LOS ANGELES--By using hyper-fractionation, radiation oncologists at Wayne State University were able to deliver an isocenter dose of 85 Gy to the prostate in men with locally advanced prostate cancer, producing a 95% negative biopsy rate.
"Instead of giving a standard fraction of 1.8 to 2.0 Gy once a day up to a standard total dose of about 70 Gy, we gave 1.15 Gy twice a day," said Jeffrey D. Forman, MD, in an interview about his poster presentation at the American Society for Therapeutic Radiology and Oncology (ASTRO) (see illustration).
Using conformal radiation and 3D treatment planning in prostate cancer patients, researchers have been able to reduce the amount of radiation to the surrounding normal tissue, but were still encountering significant complications at high doses. "Careful and precise aiming by itself was not sufficient to prevent complications to the rectum and bladder," Dr. Forman said, "so we turned to hyperfractionation, ie, the delivery of multiple, smaller than normal fractions of radiation each day."
No Severe Complications
Hyperfractionation is effective at treating cancer while sparing normal tissue, he said, because the effect of treatment on the cancer is dictated by the maximum total radiation dose, while the effect on normal cells depends more on the size of each individual dose.
In Dr. Forman's dose-escalation study using hyperfractionated conformal radiotherapy, there were no severe complications at the first dose level of 80 Gy, and about half the patients had negative findings on post-radiation biopsies, "an improvement over the 25% negative biopsy rate generally seen with standard doses," he said.
These patients were monitored for about a year before the researchers moved to the next dose level of 85 Gy. Again, there were no severe complications among the 24 patients receiving this dose level, and the negative biopsy rate rose to 95%.
This created a dilemma, Dr. Forman pointed out. Although the low toxicity justified continuing the study to the next dose level of 90 Gy, "because 95% of patients had no cancer in their biopsy specimen, we felt that ethically, it didn't make sense to continue to the next dose level, since it would be hard to improve on those results."
The researchers elected to close the study early and continue to monitor the patients who received the 85 Gy dose to make sure that local control rates are maintained. "If they are not maintained, then we will go to the next dose level; if they are, then we're done," Dr. Forman said, adding that the next goal would be to confirm the results in a larger clinical trial. Currently, he said, the patients have been followed for 2 to 4½ years.
In this protocol, the fractions were given at 6- to 8-hour intervals, so patients could come in at 7 or 8 AM for their first treatment and return about 4 PM for their second dose, he said, allowing patients who were working to work a full day between treatments. The treatment, which continued for 7½ weeks, was well tolerated, with patients able to maintain their normal daily activities.
Somewhat confounding the results was the fact that many patients also received preradiation hormonal therapy. "Between the time in early 1992 when we opened the study and treated patients at the first dose level and the time we started the second dose level, data on RTOG 8610 became available showing that in this population of patients, preradiation hormonal therapy is beneficial, so we elected to include that in the treatment regimen," he said. All but four patients at the second dose level received pretreatment hormones.
Dr. Forman acknowledged that the hormonal treatment contributed to the excellent results seen at the 85 Gy dose level. "Some people criticized the study, saying that by adding hormonal therapy, we were losing the ability to know how much was really gained from the increased dose, but from my perspective, the goal of the treatment is to get rid of the cancer without serious side effects, and if it takes two types of treatment to do that, I'm not really concerned with knowing the precise contribution of each treatment."
Dr. Forman's colleagues in the study were Arthur T. Porter, MD, Paul Kocheril, MD, David Grignon, MD, and Colin Orton, PhD.