Gemcitabine

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Gemcitabine
Systematic (IUPAC) name
4-amino-1-[3,3-difluoro-4-hydroxy-5- (hydroxymethyl) tetrahydrofuran-2-yl]- 1H-pyrimidin- 2-one
Identifiers
CAS number	95058-81-4
ATC code	L01BC05
PubChem	60750
DrugBank	APRD00201
Chemical data
Formula	C₉H₁₁F₂N₃O₄
Mol. mass	263.198 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	<10%
Metabolism	?
Half life	Short infusions 32-94 minutes for long infusions 245-638 minutes
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	Oral, intravenous

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

[edit] Pharmacology

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

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").

[edit] 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.

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.

[edit] External links

Gemzar.com

v • d • e Chemotherapeutic agents/Antineoplastic agents (L01)

Alkylating and alkylating-like agents	Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Bendamustine, Uramustine) Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin) Platinum (alkylating-like): (Carboplatin, Cisplatin, Oxaliplatin, Triplatin tetranitrate, Satraplatin) Alkyl sulfonates:(Busulfan, Treosulfan) Hydrazines:(Procarbazine, Dacarbazine, Temozolomide) Aziridines:(ThioTEPA)

Antimetabolites	Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed) Purine: (Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine) Pyrimidine: (Cytarabine, Decitabine, Fluorouracil/Capecitabine, Floxuridine, Gemcitabine)

Spindle poison/mitotic inhibitor	Taxane: (Docetaxel, Larotaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine).

Cytotoxic/antitumor antibiotics	Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Pixantrone, Valrubicin) streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) - Hydroxyurea

Topoisomerase inhibitors	Camptotheca: (Camptothecin, Topotecan, Irinotecan, Rubitecan), Podophyllum:(Etoposide, Teniposide)

CI monoclonal antibodies	Receptor tyrosine kinase (Cetuximab, Panitumumab, Trastuzumab) - CD20 (Rituximab, Tositumomab) - other (Alemtuzumab, Bevacizumab, Gemtuzumab)

Photosensitizers	Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin

Tyrosine kinase inhibitors	Axitinib, Bosutinib, Cediranib, Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Lestaurtinib, Nilotinib, Semaxanib, Sorafenib, Sunitinib, Vandetanib

Cyclin-dependent kinase inhibitor	Seliciclib

Other	retinoids (Alitretinoin, Tretinoin), Fusion protein (Aflibercept) - Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase (Pegaspargase), Bexarotene, Bortezomib, Celecoxib, Denileukin diftitox, Elesclomol, Estramustine, Irofulven, Ixabepilone, Masoprocol, Mitotane, Oblimersen, Testolactone, Tipifarnib, Trabectedin