The story of temozolomide
The story of the brain tumour drug temozolomide is a fantastic example of how the public’s generous support of Cancer Research UK has directly benefited the lives of people with cancer.
Cancer Research UK led the development of temozolomide. From early pioneering lab work, to the discovery, development and first clinical trials of the drug in people with cancer, our scientists were involved every step of way.
Watch a video featuring Professor Malcolm Stevens, now at the University of Nottingham, who led the pioneering work on temozolomide:
The story of temozolomide started in the late 1970s at Aston University in Birmingham, where Professor Malcolm Stevens led a team of Cancer Research UK-funded researchers.
Building on the earlier work of another Cancer Research UK scientist, Professor Tom Connors1, they carried out innovative lab experiments to develop new drug prototypes. And they tested the potential of these novel molecules to treat cancer.
It took almost a decade of painstaking work and rigorous testing in the lab, but by 1987 they’d made a new molecule that looked like a promising candidate2. This later became known as temozolomide.
Having supported the laboratory work behind temozolomide, Cancer Research UK was again instrumental in the next phase of the drug’s journey.
Earlier in the 1980s, three of our scientists founded our internationally recognised Phase I/II Clinical Trials Committee, the forerunner to our current Drug Development Office. The committee’s aim was simple – to improve the transition of potential new cancer treatments from the lab to patients for first testing in trials.
The exciting work of Professor Stevens and his colleagues convinced the Committee to set up the first ever trial of temozolomide in a small group of cancer patients at Charing Cross Hospital in London.
The results of this early-stage trial were very promising3, encouraging Cancer Research UK to support further clinical trials in larger groups.
Temozolomide was first produced in the relatively small quantities needed for lab work at Aston University. Once clinical trials started, demand for the drug increased dramatically.
Researchers at our Formulation Unit at The University of Strathclyde developed a process to make bigger batches of temozolomide. And they manufactured and supplied the drug in capsules to treat patients in clinical trials.
The larger clinical trials of temozolomide were also successful4. As well as extending survival, patients with glioblastoma benefited mentally and physically from treatment with temozolomide.
Based on these results, the charity's commercial and development arm, Cancer Research Technology, licensed the drug to the pharmaceutical company Schering-Plough. The company then funded a series of trials that led to the approval of temozolomide.
Worldwide sales of temozolomide have now reached $1 billion. Because of our unique partnership with Schering-Plough, we receive a royalty on these sales – we devote these funds to new work into the prevention, diagnosis and treatment of cancer.
Temozolomide continues to benefit more and more people each year. And our scientists are now testing the drug for treating other types of cancer.
The discovery and development of temozolomide would not have been possible without Cancer Research UK – with the continued support of the public we will develop the life-saving treatments of tomorrow.
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- Audette RC, Connors TA, Mandel HG, Merai K, Ross WC. Studies on the mechanism of action of the tumour inhibitory triazenes. Biochem Pharmacol 1973; 22(15):1855-64
- Stevens, M. F. et al. Antitumor activity and pharmacokinetics in mice of 8-carbamoyl-3-methyl-imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (CCRG 81045; M & B 39831), a novel drug with potential as an alternative to dacarbazine. Cancer Res 1987 47:5846-52
- Newlands, E. S. et al. Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). Br J Cancer. 1992 65: 287-91
- Bower M, Newlands ES, Bleehen NM, Brada M, Begent RJ, Calvert H, Colquhoun I, Lewis P, Brampton MH. Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma. Cancer Chemother Pharmacol 1997; 40: 484–488