Gemcitabine

Gemcitabine
Systematic (IUPAC) name
4-amino-1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-on
Clinical data
Trade names Gemzar
AHFS/Drugs.com monograph
Pregnancy cat. D(US)
Legal status  ?
Routes Oral, intravenous
Pharmacokinetic data
Protein binding <10%
Half-life Short infusions 32-94 minutes
for long infusions 245-638 minutes
Identifiers
CAS number 95058-81-4
ATC code L01BC05
PubChem CID 60750
DrugBank APRD00201
ChemSpider 54753 YesY
UNII B76N6SBZ8R YesY
KEGG D02368 YesY
ChEBI CHEBI:175901 YesY
ChEMBL CHEMBL888 YesY
Chemical data
Formula C9H11F2N3O4 
Mol. mass 263.198 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

Gemcitabine (pronunciation: jem-SITE-a-been) is a nucleoside analog used as chemotherapy. It is marketed as Gemzar by Eli Lilly and Company.

Contents

Pharmacology

Chemically gemcitabine is a nucleoside analog in which the hydrogen atoms on the 2' carbon of deoxycytidine are replaced by fluorine atoms.

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.[1]

Administration

Gemcitabine is administered by the intravenous route, since it is extensively metabolized by the gastrointestinal tract. Dose ranges from 1-1.2 g/m2 of body surface area according to type of cancer treated.[2]

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 esophageal cancer, and is used experimentally in lymphomas and various other tumor types. Gemcitabine represents an advance in pancreatic cancer care[citation needed]. It is also not as debilitating as some other forms of chemotherapy.

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.[3]

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.[4] 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. Gemcitabine was recently 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).

GemCarbo chemotherapy for lung cancer

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.[5] 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.

Side effects

The following side effects are common (occurring in more than 30%) for patients taking Gemcitabine:

  • Flu-like symptoms such as muscle pain, fever, headache, chills, and fatigue
  • Fever (within 6–12 hours of first dose)
  • Fatigue
  • Nausea (mild)
  • Vomiting
  • Poor appetite
  • Skin rash

Low blood counts. White and red blood cells and platelets may temporarily decrease, increasing risk of infection, anemia, and bleeding.

Nadir (low point), the time between chemotherapy cycles at which blood counts are at their lowest.

Onset: none noted Nadir: 10–14 days Recovery: day 21

Temporary increases in liver enzymes. Blood or protein in the urine.

These are less common side effects (occurring in 10-29%) for patients receiving Gemcitabine:

  • Diarrhea
  • Weakness
  • Hair loss
  • Mouth sores
  • Difficulty sleeping
  • Shortness of breath (see lung problems)

History

Gemcitabine was first synthesized in Larry Hertel's lab at Eli Lilly during the early 1980s.[6] It was intended as an antiviral drug, but preclinical testing showed that it killed leukemia cells in vitro.[6]

References

  1. ^ N. M. F. S. A. Cerqueira, P. A. Fernandes, M. J. Ramos (2007). "Understanding ribonucleotide reductase inactivation by gemcitabine". Chemistry, a European Journal 13 (30): 8507–15. doi:10.1002/chem.200700260. PMID 17636467. 
  2. ^ Chu E., DeVita V. T., "Physicians' Cancer Chemotherapy Drug Manual, 2007", Jones & Bartlett, 2007.
  3. ^ Oettle H, Post S, Neuhaus P, et al. (January 2007). "Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial". JAMA 297 (3): 267–77. doi:10.1001/jama.297.3.267. PMID 17227978. http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=17227978. 
  4. ^ Von Der Maase, H; Hansen, SW; Roberts, JT; Dogliotti, L; Oliver, T; Moore, MJ; Bodrogi, I; Albers, P et al. (2000). "Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study.". J Clin Oncol 18 (17): 3068. PMID 11001674. 
  5. ^ Macmillan GemCarbo chemotherapy
  6. ^ a b Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. pp. 259. ISBN 0-471-89979-8. 

External links


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Look at other dictionaries:

  • Gemcitabine — Général Nom IUPAC 2 deoxy 2 ,2 difluorocytidine No CAS …   Wikipédia en Français

  • gemcitabine — /jem sīˈtə bēn/ noun A synthetic cytotoxic drug used to treat various cancers …   Useful english dictionary

  • gemcitabine — A drug that is used to treat certain types of breast cancer, pancreatic cancer, ovarian cancer, and lung cancer and is being studied in the treatment of other types of cancer. Gemcitabine is a type of antimetabolite. Also called gemcitabine… …   English dictionary of cancer terms

  • Gemcitabine — Strukturformel Allgemeines Freiname Gemcitabin Andere Namen …   Deutsch Wikipedia

  • gemcitabine — noun A particular drug used in chemotherapy …   Wiktionary

  • gemcitabine — n. a cytotoxic drug that has an established role in the treatment of advanced non small cell lung cancer and pancreatic cancers. It is administered intravenously; side effects are less severe than those of other antimetabolites. Trade names:… …   The new mediacal dictionary

  • gemcitabine hydrochloride — A drug that is used to treat certain types of breast cancer, pancreatic cancer, ovarian cancer, and lung cancer and is being studied in the treatment of other types of cancer. Gemcitabine hydrochloride is a type of antimetabolite. Also called… …   English dictionary of cancer terms

  • gemcitabine hydrochloride — gem·cit·a·bine hy·dro·chlo·ride (jem sitґə bēn) [USP] a pyrimidine analogue, which acts as an antineoplastic by preventing DNA chain elongation; used in chemotherapy for pancreatic adenocarcinoma and non–small cell lung carcinoma;… …   Medical dictionary

  • 122111-03-9 — Gemcitabine Gemcitabine Général Nom IUPAC 2 deoxy 2 ,2 difluorocytidine No CAS …   Wikipédia en Français

  • 95058-81-4 — Gemcitabine Gemcitabine Général Nom IUPAC 2 deoxy 2 ,2 difluorocytidine No CAS …   Wikipédia en Français

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