Kalpna Gupta, Ph.D., member of the Cancer Center's Breast Cancer Research Program, led the research.

MINNEAPOLIS / ST. PAUL (Dec. 5, 2007) — University of Minnesota cancer researchers have found that the combination of morphine and celecoxib, an anti-inflammatory analgesic drug, provides better pain relief for advanced cancer than either drug alone. In addition, their research, which was done in mice, shows that this drug combination prevents the growth and spread of cancer, and increases survival. Their findings are published in the current issue of the British Journal of Cancer.

"Severe pain is one of the major problems for people with advanced cancer and we know that if we can relieve the pain they experience, then we can also improve their quality and length of life," said Kalpna Gupta, Ph.D., assistant professor and breast cancer researcher with the University of Minnesota Medical School and Cancer Center. Gupta led the research team on this study.

"Our laboratory study in mice corroborates anecdotal observations by physicians and surgeons —that people who receive morphine plus celecoxib have better pain control," Gupta said.

She emphasized, however, that clinical trials are needed to determine whether the laboratory findings apply to cancers in humans. "These findings demonstrate the urgent need for clinical trials to address this question," she said. "It is premature for patients or their physicians to apply our laboratory findings to clinical treatment until after clinical trials have been done."

Morphine and related opioids are the main means used to treat serious pain in patients with advanced cancer, including breast cancer, that has spread to other parts of the body and bones. The downsides of morphine are that prolonged use in humans can result in tolerance and require higher dosages to achieve pain relief. In addition, earlier research done by Gupta and her colleagues showed that chronic morphine treatment can lead to increased tumor growth in mice. In the present study, they showed that chronic morphine treatment can also stimulate tumor spread (metastasis) along with increased tumor growth and a decreased length of survival in mice.

Celecoxib belongs to a family of drugs called nonsteroidal anti-inflammatory drugs, commonly known as COX-2 inhibitors because the drugs inhibit an enzyme called COX-2. Activation of COX-2 plays an important role in the promotion of blood vessel formation in tumors, increases tumor growth and the spread of the tumor to other organs in the body. Commercially available COX-2 inhibitors, like celecoxib, have been found to slow the progression and spread of cancer.

Gupta and her colleagues found that, over a two-week period, mice that had breast cancer and received chronic morphine treatment had increased tumor growth and spread, and reduced survival. By comparison, mice that received the combination of morphine and celecoxib did not show tumor growth or spread, and had increased survival.

"Our study provides proof of principle that the chronic use of morphine and related opioids stimulates COX-2 levels and leads to increased tumor blood vessels, tumor growth, spread, and mortality in mice," Gupta said. "We show that co-administering celecoxib reduces COX-2 levels in the tumors of mice treated with morphine and prevents morphine-induced tumor growth and metastasis, and increases survival. Furthermore, co-administration of celecoxib with morphine provides pain relief even after 14 days of treatment, which did not occur in mice treated with only morphine."

In addition to Gupta, the research was done by M. Farooqui, Y. Li, T. Rogers, T. Poonawala, and C.W. Song, all from the University of Minnesota, and R.J. Griffin of the University of Arkansas, Little Rock. This study was supported by grants from the National Institutes of Health and the Susan G. Komen Breast Cancer Foundation.

The University of Minnesota Cancer Center is part of the University's Academic Health Center and is designated a Comprehensive Cancer Center by the National Cancer Institute. For more information about the Cancer Center, call 612-624-2620 or visit www.cancer.umn.edu.

The British Journal of Cancer's mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence, and consistent high standards have made the British Journal of Cancer one of the world's premier general cancer journals.

Media Contacts:

Mary Lawson, Public Relations Director, University of Minnesota Cancer Center, 612-624-6165, 612-203-0819 (cell), mlawson@umn.edu.

Sara Buss, Academic Health Center, 612-626-7037, buss@umn.edu