Paclitaxel Plus Radiation Treatment May Shrink Pancreatic and Gastric Tumors

Scientists have developed a drug and radiation regimen for reducinglocally advanced and inoperable tumors in the pancreas and stomach.

The finding may be an important step toward a therapy for pancreaticand stomach malignancies. No effective treatments for these cancers currentlyexist. Indeed, the 5-year survival rate for patients with pancreatic canceris less than 5%.

The treatment was developed by the Brown University Oncology Group ina study of 34 patients with either pancreatic or gastric cancer. Althoughthe study was designed to determine the optimal dose of paclitaxel (Taxol)to administer to patients who also are receiving radiation treatment, theresearchers were surprised to find that the regimen demonstrated substantialantitumor activity. Tumor reduction was noted in 70% of the patients withstomach 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 intolymph nodes and surrounding blood vessels. These malignancies may be tooextensive to remove by surgery, particularly in frail patients.

According to study leader Howard Safran, MD, tumor regression occurredrapidly in certain patients, often within 3 weeks after treatments began.After 2 months of treatments, tumors in several patients had decreasedto a size to where they could be removed surgically.

Paclitaxel Increases Tumor Radiosensitivity

"Paclitaxel makes tumors much more sensitive to being killed byradiation," said Safran, an assistant professor of medicine in theBrown University School of Medicine, based at The Miriam Hospital and atRhode Island Hospital.

"The new treatment can be used to shrink localized tumors,"Safran said. "The idea is to get an effective treatment for theselocal cancers before surgery is attempted. Once the tumors shrink, theycan be removed surgically."

In previous research, the Brown University Oncology Group had developeda one-two punch of paclitaxel and radiation that was effective againstcertain lung tumors, an approach that is now used worldwide. Cancers ofthe lung, stomach, and pancreas often share a mutation of the p53 genethat thwarts standard chemotherapy and radiation treatments. But a regimenof paclitaxel and radiation is effective in the presence of p53 mutations,Safran said.

The study of pancreatic and gastric tumors appeared in the Februaryissue of the Journal of Clinical Oncology. In the study, Safran and colleaguesadministered 3-hour IV doses of paclitaxel weekly for 6 weeks. After eachinfusion, patients received radiation. Several patients in the study experiencedabdominal 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 Institutesof Health. Safran and colleagues recently presented their findings to researchersat Memorial Sloan-Kettering Hospital in New York and M. D. Anderson CancerCenter in Houston. Further clinical studies of the paclitaxel-radiationtreatment are being planned nationwide, to be conducted by the RadiationTherapy Oncology Group.