PROVIDENCE, R.I.--Scientists have developed a drug and radiation regimen for reducing locally advanced and inoperable tumors in the pancreas and stomach.
The finding may be an important step toward a therapy for pancreatic and stomach malignancies. No effective treatments for these cancers currently exist. Indeed, the five-year survival rate for patients with pancreatic cancer is less than five percent.
The treatment was developed by the Brown University Oncology Group in a study of 34 patients with either pancreatic or gastric cancers. Although the study was designed to determine the optimal dose of the drug paclitaxel to administer to patients who also received radiation treatment, the researchers were surprised to find the regimen demonstrated substantial activity in the patients. The result was tumor reduction in 70 percent of the patients with stomach cancers and 31 percent of those with pancreatic cancers.
Most pancreatic and stomach tumors are hard to detect at an early stage. When they are found, the tumors have often spread locally into lymph nodes and surrounding blood vessels. These malignancies may be too extensive to remove by surgery, particularly in frail patients.
According to study leader Howard Safran, M.D., tumor regression occurred rapidly in certain patients, often within three weeks after treatments began. After two months of treatments, tumors in several patients had decreased to a size to where they could be removed surgically.
"Paclitaxel makes tumors much more sensitive to being killed by radiation," said Safran, an assistant professor of medicine in the Brown University School of Medicine, based at The Miriam Hospital and at Rhode Island Hospital.
"The new treatment can be used to shrink localized tumors," Safran said. "The idea is to get an effective treatment for these local cancers before surgery is attempted. Once the tumors shrink, they can be removed surgically."
In previous research, the Brown University Oncology Group had developed a one-two punch of paclitaxel and radiation that was effective against certain lung tumors, an approach that is now used worldwide. Cancers of the lung, stomach and pancreas often share a genetic mutation, labeled p53, that thwarts standard chemotherapy and radiation treatments. But a regimen of paclitaxel and radiation is effective in the presence of p53 mutations, Safran said.
The study of pancreatic and gastric tumors appears in this month's Journal of Clinical Oncology. In the study, Safran and colleagues administered three-hour intravenous doses of paclitaxel weekly for six weeks. After each paclitaxel infusion, patients received radiation. As with any drug, paclitaxel can cause unwanted side effects. Several patients in the study experienced abdominal pain, nausea, anorexia and other side effects.
Paclitaxel is derived from taxol, a chemical obtained from the bark of the yew tree. As a chemotherapy drug, paclitaxel is used for the treatment of ovarian, breast and lung cancer.
The study was funded partially by a grant from the National Institutes of Health. Safran and colleagues recently presented their findings to researchers at Memorial Sloan Kettering Hospital in New York and MD Anderson Cancer Center in Houston. Further clinical studies of the paclitaxel-radiation treatment are being planned nationwide, to be conducted by the Radiation Therapy Oncology Group, a collection of cancer researchers from across the country.