TAXOL TM DEVELOPMENT
Summary:-
In 1958 the U.S. National Cancer Institute (NCI) initiated a programme to screen 35,000 plant species for anti-cancer activity.
1962 As part of the programme, the U.S forest service collected Pacific yew bark and shipped it to the NCI for study. Drs Monroe Wall and M.C Wani of Research Triantle Institute, North Carolina, subsequently found that extract of the bark had anti-tumour activity.
In 1971 Drs Wall and Wani identified compound 17, the active ingredient in the bark, as paclitaxel. Development was later suspended because experimental models did not show superior activity and there were problems with procuring, extracting and processing paclitaxel.
1979 Paclitaxel’s unique mechanism of action (tubulin polymerisation) was identified by Susan Horwitz, Phd at Albert Einstein collage of medicine, New York. Paclitaxel prevented cell division by promoting the assembly while inhibiting the disassembly of micro-tubules.
1983 The NCI sponsored phase I clinical trials of paclitaxel against numerous cancers. Allergic reactions, attributed to the solvent Cremaphor EL in the formula, caused some trials to be discontinued and others to be delayed. Phase II trials began in 1985 and phase III trials in 1990.
1989. Researchers at John Hopkin’s Oncology centre reported 30 percent response rate in patients with advanced ovarian cancer who receive paclitaxel. Supply shortages still hindered drug development. The NCI issued an open invitation to pharmaceutical companies to compete for the right to be its commercial partner in developing Taxol TM.
-First-line ovarian combination
-Metastatic breast cancer
-Non-small cell lung cancer
In 1991 after being selected by the NCI, Bristol-Myers Squibb signed a Co-operative Research and Development Agreement (CRADA) with the NCI to speed up the development of paclitaxel. BMS made this drug its number one R&D priority and signed agreements with more than a dozen collaborators to develop alternative sources of paclitaxel.
1992 Bristol-Myers Squibb filed a new drug application for Taxol TM 18 months after signing the CRADA and two years earlier than expected. On 29th December 1992, Taxol TM received initial clearance from the U.S Food and Drug Administration (FDA) for use after failure of first-line or subsequent chemotherapy for Metastatic carcinoma of the ovary.
In 1994 the use of semisynthetic Taxol TM manufactured from renewable sources was developed. The EU recommended the member states approve this semisynthetic alternative. In 1995 Taxol TM was approved in the U.K for the treatment of Metastatic carcinoma of the breast in patients who have failed, or are not candidates for, standard anthracycline containing therapy.
In 1996 a study published in the New England Journal of Medicine showed that survival time for women with advanced ovarian cancer is extended by 50 percent over standard therapy when they are given first line treatment with a Taxol TM cisplatin combination. Consequently later that same year Taxol TM received its licence in the UK for the primary treatment of carcinoma of the ovary in combination with cisplatin, in patients with advanced disease or residual disease (<1 cm) after initial laparotomy.
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