A Randomized Phase III Study of Gemcitabine in Combination with Radiation Therapy Versus Gemcitabine Alone in Patients with Localized, Unresectable Pancreatic Cancer: E4201
Prior studies of gemcitabine with radiation therapy in pancreatic cancer have concluded that the drug adds toxicity, with little, if any benefit. But, gemcitabine if known to make tissues more sensitive to radiation (called radiosensitization). This study was designed to further study the role of radiation with gemcitabine in unresectable pancreatic cancer.
The study was stopped early due to poor accrual. 71 patients (out of a planned 316) were randomly assigned to receive gemcitabine (G) or G + radiation therapy (GRT). As previously reported, patients with grade 4 (out of 0-4, 4 being most severe) toxicity was much greater in the GRT arm (41.2%), compared to the G arm (5.7%). Overall toxicity was similar, however. There was a small difference in overall survival, 9.2 months for G and 11 months for GRT.
Overall, it appears that radiation prolonged survival, but ultimately most patients still die, based on the overall survival over time that was presented by the authors. Weight loss, QOL, and toxicity were recorded but not reported at this time. Aggressive supportive care is essential, and we await reports of toxicity. With aggressive supportive care, it may be possible to escalate the dose of chemotherapy or radiation used in order to improve outcomes. Unfortunately, after nearly three decades of research, the role of radiation in pancreatic cancer is still not clear at present. These results do appear to affirm that radiation therapy and gemcitabine are more effective than gemcitabine alone, but due to the poor accrual, a larger study is still needed.