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Microtubule-targeting agentsIn useDerivative of an earlier drug

Docetaxel

Also known as Taxotere, RP 56976, NSC 628503

A semisynthetic taxane given by infusion, made from a precursor extracted from yew needles. Its US label lists breast, non-small cell lung, prostate, gastric and head and neck cancers.

From discovery to approval

  1. 1991 · Earliest report found

    Docetaxel (RP 56976, Taxotere) was made by semisynthesis from 10-deacetylbaccatin III, a noncytotoxic precursor extracted from the needles of the European yew, Taxus baccata. The earliest papers found are three 1991 reports; no source read dates the first synthesis.[2][3][4][5][6][7][8][9][10][11]

  2. 1995-11-27 · EMA regular

    Marketing authorisation issued 27 November 1995 (EMEA/H/C/000073). The EPAR page lists current indications in breast, non-small-cell lung, prostate, gastric and head and neck cancers; the original 1995 wording is not given there. The page does not mention a conditional or exceptional-circumstances authorisation; the type regular is an inference from that absence.[12]

  3. 1996-05-14 · FDA accelerated

    Locally advanced or metastatic breast cancer that has progressed during anthracycline-based therapy or has relapsed during anthracycline-based adjuvant therapy. The letter says the application was reviewed according to the accelerated approval regulations and approved under 21 CFR 314.510, and acknowledges the sponsor's commitment to complete four controlled clinical trials to verify and describe clinical benefit. The letter is dated 14 May 1996 and approval is effective on that date.[9]

  4. 1998-06-22 · FDA converted

    Treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy (NDA 20-449/S-005); S-006, approved in the same letter, changes the label to the three-day corticosteroid premedication regimen. The letter says the NDA was approved under 21 CFR 314.510 and that approval of S-005 fulfills the commitments made under that regulation; it does not use the word converted.[11]

  5. 2002-11-27 · FDA regular

    In combination with cisplatin, unresectable, locally advanced or metastatic non-small cell lung cancer in patients who have not previously received chemotherapy for this condition (NDA 20-449/S-018). The type regular is an inference: no accelerated-approval wording was found.[13]

  6. 2004-05-19 · FDA regular

    In combination with prednisone for patients with androgen independent (hormone refractory) metastatic prostate cancer; the letter is dated by its electronic signature (5/19/04) and states approval is effective on the date of the letter. The letter contains no accelerated-approval (subpart H) wording; the type 'regular' is an inference from that absence.[14]

  7. 2004-08-18 · FDA regular

    In combination with doxorubicin and cyclophosphamide, adjuvant treatment of patients with operable node-positive breast cancer (NDA 20-449/S-029); the letter is dated by its electronic signature (8/18/04). The type regular is an inference: no accelerated-approval wording was found.[15]

How it works

The label says docetaxel disrupts the microtubular network: it binds free tubulin, promotes assembly into stable microtubules and inhibits their disassembly, producing nonfunctional microtubule bundles and inhibiting mitosis. Its binding does not alter the number of protofilaments in the microtubules.[1]

Where it came from and why

A 1994 review says taxol extraction from yew bark is expensive, difficult and damaging to the trees, so alternative sources were studied. A 1993 review adds that the preclinical profile showed higher antitumour activity than taxol with a comparable toxicity profile.

Docetaxel was among the compounds prepared from a renewable taxane precursor during the search for alternatives to bark extraction. A 1994 review says that extracting taxol from yew bark is expensive, difficult and damaging to the trees, and that one of the most promising alternatives was semisynthesis from 10-deacetylbaccatin III, a renewable precursor in the needles of the European yew, Taxus baccata [6].

In a 1991 study of taxol analogues, N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol, named taxotere, was one of the most potent in inhibiting microtubule disassembly and murine P388 leukaemia cells, and was selected for evaluation as a potential anticancer agent [2]. A second 1991 report found that, like taxol, it promoted microtubule assembly in vitro [3], and a third found activity in 9 of 11 transplantable mouse tumour models tested [4].

Phase I trials were published in 1992 and 1993 [7] [8]. On 14 May 1996 the FDA approved docetaxel under its accelerated approval regulations for locally advanced or metastatic breast cancer that had progressed during, or relapsed after, anthracycline-based therapy [9]. An FDA letter of 22 June 1998 states that approval of a supplement for breast cancer after failure of prior chemotherapy fulfilled the commitments made under that regulation [11].

Cancers

  • Breast cancer

    The US label lists locally advanced or metastatic breast cancer after failure of prior chemotherapy and, with doxorubicin and cyclophosphamide, adjuvant treatment of operable node-positive breast cancer.[1]

  • Non-small cell lung cancer

    The label lists single-agent treatment after failure of platinum-based chemotherapy, and treatment with cisplatin of unresectable, locally advanced or metastatic disease not previously treated with chemotherapy.[1]

  • Prostate cancer

    The label lists treatment with prednisone of metastatic castration-resistant prostate cancer.[1]

  • Gastric adenocarcinoma

    The label lists treatment with cisplatin and fluorouracil of advanced gastric adenocarcinoma, including the gastroesophageal junction, in patients not previously treated for advanced disease.[1]

  • Head and neck cancer

    The label lists induction treatment, with cisplatin and fluorouracil, of locally advanced squamous cell carcinoma of the head and neck.[1]

Family and partners

Derived from: Paclitaxel

Worth knowing

  • In mice, docetaxel produced a 3.0 log10 tumour cell kill in B16 melanoma at the maximum tolerated dose, against 1.1 log10 for taxol in the same trial, as reported by the authors of the 1991 study.[4]
  • A 1991 report found docetaxel 2.5-fold more potent than taxol as an inhibitor of cell replication in two cell lines, and at least 5-fold more potent in taxol-resistant cells.[3]
  • The 1996 FDA letter approved docetaxel under the accelerated approval regulations and acknowledged the sponsor's commitment to complete four controlled trials in breast cancer to verify and describe clinical benefit.[9]
  • A 1995 review reports that in phase I studies the dose-limiting toxicity of docetaxel was neutropenia, and that the recommended phase II dose was 100 mg/m2 as a 1-hour infusion every 3 weeks.[16]
  • The label notes that docetaxel's binding to microtubules does not alter the number of protofilaments, a feature it says differs from most spindle poisons in clinical use.[1]

On this site

References

  1. Mylan Institutional LLC. Docetaxel injection: prescribing information. DailyMed, set ID 2fb017fd-e55e-43ef-9024-07f2d412b37b, published 5 October 2026. Source
  2. Guéritte-Voegelein F, Guénard D, Lavelle F, Le Goff MT, Mangatal L, Potier P. Relationships between the structure of taxol analogues and their antimitotic activity. J Med Chem. 1991;34(3):992-8. PubMedDOI
  3. Ringel I, Horwitz SB. Studies with RP 56976 (taxotere): a semisynthetic analogue of taxol. J Natl Cancer Inst. 1991;83(4):288-91. PubMedDOI
  4. Bissery MC, Guénard D, Guéritte-Voegelein F, Lavelle F. Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue. Cancer Res. 1991;51(18):4845-52. PubMed
  5. Lavelle F, Gueritte-Voegelein F, Guenard D. [Taxotere: from yew's needles to clinical practice]. Bull Cancer. 1993;80(4):326-38. PubMed
  6. Guéritte-Voegelein F, Guénard D, Dubois J, Wahl A, Potier P. [Chemical and biological studies on Taxol (Paclitaxel) and Taxotere (Docetaxel), new antineoplastic agents]. J Pharm Belg. 1994;49(3):193-205. PubMed
  7. Pazdur R, Newman RA, Newman BM, Fuentes A, Benvenuto J, Bready B, et al. Phase I trial of Taxotere: five-day schedule. J Natl Cancer Inst. 1992;84(23):1781-8. PubMedDOI
  8. Burris H, Irvin R, Kuhn J, Kalter S, Smith L, Shaffer D, et al. Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion. J Clin Oncol. 1993;11(5):950-8. PubMedDOI
  9. U.S. Food and Drug Administration. Taxotere (docetaxel) for injection concentrate, NDA 20-449: approval letter of 14 May 1996 within the historical CDER review file posted on Drugs@FDA. Source
  10. Wani MC, Horwitz SB. Nature as a remarkable chemist: a personal story of the discovery and development of Taxol. Anticancer Drugs. 2014;25(5):482-7. PubMedDOI
  11. U.S. Food and Drug Administration. Supplemental NDA approval letter, Taxotere (docetaxel) for Injection Concentrate, NDA 20-449/S-005 and S-006, Rhone-Poulenc Rorer Pharmaceuticals, Inc.; letter dated June 22, 1998. Source
  12. European Medicines Agency. Taxotere (docetaxel): EPAR product page (EMEA/H/C/000073); page shows last update 22 October 2026. Read 2026-10-29. Source
  13. U.S. Food and Drug Administration. Supplemental NDA approval letter, Taxotere (docetaxel), NDA 20-449/S-018, Aventis Pharmaceuticals; electronic signature dated 11/27/02. Source
  14. US Food and Drug Administration. Supplemental NDA approval letter, Taxotere (docetaxel), NDA 20-449/S-028, Aventis Pharmaceuticals; electronic signature dated 5/19/04. Source
  15. U.S. Food and Drug Administration. Supplemental NDA approval letter, Taxotere (docetaxel), NDA 20-449/S-029, Aventis Pharmaceuticals; electronic signature dated 8/18/04. Source
  16. Cortes JE, Pazdur R. Docetaxel. J Clin Oncol. 1995;13(10):2643-55. PubMedDOI