gemcitabine

Gemcitabine is a nucleoside analogue used as a chemotherapy agent. It is a difluorinated analogue of deoxycytidine designed to disrupt DNA synthesis in cancer cells. After cellular uptake, gemcitabine is phosphorylated to active metabolites, including difluorodeoxycytidine triphosphate (dFdCTP) and difluorodeoxycytidine diphosphate (dFdCDP).

Mechanism of action relies on two main effects. The diphosphate metabolite inhibits ribonucleotide reductase, reducing the intracellular pool of deoxynucleotides and impeding DNA synthesis. The triphosphate metabolite is incorporated into DNA, causing chain termination and further impairment of DNA replication. These actions lead to apoptosis of rapidly dividing cancer cells.

Gemcitabine is approved for several solid tumors, including pancreatic cancer, non-small cell lung cancer, breast cancer, bladder cancer, biliary tract cancers, and ovarian cancer, often in combination regimens. Common combinations include gemcitabine with cisplatin for biliary tract cancers and with nab-paclitaxel for metastatic pancreatic cancer, among others. The choice of regimen depends on tumor type, patient factors, and prior therapy.

Administration is by intravenous infusion, with dosing and schedule tailored to the cancer type and regimen. Gemcitabine can cause myelosuppression, fatigue, fever, nausea, vomiting, mucositis, and rash. Other potential adverse effects include liver enzyme elevations and, rarely, pulmonary toxicity. Caution is advised in renal impairment, and treatment is generally avoided in pregnancy unless clearly indicated.