Irinotecan and fixed-dose-rate gemcitabine in advanced pancreatic and biliary cancer: phase I study.
It is a continuing challenge for oncologists to effectively treat advanced/metastatic pancreatic and biliary cancer. Both irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have shown activity against these diseases with different mechanisms. Preclinical and clinical data also suggest additive or synergistic effects of the combination of these two agents with few or no overlapping toxicities. Phosphorylation of gemcitabine, a process of intracellular activation of the agent, is dose-rate dependent. It has been suggested that the fixed-dose-rate infusion of gemcitabine increases the concentration of intracellular triphosphate gemcitabine, which in turn may result in more objective responses and longer median survival compared to the standard infusion. This phase I study tests the toxicity of the combination of irinotecan with fixed-dose-rate infusion of gemcitabine, and determines the dose of the combination for phase II investigation.
Sun
Weijing
W
University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania, USA. weijing.sun@uphs.upenn.edu
Haller
Daniel
D
D000230:Adenocarcinoma / Q000188:drug therapy*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012107:Research Design; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine