|ATC code||L01BC05 (WHO)|
|Biological half-life||Short infusions: 32–94 minutes
Long infusions: 245–638 minutes
|Chemical and physical data|
|Molar mass||263.198 g/mol|
|3D model (Jmol)||Interactive image|
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 esophageal cancer, and is used experimentally in lymphomas and various other tumor types.
Gemcitabine is administered by the intravenous route, since it is extensively metabolized by the gastrointestinal tract.
Gemcitabine became first line treatment for bladder cancer Stage 4 with metastases in combination with cisplatin after a study in 2000 with 405 patients showed similar efficacy but less toxicity compared to the former MVAC regimen. This new CG-regimen involves taking cisplatin on day 2 and taking gemcitabine on days 1, 8, and 15.
In July 2006 the FDA approved gemcitabine for use with carboplatin in the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based (e.g., carboplatin or cisplatin) therapy. Neutropenia was the most commonly reported adverse effect (90% of patients). Other serious adverse effects were mostly hematologic.
GemCarbo chemotherapy, consisting of a combination of gemcitabine and carboplatin, is used to treat several different types of cancer, but is most commonly used to treat lung cancer. GemCarbo chemotherapy is usually given as a day patient treatment, involving a blood test the day before, and the drugs are given by an infusion. The GemCarbo regimen is given as a 21-day cycle and on the first day of treatment the patient is given both the gemcitabine and carboplatin. On the same day of the following week (day eight) there is a drip of gemcitabine only. There then follows a rest period of two weeks which completes one cycle of chemotherapy. The next cycle of treatment is given after a rest period, which will be three weeks after the first injection. Usually 4–6 cycles of treatment are given over a period of 3–4 months and this makes up a course of treatment.
- Flu-like symptoms such as muscle pain, fever, headache, chills, and fatigue
- Fever (within 6–12 hours of first dose)
- Nausea (mild)
- Poor appetite
- Skin rash
- Allergic reaction
- Hair loss
- Mouth sores
- Difficulty sleeping
- Shortness of breath
As with fluorouracil and other analogues of pyrimidines, the triphosphate analogue of gemcitabine replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as only one additional nucleoside can be attached to the "faulty" nucleoside, resulting in apoptosis.
Another target of gemcitabine is the enzyme ribonucleotide reductase (RNR). The diphosphate analogue binds to RNR active site and inactivates the enzyme irreversibly. Once RNR is inhibited, the cell cannot produce the deoxyribonucleotides required for DNA replication and repair, and cell apoptosis is induced.
Gemcitabine was first synthesized in Larry Hertel's lab at Eli Lilly during the early 1980s. It was intended as an antiviral drug, but preclinical testing showed that it killed leukemia cells in vitro. It was first licensed in the UK in 1995.
A study reported in the Journal of the American Medical Association in 2007 suggested that gemcitabine showed benefit in patients with pancreatic cancer who were felt to have successful tumor resections.
Gemcitabine was also investigated for advanced cancer of the biliary tract and gallbladder and was found to have a modest effect on the tumor when combined with cisplatin (NEJM 2010).
As with many nucleoside analogues, gemcitabine may show antiviral activity as well as anti-cancer properties. Preliminary in vitro and mouse studies have shown it to be effective against enteroviruses such as coxsackievirus and poliovirus, as well as showing weaker activity against rhinoviruses, influenza and HIV, though it remains unclear whether gemcitabine is safe and effective enough in these applications to be developed for medical use as an antiviral agent.
- "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
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- Macmillan GemCarbo chemotherapy
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- Trial Sets New Standard for Pancreatic Cancer - Adjuvant combination almost doubled 5-year survival. June 2016
- ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma. June 2016
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- Zhang Z, Yang E, Hu C, Cheng H, Chen CY, Huang D, Wang R, Zhao Y, Rong L, Vignuzzi M, Shen H, Shen L, Chen ZW. Cell-based high-throughput screening assay identifies 2', 2'-difluoro-2'-deoxycytidine Gemcitabine as potential anti-poliovirus agent. ACS Infect Dis. 2016 Oct 12. PMID 27733043