ATLANTA — Concurrent full-dose preoperative gemcitabine and radiation result in significant tumor response and acceptable toxicity in patients with resectable pancreatic cancer, according to data from a phase II multicenter trial.
In previous trials, investigators backed off from giving full-dose gemcitabine (Gemzar) with conventional whole-dose radiation because of high toxicity levels. This protocol, whose results are encouraging, was designed instead to deliver high levels of systemic chemotherapy with lower-dose radiation, Mark S. Talamonti, M.D., said at a symposium sponsored by the Society of Surgical Oncology.
The trial accrued 41 pancreatic cancer patients from five institutions. Twenty of the patients had resectable disease, while the rest showed no evidence of metastatic cancer but had unresectable disease.
Patients were treated preoperatively with three cycles of gemcitabine, and radiation was given during the second cycle. Cycles 1 and 3 consisted of 1,000 mg/m
Of the 20 patients taken to surgery, 17 (85%) underwent resections, including 16 pancreaticoduodenectomies and 1 distal pancreatectomy. Biopsy of metastases was performed only on the three patients who could not undergo resection. The complication rate was 24%, and there were no operative deaths. About one in four patients needed a vascular resection. This wasn't due to tumor adherence or invasion of the veins, but rather, was related to an “incredible fibrotic reaction” seen in the resected specimens, possibly as an effect of treatment, said Dr. Talamonti of Northwestern University, Chicago.
At 12 months' follow-up, 10 (59%) of the 17 patients who underwent resection were alive with no recurrence, 4 (24%) had distant metastases, and 3 (18%) had died.
Pathology revealed clear margins in 16 (94%) of the 17 patients who underwent surgery, and unresolved lymph nodes in 11 (65%) of the 17. One specimen contained no residual tumor, and three specimens revealed only microscopic foci of residual disease.
What some of the other trials underestimated is the capability of gemcitabine to serve as a radiation sensitizer, Dr. Talamonti noted. “What we tried to do is decrease the amount of radiation, assuming that gemcitabine was not only acting systemically but that it was also a potent radiation sensitizer,” he said.
Another advantage of the protocol is that there was no delay in surgery because it was well tolerated and caused no severe debilitation. All 20 patients underwent surgery within 6 weeks after their last gemcitabine infusion, which is comparable with other neoadjuvant trials, he said.
“I think that's a big advantage of this in addition to the response rates,” Dr. Talamonti said. He did not present data on the 21 patients with unresectable disease but said they exhibited higher levels of toxicity than patients with resectable disease because they started with a higher tumor load and had a generally lower performance status.
In general, these patients did show significant treatment responses, and some went on to exploratory surgery.
However, at this point it would be an overstatement to say that the protocol is something that can be used to downstage unresectable into resectable disease, Dr. Talamonti said.