Gemcitabine

Gemcitabine

Gemcitabine is a fluorine-substituted deoxycytidine analog that is phosphorylated initially by the enzyme deoxycytidine kinase to the monophosphate form and then by other nucleoside kinases to the diphosphate and triphosphate nucleotide forms. The antitumor effect is considered to result from several mechanisms: inhibition of ribonucleotide reductase by gemcitabine diphosphate, which reduces the level of deoxyribonucleoside triphosphates required for DNA synthesis; inhibition by gemcitabine triphosphate of DNA polymerase- and DNA polymerase- , thereby resulting in blockade of DNA synthesis and DNA repair; and incorporation of gemcitabine triphosphate into DNA, leading to inhibition of DNA synthesis and function. Following incorporation of gemcitabine nucleotide, only one additional nucleotide can be added to the growing DNA strand, resulting in chain termination.

This nucleoside analog was initially approved for use in advanced pancreatic cancer but is now widely used to treat a broad range of malignancies, including non-small cell lung cancer, bladder cancer, ovarian cancer, soft tissue sarcoma, and non-Hodgkin's lymphoma. Myelosuppression in the form of neutropenia is the principal dose-limiting toxicity. Nausea and vomiting occur in 70% of patients and a flu-like syndrome has also been observed. In rare cases, renal microangiopathy syndromes, including hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura have been reported.