stage, low-grade endometrial cancer, removing the ovaries may not actually improve survival.

Dr. Jason D. Wright and colleagues from the Columbia University College of Physicians and Surgeons used the SEER database to compare the survival of 2,867 endometrial cancer patients who underwent oophorectomy with that of 402 endometrial cancer patients whose ovaries were preserved. All of the women were diagnosed between 1988 and 2004 and had hysterectomies.

Women whose ovaries were preserved were younger, more likely to have low-grade and early stage tumors, and were also less likely to receive adjuvant radiation than women who underwent oophorectomy. There was no impact on disease-specific, 5-year, or overall survival, even after controlling for these differences. When the researchers excluded those women who received pelvic radiation, which could have affected ovarian function, there was still no survival advantage to oophorectomy.

Oophorectomy induces early menopause; thus, leaving the ovaries intact could spare these women hot flashes, vaginal dryness, and long-term health implications, including increased risk of heart disease, osteoporosis, and hip fractures. “Given the potential consequences of surgical menopause,” the authors concluded, “further research to examine the safety of ovarian conservation for young women with early stage endometrial cancer is clearly warranted.” They also emphasized that a woman’s options should be carefully discussed with her before deciding to undergo oophorectomy.

Costs Force Some Cancer Survivors to Pass on Health Care

Confronting the Cost of Cancer: Two New Reports

To assist people with cancer as they navigate the difficult and often emotional issues associated with the high costs of their health care, the American Society of Clinical Oncology (ASCO) last week released Managing the Cost of Cancer Care. This booklet has information about what patients can expect and offers suggestions for communicating effectively with their doctors about the costs. There is also a list of organizations that help patients facing financial challenges and a section on health insurance.

A second report out last week, Spending to Survive: Cancer Patients Confront Holes in the Health Insurance System, concludes that too often the health insurance system fails people when they need it most—when they are sick. The study, by the American Cancer Society and the Kaiser Family Foundation, profiles 20 patients and illustrates their difficulties in maintaining affordable health insurance and paying for their health care. An accompanying video can be viewed here.

Economic considerations are forcing an estimated 2 million cancer survivors to go without medical care, such as prescription medications, particularly survivors who are Hispanic or African American, NCI researchers report.

According to the results of a study presented last week at the American Association for Cancer Research Science of Cancer Health Disparities conference, nearly 1 in 10 cancer survivors don’t get prescriptions filled, nearly 8 percent pass on what they believe to be necessary general medical care, more than 11 percent skip needed dental care, and approximately 3 percent forgo mental health services because they are too costly.

That may mean going without, or significantly delaying, such care, explained the study’s lead author, Dr. Kathryn Weaver, a cancer prevention fellow in NCI’s Division of Cancer Control and Population Sciences. The results were not solely explained by access to health insurance. “There are significant out-of-pocket expenses, even for those with insurance,” Dr. Weaver said.

To conduct the study, the research team used 2003–2006 data from the CDC’s National Health Interview Survey (NHIS). They identified more than 6,600 cancer survivors, the large majority of whom were white, and compared them with more than 104,000 people who had no history of cancer. Compared with non-Hispanic whites, Hispanic and African American survivors were significantly more likely to forgo dental care and prescription medications, although, after adjusting for several variables, the disparity was reduced or eliminated. The NHIS is constructed to be representative of the U.S. population, allowing the researchers to arrive at the larger estimate of 2 million survivors who may forgo care due to cost concerns.

While data are not yet available for 2008, said Dr. Weaver, the recent economic downturn will likely make things worse.

“We know that one of the strongest predictors of forgoing care was not having health insurance coverage,” Dr. Weaver said. “If people lose their jobs and, as a result, their health insurance coverage, then the proportion forgoing care is likely to increase.”

Engineered Immune Cells Shrink or Eradicate Large Tumors in Mice

Researchers led by Dr. Carl June at the University of Pennsylvania in collaboration with scientists from NCI’s Center for Cancer Research have created genetically engineered human T cells (a type of immune-system cell) that can recognize and kill cancer cells expressing the protein mesothelin on their surface. Mesothelin is overexpressed in several cancer types that are highly resistant to traditional anticancer treatments, including mesothelioma (cancer of the lining of the chest or abdomen) and pancreatic, ovarian, and non-small cell lung cancer.

In a study published online February 9 in the Proceedings of the National Academy of Sciences, the researchers used a virus to transfer DNA encoding an engineered T-cell receptor into normal T cells. The engineered receptor consists of a protein that recognizes mesothelin attached to signaling proteins that cause the T cells to multiply and then search for and destroy tumor cells bearing a mesothelin target.

In cell-culture experiments, the engineered receptor was successfully expressed by the T cells. These immune cells were then able to identify and kill cancer cells that expressed mesothelin. The engineered T cells did not kill cells that did not express mesothelin.

The researchers implanted mice with mesothelioma cells that produced tumors. When the investigators injected the mice with the engineered T cells, the tumors shrank or were eradicated. One engineered T cell was capable of killing approximately 40 tumor cells, and the T cells persisted in the blood for several weeks after injection.

“Small doses of these cells may have potential in treating patients with large tumors. Clinical trials are being developed to investigate this approach in patients with mesothelioma and ovarian cancer,” said Dr. June in an accompanying press release.

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