Researchers' new drug/radiation regimen may greatly improve prognosis for those with locally advanced and inoperable cancer
After being diagnosed with an uncommon form of pancreatic cancer in late 1995, life for Sarah (a pseudonym) became a two-month roller coaster ride. At first, she was told that surgery, the standard treatment, offered a high cure rate and that neither chemotherapy nor radiation would be effective.
But further tests revealed that surgery was impossible. The cancer was in a part of the pancreas, near major blood vessels and other sensitive sites, that prohibited its removal.
Sarah's surgeon encouraged her to take advantage of an indemnity add-on in her Harvard Community Health Plan (now called Harvard Pilgrim Health Care of New England) to get a second opinion. So, Sarah traveled to Boston to consult an out-of-network expert in pancreatic disease. But even he had seen just 26 cases of her hard-to-classify form of cancer. The Boston-based specialist confirmed that surgery was impossible and began preparations to attack the cancer with radiation aimed at her pancreas from outside her body and then "intraoperative" radiation administered after Sarah was opened and her pancreas exposed directly to the radiation source.
At about the same time, Sarah learned from her primary-care physician of a study in progress by Brown medical personnel of an experimental drug and radiation regimen for treating cancer in the pancreas or stomach. The physician consulted with the study leader to determine whether Sarah was a candidate.
In early 1996, Sarah joined the study. Every Monday for six weeks she received three-hour intravenous doses of the drug paclitaxel. For the rest of the week, she underwent radiation treatments, a total of 28 times over the six weeks. By spring 1996, the tumor in Sarah's pancreas had shrunk significantly.
For Sarah, the possibilities were now partial or total removal of the pancreas with or without intraoperative radiation, or intraoperative radiation alone. In reality, there was no way to predict what would be done until the pancreatic specialist in Boston opened up Sarah and looked inside.
"For whatever reason, my expectation going into the surgery was that removal of the tumor was still not going to be possible because of the likely involvement of critical blood vessels, and that I would have intraoperative radiation to buy me time, but nothing more than that," Sarah said.
In Boston that April, Sarah was opened. Doctors were able to remove two-thirds of her pancreas, including what was left of the tumor. A week and a half later, Sarah returned to work, and resumed the rest of her normal activities.
The medical community has never been able to effectively treat cancer in the pancreas or stomach. Indeed, the five-year survival rate for patients with pancreatic cancer is less than 5 percent. Sarah's story is a hopeful sign that the paclitaxel plus radiation regimen may greatly improve the prognosis for a patient with locally advanced, inoperable cancer in the pancreas and stomach.
According to study leader Howard Safran, M.D, most pancreatic and stomach tumors are hard to detect at an early stage. Once found, the tumors often have spread locally into lymph nodes and surrounding blood vessels. These malignancies may be too extensive to remove by surgery, he said.
Sarah, for example, was first hospitalized for the terrific pain in her pancreas in 1994. But it was only after a series of tests over the next 18 months and several attacks of acute pain that doctors found the cancer blocking one of her pancreatic ducts.
Meanwhile, the Brown University Oncology Group was testing paclitaxel on pancreatic and stomach cancers because their previous research to develop a paclitaxel and radiation regimen for certain lung tumors had led to a treatment now used worldwide. The research had shown that the regimen was effective in the presence of p53 genetic mutations, a condition frequently shared by cancers of the lung, stomach and pancreas.
"Paclitaxel makes tumors much more sensitive to being killed by radiation," said Safran, an assistant professor of medicine in the School of Medicine who is based at The Miriam and Rhode Island hospitals.
"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."
The study Sarah joined was designed to determine the optimal dose of the drug paclitaxel to administer to patients who would also receive radiation treatments. The research was conducted on 34 patients with either pancreatic or gastric cancers. During the study, the researchers were surprised to find that the regimen demonstrated substantial activity in the patients. Tumor regression occurred rapidly in certain patients, often within three weeks after treatments began. After two months of treatments, tumors in several patients, including Sarah, had decreased to a size to where they could be removed surgically. The final result was tumor reduction in 70 percent of the patients with stomach cancers and 31 percent of those with pancreatic cancers. The study appears in this month's Journal of Clinical Oncology.
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.
Just before her cancer was discovered, Sarah had read about the pluses and minuses of managed care. But she experienced none of the denial-of-health-care horrors described in some news stories. In her two-month surgery-or-no-surgery odyssey, she found medical personnel in and out of her health care network willing to help her and to cooperate with each other.
The result was Sarah's participation in a study with findings that may be an important step toward a therapy for pancreatic and stomach malignancies.
"You asked me if the treatment changed my outlook," said Sarah, smiling broadly, her voiced raised. "You bet it did!"