Gemcitabine
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Non-proprietary name | Gemcitabine | |||||||||||||||||||||
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Molecular formula | C 9 H 11 F 2 N 3 O 4 | |||||||||||||||||||||
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Molar mass | 263,20 g · mol -1 | |||||||||||||||||||||
Physical state |
firmly |
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Melting point |
287–292 ° C (gemcitabine hydrochloride ) |
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As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . |
Gemcitabine (2 ′, 2′-difluorodeoxycytidine) is a nucleoside composed of cytosine and a difluorinated deoxyribose . It is a chemical analog of the nucleoside cytidine . It is used as a cytostatic in chemotherapy .
pharmacology
Mechanism of action
Gemcitabine is a cytostatic and is classified in the group of antimetabolites and belongs to the group of pyrimidine analogues. It is a prodrug that is only converted into its actual active form in the human cell.
The cytostatic effect of gemcitabine is based on the fact that instead of the human nucleoside cytidine, the active form of gemcitabine, gemcitabine diphosphate, is built into the DNA . This interrupts DNA synthesis and leads to cell death .
Absorption and distribution in the body
Since gemcitabine is only converted into the active form in the cell by an enzyme, this enzyme is of particular importance. The effectiveness of gemcitabine depends on the dose, but also on the duration of the infusion . Gemcitabine diphosphate is broken down into a cytostatically inactive substance
in the liver , blood and kidneys . It is excreted via the kidneys.
The biological half-life depends on the sex and age of the patient. It takes about 40 to 90 minutes.
Therapeutic use
application areas
- Therapy for adenocarcinoma of the pancreas (most common form of pancreatic cancer)
- Monotherapy or in combination with paclitaxel or with erlotinib
- Non-small cell lung cancer
- Combination with cisplatin
- Breast cancer (breast cancer)
- Combination with paclitaxel
- Combination with cisplatin
- Ovarian cancer (ovarian cancer)
- Combination with carboplatin
- Relapse therapy for lymphomas (non-Hodgkin and Hodgkin lymphomas)
- Combination with dexamethasone
- Monotherapy or in combination with cisplatin
unwanted effects
The most common side effects, which were observed in over 10 percent of those treated, are bone marrow damage , which manifests itself in a reduced number of granulocytes , platelets and leukocytes and anemia , shortness of breath , nausea and vomiting , increase in liver enzymes, allergic rashes and hair loss . Hematuria and proteinuria , as well as flu-like symptoms and edema .
The toxic side effects on the kidneys, liver and blood require careful monitoring of the patient in order to be able to make dose adjustments if necessary.
Side effects that are serious or can become severe, such as Stevens-Johnson syndrome , toxic epidermal necrolysis , posterior reversible encephalopathy syndrome (PRES), capillary leak syndrome , interstitial pneumonia , pulmonary edema , adult acute respiratory distress syndrome (ARDS), and anaphylactic reactions occur rarely (0.01-0.1 percent) to very rarely (less than 0.01 percent of those treated).
Interactions
- Radiation therapy for certain clinical pictures
Contraindications
Gemcitabine must not be used in the following cases:
- If you are hypersensitive to gemcitabine,
- Gemcitabine should not be given in the case of moderately to severely impaired liver function or severely impaired kidney function, as no relevant studies have been carried out.
dosage
Depending on the clinical picture, 1,000–2,000 mg / m 2 body surface area .
literature
- Pharmaceutical Therapy Criticism, Munich, 2005 Volume 37, pp. 121–128.
- Technical information: Gemzar.
- Textbook of Primary Care Medicine, 3rd ed, Mosby 2001.
Trade names
Cytogembin (A), Ebegemcit (A), Gemcapyr (A), Gemcitara (A), Gemzar (D, A, CH, EU), Tabinell (A), various generics (D, A, CH)
Web links
- Ricarda Wessinghage: Malignant liver diseases: prospect of a new therapy option with gemcitabine. Clinic of the Johann Wolfgang Goethe University, Frankfurt a. M., press release from September 15, 2006 at Informationsdienst Wissenschaft (idw-online.de), accessed on August 24, 2015.
Individual evidence
- ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, ISBN 978-0-911910-00-1 , p. 755.
- ↑ a b Data sheet Gemcitabine hydrochloride from Sigma-Aldrich , accessed on April 3, 2011 ( PDF ).
- ↑ David Goldstein, Robert Hassan El-Maraghi, Pascal Hammel, Volker Heinemann, Volker Kunzmann: nab-Paclitaxel Plus Gemcitabine for Metastatic Pancreatic Cancer: Long-Term Survival From a Phase III Trial . In: Journal of the National Cancer Institute . tape 107 , no. 2 , February 1, 2015, p. dju413 , doi : 10.1093 / jnci / dju413 , PMID 25638248 .