Gemcitabine (Gemzar)

General information

Class/mechanism: Pyrimidine analog; metabolized within cells to the active nucleoside forms: diphosphate (dFdCDP) and triphosphate (dFdCTP). Gemcitabine diphosphate inhibits ribonucleotide reductase, which catalyzes reactions that produce deoxynucleoside triphosphates for DNA synthesis. This inhibition of deoxynucleoside triphosphates helps gemcitabine triphosphate to compete with deoxycytidine triphosphate (dCTP) to be incorporated into DNA. DNA synthesis is halted, since only one additional nucleotide can be added to a DNA strand after gemcitabine is incorporated.^[1]^[2]
Route: IV
Extravasation: irritant or neutral, depending on reference

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.^[1]

Diseases for which it is established (work in progress)

Diseases for which it is used

Patient drug information

History of changes in FDA indication

Breast cancer

2004-05-19: New FDA indication in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated. (Based on Albain et al. 2008)

Non-small cell lung cancer

1998-08-25: Indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer. (Based on Cardenal et al. 1999 & Sandler et al. 2000)

Ovarian cancer

2006-07-14: FDA approved in combination with carboplatin for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum based therapy. (Based on AGO-OVAR 2.5)
2010-03-19: New FDA indication for ovarian cancer in combination with carboplatin. (Prior exposure requirement removed; no supporting studies are cited)
2013-05-07: FDA indication revised: in combination with carboplatin, for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. (Prior exposure requirement restored; no supporting studies are cited)

Pancreatic cancer

1996-05-15: Initial FDA approval for first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. (Based on Burris et al. 1997)
1996-05-15: Initial FDA approval for patients with adenocarcinoma of the pancreas previously treated with 5-FU. (Based on Rothenberg et al. 1996a)

History of changes in EMA indication

The approval of this drug pre-dates the EMA.

1995-12-01: EURD

History of changes in PMDA indication

2006-06-15: New additional indication for biliary tract cancer.
2008-11-25: New additional indication for the treatment of urothelial carcinoma.
2010-02-05: New additional indication and a new dosage for the treatment of inoperable or recurrent breast cancer.
2011-02-23: New additional indication and a new dosage for the treatment of ovarian cancer which has progressed after cancer chemotherapy.
2013-02-21: New additional indication and a new dosage for the treatment of relapsed or refractory malignant lymphoma.

Also known as

Code name: LY-188011
Generic name: difluorodeoxycytidine hydrochloride, gemcitabine hydrochloride
Brand names: Gemcite, Gemzar, Infugem

References

[insert-1] 1.0 ^1.1 ^1.2 Gemcitabine (Gemzar) package insert

[2] Gemcitabine (Gemzar) package insert (locally hosted backup)

[3] Gemcitabine (Gemzar) patient drug information (Chemocare)

[4] Gemcitabine (Gemzar) patient drug information (UpToDate)

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