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 5-year survival rate for patients with pancreatic cancer is less than 5%.
The treatment was developed by the Brown University Oncology Group in a study of 34 patients with either pancreatic or gastric cancer. Although the study was designed to determine the optimal dose of paclitaxel(Drug information on paclitaxel) (Taxol) to administer to patients who also are receiving radiation treatment, the researchers were surprised to find that the regimen demonstrated substantial antitumor activity. Tumor reduction was noted in 70% of the patients with stomach cancers and 31% of those with pancreatic cancers.
Most pancreatic and stomach tumors are hard to detect at an early stage. By the time they are found, these tumors often have 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, MD, tumor regression occurred rapidly in certain patients, often within 3 weeks after treatments began. After 2 months of treatments, tumors in several patients had decreased to a size to where they could be removed surgically.
Paclitaxel Increases Tumor Radiosensitivity
"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 mutation of the p53 gene 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 appeared in the February issue of the Journal of Clinical Oncology. In the study, Safran and colleagues administered 3-hour IV doses of paclitaxel weekly for 6 weeks. After each infusion, patients received radiation. Several patients in the study experienced abdominal pain, nausea, anorexia, and other side effects of paclitaxel.
Further Studies of Combination Therapy Planned
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 M. D. 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.