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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(02): 260-263
DOI: 10.4103/ijmpo.ijmpo_139_20
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History of Paclitaxel and Oral Paclitaxel – Clinical Data and Future

Ganesh Divekar
Clinical Operations and Medical Services, SIRO Clinpharm Pvt. Ltd., Thane, Maharashtra, India
,
Bharat Bhosale
Department of Medical Oncology, Bombay Hospital and Medical Research Centre, Mumbai, Maharashtra, India
Department of Medical Oncology, Vedant Hospital, Thane, Maharashtra, India
Department of Medical Oncology, Jaslok Hospital and Research Centre, Mumbai, Maharashtra, India
Department of Medical Oncology, Sir H N Reliance Foundation Hospital and Research Centre, Mumbai, Maharashtra, India
Department of Medical Oncology, SL Raheja Hospital, Mumbai, Maharashtra, India
,
Padmaj Kulkarni
Department of Medical Oncology, Deenanath Mangeshkar Hospital, Pune, Maharashtra, India
› Author Affiliations Financial support and sponsorship Nil.
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Paclitaxel

The most known natural source cancer drug is paclitaxel, which is derived from the tough protective outer sheath of the trunk and branches (referred as bark) of the Pacific yew tree (Taxus brevifolia).[1] Paclitaxel has demonstrated a wide spectrum of antitumor activity as a single agent and also in combination with other chemotherapeutic agents as part of combination regimens.[2] It is used extensively in the treatment of advanced carcinomas of the breast, ovarian cancer, nonsmall cell lung cancer, and other solid tumors.

Although discovered in 1962, development toward the clinic was slow, mainly due to the difficulties in harvesting paclitaxel and due to the complexities involved in synthesizing the compound. Polysciences, Inc. was the first company to achieve large-scale production of paclitaxel. Clinical trials with paclitaxel were initiated when it was made possible to derive 10-deacetylbaccatin III (a precursor of paclitaxel), from the plant which many people have it in their gardens, namely Taxus baccata.[1]

Paclitaxel also posed other challenges during its development. Due to its hydrophobic nature, formulation which can be administered to human beings was difficult. When the bulk drug was suspended to have a solution, initial cytotoxic activity was noted. Later to make the formulation acceptable for human use, paclitaxel was mixed with an ethanol, cremophor, and saline solution in the ratio 5:5:90 to a concentration of 0.3–0.6 mg/mL. With this, the intraperitoneal activity was maintained at the levels, which were noted earlier.[1]

In 1984, the National Cancer Institute initiated first in human clinical trials of paclitaxel wherein patients with various cancer types. The spur in clinical demand followed the report wherein investigators at Johns Hopkins reported partial or complete response in 30% of patients with advanced ovarian cancer in 1989.[1]

In December 1992, the United States Food and Drug Administration (US-FDA) approved the therapeutic use of paclitaxel in patients with ovarian cancer. In 1994, postconclusive evidence on the effectiveness of paclitaxel against advanced breast cancer, US-FDA approved paclitaxel in the treatment of breast cancer.[1]



Publication History

Received: 07 April 2020

Accepted: 23 April 2020

Article published online:
23 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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  • References

  • 1 Available from: dtp.cancer.gov/timeline/flash/success_stories/S2_Taxol.htm. [Last accessed on 2020 Mar 22]
  • 2 Crown J, O’Leary M. The taxanes: An update. Lancet 2000; 355: 1176-8
    CrossrefPubMedGoogle Scholar
  • 3 Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL. et al. Hypersensitivity reactions from taxol. J Clin Oncol 1990; 8: 1263-8
    CrossrefPubMedGoogle Scholar
  • 4 Rowinsky EK, Donehower RC. Paclitaxel (taxol). N Eng J Med 1995; 332: 1004-14
    CrossrefPubMedGoogle Scholar
  • 5 Finley RS, Rowinsky EK. Patient care issues: The management of paclitaxel-related toxicities. Ann Pharmacother 1994; 28: S27-30
    CrossrefPubMedGoogle Scholar
  • 6 Windebank AJ, Blexrud MD, de Groen PC. Potential neurotoxicity of the solvent vehicle for cyclosporine. J Pharmacol Exp Ther 1994; 268: 1051-6
    PubMedGoogle Scholar
  • 7 Waugh WN, Trissel LA, Stella VJ. Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers. Am J Hosp Pharm 1991; 48: 1520-4
    PubMedGoogle Scholar
  • 8 Hidalgo M, Aylesworth C, Hammond LA, Britten CD, Weiss G, Stephenson Jr. J. et al. Phase I and pharmacokinetic study of BMS-184476, a taxane with greater potency and solubility than paclitaxel. J Clin Oncol 2001; 19: 2493-503
    CrossrefPubMedGoogle Scholar
  • 9 Dai MS, Chao TC, Chiu CF, Lu YS, Shiah HS, Wu YY. et al. Oral paclitaxel in the treatment of metastatic breast cancer (MBC). J Clin Oncol 2019; 37 (15) 1084
    CrossrefGoogle Scholar
  • 10 Available from: https://www.athenex.com/pipeline/orascovery-platform/. [Last accessed on 17 Apr 2020]
  • 11 Available from: https://clinicaltrials.gov/ct2/show/NCT03326102. [Last accessed on 22 Mar 2020]
  • 12 Umanzor G, Rugo HS, Barrios FJ, Vesallo RH, Chivalan MA, Bejarano S. Oral paclitaxel with encequidar: The first orally administered paclitaxel shown to be superior to IV paclitaxel on confirmed response and survival with less neuropathy: A phase III clinical study in metastatic breast cancer. Presented at the San Antonio Breast Cancer Symposium. San Antonio, Texas: Abstract: GS6-01; 10-14 December 2019
    Google Scholar
  • 13 Walko CM, Lindley C. Capecitabine: A review. Clin Ther 2005; 27: 23-44
    CrossrefPubMedGoogle Scholar
  • 14 Available from: https://www.medscape.com/viewarticle/576969. [Last accessed on 22 Mar 2020]
  • 15 Zhu J, Zeng W, Ge L, Yang X, Wang Q, Wang H. Capecitabine versus 5-fluorouracil in neoadjuvant chemoradiotherapy of locally advanced rectal cancer: A meta-analysis. Medicine (Baltimore) 2019; 98: e15241
    CrossrefPubMedGoogle Scholar
  • 16 Cassidy J, Douillard JY, Twelves C, McKendrick JJ, Scheithauer W, Bustová I. et al. Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes’ C colon cancer: The X-ACT trial. Br J Cancer 2006; 94: 1122-9
    CrossrefPubMedGoogle Scholar