A phase III trial in patients with stage III non-small cell lung cancer (NSCLC) concludes that standard dose (SD) radiotherapy (60 Gy) is safer and more effective than high-dose (HD) radiotherapy (74 Gy), extending survival by nine months and causing fewer treatment related deaths. While 60 Gy is already standard, many doctors use higher doses expecting better outcomes. These findings should put an end to higher-dose treatment, given better outcomes in the standard dose arm.
Radiation therapy is used to control the growth of the primary tumor and cancer spread to the nearby (regional) lymph nodes. Although HD therapy in this patient population appeared promising in earlier phase I and phase II clinical trials, this study clearly shows that it is associated with dramatically shorter survival.
“We expected at the outset that high-dose radiation therapy would lead to better outcomes. We were surprised, though also pleased, to discover that less intense treatment led to better control of cancer progression and spread, and even improved overall survival,” said lead author Jeffrey D. Bradley, MD, a professor of radiation oncology at the Washington University School of Medicine in St. Louis, Mo. “The biological reasons for failure of the high dose with respect to overall survival and local-regional control are not readily apparent.”
In the study, 464 patients were randomly assigned to treatment with SD or HD radiation therapy along with standard chemotherapy (paclitaxel and carboplatin). In each treatment arm, the patients were also randomly assigned to receive cetuximab (Erbitux) or no additional therapy. Data on the effects of cetuximab on survival will be reported at a later date. The HD arm was closed after an interim analysis showed it was not superior to the SD arm.
The median survival for patients who received SD radiation therapy was much longer compared to that in patients who received HD radiation therapy (28.7 months vs. 19.5 months) and the estimated 18-month overall survival rates were also higher for the SD arm (66.9 percent vs. 53.9 percent). Cancer recurrence rates at 18 months were higher in the HD group of patients compared with the SD group (local recurrence rates were 34.3 percent vs. 25.1 percent, and distant recurrence rates were 44 percent vs. 35.3 percent). While the primary cause of death for most patients was lung cancer, there were a notably higher number of treatment-related deaths in the HD arm (10), compared to the SD arm (2).