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 (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,
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.