Quest Goes on for All-Round Platinum Cancer Drug June 12, 2001 04:21 AM ET
By Sara Marani LONDON (Reuters) - Precious metal platinum has long adorned the wealthy as jewelry, but its unique chemical properties also make it key for cancer treatment and scientists are working on a new class of drugs that may fight more cancers than ever before. While platinum has several industrial applications, it is also one of the most successful metals in medicine, generating an $800 million market and spurring scientists to explore other areas and other metals in the hope of more fantastic finds. "Platinum has attracted the active interest of more distinguished scientists than any other chemical element," Edward Haslam, chief executive of South African platinum producer Lonmin Plc recently told industry experts gathered in London for the annual Platinum Week. Scientists have been experimenting with the medicinal properties of metal compounds for centuries but it was only in the early 1970s that researcher Barnett Rosenberg discovered that a simple platinum-based compound prevented bacteria from dividing normally. He wondered whether the compound had a similar effect on cancer cells and subsequent tests showed it was indeed biologically active -- until this time, inorganic compounds had never been employed successfully as anti-cancer agents. SUCCESS STORIES There are two main platinum-based anti-cancer drugs -- cisplatin and carboplatin -- which are seen as the most effective curative treatments for many cancers, but are particularly effective for treating solid tumors such as testicular and ovarian cancers. Both are used in chemotherapy -- in the form of a clear fluid given as an intravenous drip -- to slow or halt the growth of cancer cells by binding to DNA and interfering with its repair mechanism, thereby leading to cell death. But they have major side-effects, including the destruction of normal body cells, kidney damage and serious damage to bone marrow and some cancers quickly develop resistance to them -- and this is what scientists are trying to improve. "One of the main areas of development is the issue of side effects. Efforts are going on to try to find more user-friendly versions that are still as active against the tumors of the type of cancer that these drugs are used against," said Dr. Lloyd Kelland at the Institute of Cancer Research in London. "The main problem with cisplatin is damage to the kidney and it causes a lot of sickness. The other important fact about cisplatin and carboplatin is that the two are not equally effective against all types of cancer," he added. "They are very effective against some types (of cancer), so the other push is to find new versions which have a broader activity and start to become active in some of the more common cancers like breast cancer and lung cancer." Cancer caused 12 percent of the 52 million deaths worldwide in 1997 and was the third leading killer after infectious and parasitic diseases and coronary and heart diseases, according to the World Health Organization. Only a third of all cancer cases can be cured with early detection and effective treatment. Lung cancer was the leading cause of deaths from the disease, killing 1.1 million people in 1997, while breast cancer caused 385,000 deaths. Tens of thousands of women worldwide are affected by ovarian cancer with its high mortality rate, and in the UK it affects more than 6,000 women a year, with 4,800 deaths. Testicular cancer, meanwhile, is relatively rare, with around 1,400 new cases every year in the UK, and is now curable in over 90 percent of cases thanks to platinum-based therapy. SELECTIVE SUCCESS So the question baffling the scientists is why the platinum-based drugs are so effective and totally cure certain kinds of cancers and not others. They actually stop some cancers and for example, to cure testicular cancer just a couple of courses of therapy over a few months is enough. "Our long-term goal is to get something with broader activity," explained Kelland. "Why is cisplatin effective against ovarian cancer but not against lung cancer? What's the underlying reason for that? Why is lung cancer unresponsive to these drugs? If we can understand that then we might be able to find ways to overcome it. It's a tantalizing sort of drug, working against some cancers but it's not universal." Cancer is such a widespread killer that celebrities are queuing up to lend their names to raise awareness of the disease -- the latest being Spice Girl Mel C who is teaming up with the UK's Roy Castle Lung Cancer Foundation to spearhead a national campaign aimed at primary school children. At the UK-based Cancer Research Campaign (CRC), initial clinical trials are under way on projects for bladder cancer and others with platinum-based drugs -- but the projects are in collaboration with companies and it's all confidential. "Initially you're just testing all cancers -- patients that have had several other treatments and their disease is resistant to all standard treatments," said Dr. Luisa Sena of the CRC's drug development office. "You try to find out what the side effects are and then you would test on patients with tumors -- based on lab data and the patients' reactions you have some indication that it's going to be efficient. To get to phase III is extremely promising." In fact, there is a platinum-based anti-cancer drug currently in phase III clinical trials sponsored by pharmaceuticals company AstraZeneca, called ZD0473 -- being tested by Canadian company AnorMED which researches and licenses metal-based therapeutic products. "AstraZeneca plans to develop ZD0473 as the "gold standard" platinum drug," said AnorMED CEO Mike Abrams. "Our in-house focus is on the development of...treatment of inflammation, cancer and HIV infection." ZD0473 has shown no nerve or kidney toxicity, and there is evidence of anti-tumor activity. ZD0473 was designed to overcome the limitations of cisplatin and carboplatin after it was found many tumors initially respond to platinum-based therapy, but then resistance can emerge and the disease recurs. Research is also under way to find more user-friendly ways to administer the drugs, as tablets or capsules rather than as a drip, so that they can be given on an outpatient basis. Work is also continuing on other metals for anti-cancer drugs -- the use of titanium complexes is at the clinical trials stage for breast and gastro-intestinal cancers, but liver damage is proving a major side effect. Gold complexes are also shown to have anti-cancer properties, but are too toxic for clinical use. -- The silver-list is a moderated forum for discussion of colloidal silver. To join or quit silver-list or silver-digest send an e-mail message to: [email protected] -or- [email protected] with the word subscribe or unsubscribe in the SUBJECT line. To post, address your message to: [email protected] Silver-list archive: http://escribe.com/health/thesilverlist/index.html List maintainer: Mike Devour <[email protected]>
