Gemcitabine

Overview
Gemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar® by Eli Lilly and Company.

Pharmacology
Chemically gemcitabine is a nucleoside analog in which the hydrogens on the 2' carbons of deoxycytidine are replaced by fluorides.

As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the "faulty" nucleoside, resulting in apoptosis (cellular "suicide").

Indications
Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types. Gemcitabine represents an advance in pancreatic cancer care. It is also not as debilitating as other forms of chemotherapy.

"Adjuvant Chemotherapy With Gemcitabine vs Observation in Patients Undergoing Curative-Intent Resection of Pancreatic Cancer: A Randomized Controlled Trial" reported in the Journal of the American Medical Association (JAMA. 2007;297:239.) suggest that gemcitabine shows benefit in patients with pancreatic cancer who were felt to have successful tumor resections.

Recently, research done at the Anderson Cancer Center in Texas on mice with pancreatic cancer has been done where cromolyn, an allergy and asthma drug with little side effects has been effective in binding with proteins that cancer cells produce. The long term prospects of this new development are very encouraging. Cromolyn is used for asthma, as an eye drop and can be taken orally to treat mastocytosis. The study was published on December 20, 2006 in a leading Cancer journal.

A protein produced by cancerous cells in the pancreas called S100P is found in excess among pancreatic cancer patients and is necessary for cancer cell growth and survival. In addition, S100P activates a cell surface protein receptor called RAGE.

Gemcitabine became first line treatment for bladder cancer Stage 4 with metastases in combination with Cisplatin after a study with 405 patients showed similar efficacy but less toxicity compared to the former MVAC regimen ( J Clin Oncol 2000;18:3068). This new CG-regimen is Cisplatin on day 2, Gemcitabine on days 1,8,15.