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Pyrimidine analogues and fluoropyrimidinesIn useSyntheticNeeds review

Gemcitabine

Also known as 2',2'-difluorodeoxycytidine, dFdC, LY188011, Gemzar

A deoxycytidine analogue with two fluorine atoms in the sugar ring, given by injection. A current US label lists ovarian, breast, non-small cell lung and pancreatic cancer.

From discovery to approval

  1. c. 1990 · Earliest report found

    The earliest report found that names gemcitabine is a 1990 Cancer Research paper (by Hertel and colleagues), which says the compound had been synthesised and evaluated in tumour models. A 1988 paper by the same first author, in the Journal of Organic Chemistry, is titled as concerning the synthesis of difluororibofuranosyl nucleosides (title only).[2][3][4]

  2. 1996-05-15 · FDA regular · 6 years after first description

    First-line treatment of patients with advanced (nonresectable stage II or III) or metastatic (stage IV) adenocarcinoma of the pancreas (letter text; it adds that gemcitabine is indicated for patients previously treated with 5-FU). The letter has no accelerated-approval wording; type 'regular' is an inference.[5]

How it works

Nucleoside kinases convert it to a diphosphate, which inhibits ribonucleotide reductase and lowers dCTP, and a triphosphate, which competes with dCTP for incorporation into DNA. After incorporation one more nucleotide is added and DNA synthesis stops, leading to apoptotic cell death.[1]

Where it came from and why

The 1990 abstract reports that growth inhibition of human leukaemia cells in culture led to in vivo testing; the compound was more active than cytarabine in murine solid tumour models. The reason it was first synthesised was not found in a source read.

Cancers

  • Pancreatic cancer

    The current US label lists pancreatic cancer; a randomised trial of 126 patients with advanced symptomatic disease compared gemcitabine with fluorouracil.[6]

  • Non-small cell lung cancer

    The current US label lists first-line use with cisplatin in inoperable locally advanced or metastatic non-small cell lung cancer.[1]

  • Ovarian cancer

    The current US label lists use with carboplatin in advanced ovarian cancer that relapsed at least 6 months after platinum-based therapy.[1]

  • Breast cancer

    The current US label lists use with paclitaxel for first-line treatment of metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were contraindicated.[1]

  • Bladder cancer

    Gemcitabine plus cisplatin was compared with MVAC in advanced or metastatic urothelial carcinoma in a phase III trial (not a listing in the label read).[7]

  • Biliary tract cancer

    Cisplatin plus gemcitabine was compared with gemcitabine alone in locally advanced or metastatic biliary tract cancer in a phase 3 trial (not a listing in the label read).[8]

Worth knowing

  • In the 1990 evaluation, gemcitabine showed good to excellent activity in eight of eight murine tumour models, while cytarabine was substantially less active or inactive in the same models.[2]
  • A 1995 review says gemcitabine is transported better, phosphorylated more efficiently and eliminated more slowly than cytarabine, and proposes this may explain why it is active in solid tumours while cytarabine is not.[4]
  • In a 1997 trial in advanced pancreatic cancer, median survival was 5.65 months with gemcitabine and 4.41 months with fluorouracil (P = .0025); clinical benefit response was 23.8% versus 4.8% (P = .0022).[6]
  • A 2000 trial found overall survival similar for gemcitabine plus cisplatin and MVAC in advanced bladder cancer (hazard ratio 1.04, 95% CI 0.82 to 1.32), with a better safety profile for the gemcitabine regimen.[7]
  • The Drugs@FDA history for NDA 020509 lists the original approval on 15 May 1996.[9]

On this site

References

  1. Hospira, Inc. Gemcitabine injection, solution: prescribing information. DailyMed, set ID dc02a23b-3ff9-4441-aa91-8e9e629a7315, published 29 April 2026. Source
  2. Hertel LW, Boder GB, Kroin JS, Rinzel SM, Poore GA, Todd GC, et al. Evaluation of the antitumor activity of gemcitabine (2',2'-difluoro-2'-deoxycytidine). Cancer Res. 1990;50(14):4417-22. PubMed
  3. Hertel LW, Kroin JS, Misner JW, Tustin JM. Synthesis of 2-deoxy-2,2-difluoro-D-ribose and 2-deoxy-2,2'-difluoro-D-ribofuranosyl nucleosides. J Org Chem. 1988;53(11):2406-9. DOI
  4. Plunkett W, Huang P, Gandhi V. Preclinical characteristics of gemcitabine. Anticancer Drugs. 1995;6 Suppl 6:7-13. PubMedDOI
  5. US Food and Drug Administration. Approval package, Gemzar (gemcitabine hydrochloride) for Injection, NDA 20-509, Eli Lilly and Company; approval letter dated 15 May 1996 (scanned image document in the Drugs@FDA archive). Source
  6. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403-13. PubMedDOI
  7. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. 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. 2000;18(17):3068-77. PubMedDOI
  8. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-81. PubMedDOI
  9. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020509 (gemcitabine; Gemzar). Page read 2026-10-26. Source
  10. Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin Oncol. 1995;22(4 Suppl 11):3-10. PubMed