On the development of gemcitabine-based chemoradiotherapy regimens in pancreatic cancer.
The use of chemotherapy with concurrent radiation therapy remains a standard treatment option for patients with unresectable or resected adenocarcinoma of the pancreas. This treatment strategy is based in large part on data from serial Gastrointestinal Tumor Study Group trials that have included 5-fluorouracil. Unfortunately, the majority of patients continue to succumb to the disease process. Recently, there has been a resurgence in clinical trials utilizing gemcitabine as a single agent, in combination chemotherapy regimens, and with concurrent radiation therapy. Use with concurrent radiation therapy is based in part on laboratory studies investigating mechanisms of radiosensitization and strategies that might increase the therapeutic index. In the current review, the authors summarize the preclinical data that support the use of gemcitabine as a radiosensitizing agent and the clinical trials that have been conducted to date. Issues regarding the use of gemcitabine in concurrent radiotherapy regimens need to be viewed in the context of both local and distant disease control, given the radiosensitizing and systemic activity of this agent.
McGinn
Cornelius J
CJ
Department of Radiation Oncology, University of Michigan Health Systems, Ann Arbor, Michigan 48109-0010, USA. mcginn@umich.edu
Lawrence
Theodore S
TS
Zalupski
Mark M
MM
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine