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Bending the Curve Trial by Trial
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Microtubule-targeting agentsIn useNatural product

Paclitaxel

Also known as Taxol, paclitaxel injection

A taxane given by infusion, first isolated from the bark of the Pacific yew. Its generic US label lists ovarian, breast and non-small cell lung cancers and AIDS-related Kaposi sarcoma.

From discovery to approval

  1. 1971 · First described

    Wani, Wall and colleagues at Research Triangle Institute isolated taxol from Pacific yew bark and published its structure in 1971. Weaver says it had been isolated and named by 1967; Wani and Horwitz say the first yew samples reached the institute in 1964.[2][3][4][5][6][7][8][1]

  2. 1992-12-29 · FDA regular · 21 years after first description

    Paclitaxel (Taxol), NDA 020262, original approval, classed as a new molecular entity with priority review and orphan status in the Drugs@FDA history. The original label and letter are not available there, so the indication at approval is not stated by that source; two reviews describe the 1992 approval as being for refractory ovarian cancer. The type regular is an inference: no accelerated-approval wording was found.[8]

How it works

The label says it promotes the assembly of microtubules from tubulin dimers and stabilises them by preventing depolymerisation, which inhibits the normal dynamic reorganisation of the microtubule network. It also induces abnormal bundles of microtubules throughout the cell cycle.[1]

Where it came from and why

The Pacific yew was one of about 15,000 plant species sampled in a National Cancer Institute and Department of Agriculture screening programme that ran from 1960 to 1981. Yew bark extracts were cytotoxic to cultured human cancer cells, an assay the chemists had asked for extracts of because it correlated with mouse leukaemia activity.

In 1960 the National Cancer Institute began a screening programme for antitumour agents in plants, led by Jonathan Hartwell, with samples supplied by the US Department of Agriculture [2]. In August 1962 the botanist Arthur Barclay and three student assistants collected 650 samples, including Pacific yew in Washington State [2]. The first yew samples reached Research Triangle Institute in 1964, where Monroe Wall and Mansukh Wani isolated about 0.5 grams of taxol from 12 kilograms of dried stem and bark [2]. They published its structure in 1971 [4].

Interest was limited at first. Wani and Horwitz say development stalled for nearly a decade because of modest activity in leukaemia models, poor water solubility and expected supply problems [2]. In 1977 the National Cancer Institute asked Susan Horwitz to study how taxol works, and in 1979 her laboratory reported that it promotes the assembly of microtubules [2] [5].

Weaver dates the first phase I trial to 1984, while Wani and Horwitz describe a pause in trials from 1983 to 1988 after severe hypersensitivity reactions, so the sources disagree on when trials began [3] [2]. Phase I reports from 1986 and 1987 describe treatment-limiting hypersensitivity reactions with a 3-hour schedule [9] and, with premedication and a 6-hour infusion, dose-limiting neurotoxicity and leukopenia [10]. Wani and Horwitz add that the National Cancer Institute awarded a cooperative research and development agreement to Bristol-Myers Squibb [2], and Weaver says the company was selected in 1991 [3]. The FDA approved Taxol for refractory ovarian cancer on 29 December 1992 [2] [8].

Cancers

  • Ovarian cancer

    The generic US label lists subsequent therapy for advanced carcinoma of the ovary, and first-line therapy in combination with cisplatin.[1]

  • Drug-refractory ovarian cancer (phase II)

    A phase II trial gave taxol as a 24-hour infusion to 47 patients with drug-refractory epithelial ovarian cancer; 12 of the 40 evaluable for response (30%) responded.[11]

  • Breast cancer

    The label lists adjuvant treatment of node-positive breast cancer after doxorubicin-containing chemotherapy, and breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy.[1]

  • Metastatic breast cancer (phase II)

    A phase II trial gave taxol 250 mg/m2 as a 24-hour infusion every 21 days to 25 patients with metastatic breast cancer; the objective response rate was 56%, as reported by the authors.[12]

  • Non-small cell lung cancer

    The label lists first-line treatment in combination with cisplatin for patients who are not candidates for potentially curative surgery or radiation therapy.[1]

  • AIDS-related Kaposi sarcoma

    The label lists second-line treatment of AIDS-related Kaposi sarcoma.[1]

Family and partners

Drugs derived from it: Docetaxel, Paclitaxel protein-bound particles (albumin-bound), Cabazitaxel

Worth knowing

  • Weaver says the National Cancer Institute and the Department of Agriculture collected and tested 115,000 extracts from 15,000 plant species between 1960 and 1981.[3]
  • Wani and Horwitz report that about 0.5 grams of taxol was isolated from 12 kilograms of air-dried yew stem and bark, a yield of about 0.004%.[2]
  • Weaver writes that Bristol-Myers Squibb trademarked the name Taxol in 1992 and created the generic name paclitaxel, although the term taxol had appeared in more than 600 manuscripts over 20 years.[3]
  • A 1990 review contrasts taxol with colchicine and the vinca alkaloids: those drugs cause microtubules to depolymerise, whereas taxol induces tubulin polymerisation and forms extremely stable, nonfunctional microtubules.[13]
  • Weaver says at least 30 laboratories worldwide competed to develop a total synthesis of taxol, which was not achieved until 1994 and needs roughly 40 reaction steps; a more practical semisynthetic route became the standard way to produce it.[3]

On this site

References

  1. Hospira, Inc.. Paclitaxel injection: prescribing information. DailyMed, set ID ea28753a-8631-460a-bfdc-b101eb8ac84a, published 3 July 2026. Source
  2. 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
  3. Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014;25(18):2677-81. PubMedDOI
  4. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 1971;93(9):2325-7. PubMedDOI
  5. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature. 1979;277(5698):665-7. PubMedDOI
  6. Oberlies NH, Kroll DJ. Camptothecin and taxol: historic achievements in natural products research. J Nat Prod. 2004;67(2):129-35. PubMedDOI
  7. Wall ME, Wani MC. Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 1995;55(4):753-60. PubMed
  8. U.S. Food and Drug Administration. Drugs@FDA: Approval date(s) and history, letters, labels, reviews for NDA 020262 (paclitaxel; Taxol). Page read 2026-10-29. Source
  9. Kris MG, O'Connell JP, Gralla RJ, Wertheim MS, Parente RM, Schiff PB, et al. Phase I trial of taxol given as a 3-hour infusion every 21 days. Cancer Treat Rep. 1986;70(5):605-7. PubMed
  10. Wiernik PH, Schwartz EL, Strauman JJ, Dutcher JP, Lipton RB, Paietta E. Phase I clinical and pharmacokinetic study of taxol. Cancer Res. 1987;47(9):2486-93. PubMed
  11. McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, et al. Taxol: a unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med. 1989;111(4):273-9. PubMedDOI
  12. Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, et al. Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst. 1991;83(24):1797-805. PubMedDOI
  13. Rowinsky EK, Cazenave LA, Donehower RC. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst. 1990;82(15):1247-59. PubMedDOI