Comparison of hyper-fractionated accelerated and standard fractionated radiotherapy with concomitant low-dose gemcitabine for unresectable pancreatic cancer.

Background: Concurrent chemoradiotherapy with gemcitabine improves median survival for patients with unresectable pancreatic cancer. Recently, hyper- fractionated accelerated radiotherapy (HART) has been used to treat these patients; however, the safety and efficacy are not well defined. Patients and Methods: The standard-fractionated radiotherapy (SFRT) group (n=17) received50.4Gyin28fractionsof1.8Gy/day.TheHART group (n=18) received 50 Gy in 40 fractions of 1.25 Gy twice/day. Concurrent gemcitabine was administered to both groups. Results: Median survival times were 11.3 months (SFRT) and 12.9 months (HART). One- and two- year survival rates were 37.5% and 18.8% (SFRT) and 47.1% and 17.6% (HART), respectively. The response rates did not differ significantly. The HART regimen requiredsignificantlyfewertreatmentdays(35.5)thandid theSFRTregimen(41.3).Thetoxicityprofilesweresimilar. Conclusion:TheHART/gemcitabineregimenhasequivalent efficacyandashortertreatmenttimeascomparedwiththe SFRT/gemcitabine regimen for patients with unresectable pancreaticcancer. Carcinoma of the pancreas is the fifth leading cause of cancer death and has a dismal prognosis, with the 5-year overall survival being only 1-4% (1). The nonspecific nature of early symptoms of pancreatic cancer may contribute to delayed diagnosis such that at the initial presentation, 80% or more of patients have locally advanced or metastatic disease that cannot be treated by surgical resection (2). Chemoradiotherapy has been generally accepted as the standard treatment for locally advanced pancreatic cancer (3- 5). Concomitant radiotherapy and 5-fluorouracil (5-FU) has been reported to modestly improve the median survival of patients with unresectable pancreatic cancer (3, 6). Gemcitabine (2,2'-difuluorooxycytidine), a nucleoside analog, has been found to radiosensitize a wide variety of human tumor cells in culture, particularly cells derived from carcinomas of the pancreas, breast, and head and neck (7, 8). The effect of radiation on local disease must be further enhanced in order to obtain local control and relief of the symptoms caused by disease progression. Hyper-fractionated radiotherapy (HART) was introduced as a way to increase the total tolerated dose and maximize local control without significantly increasing late complications, as compared with conventionally fractionated therapy (9). It involves the administration of multiple smaller irradiation dose fractions delivered at an increased frequency (commonly twice daily), allowing an increase in the total dose delivered over the same time as conventional radiotherapy, with equivalent long-term toxicities. A number of studies have reported feasibility and efficacy of combining HART and chemotherapy with gemcitabine for treating carcinomas of the head and neck and the lung (10, 11). However, there are few reports on the efficacy of concomitant HART and gemcitabine for treating pancreatic cancer. The primary end-point of this study was the feasibility and safety of concomitant HART and gemcitabine as compared to concomitant standard fractionated radiotherapy (SFRT) and gemcitabine. The secondary end-point was the overall survival measured from the date of therapy initiation.