Platinum Metals Rev., 1995, 39, (2), 63
Platinum Co-ordination Compounds for Cancer Chemotherapy
A new feature of the Seventh International Symposium in the series on Metal Co-ordination Compounds in Cancer Chemotherapy, held in Amsterdam from 1st to 4th March, 1995, was the presentation of the Barnett Rosenberg award for contribution to the field of platinum-based chemotherapy. The recipient of the award, Professor Ken Harrap of the Institute of Cancer Research, London, described to the audience the history of the development of cisplatin and carboplatin and the selection of JM-216 as a candidate for an orally administered agent. He concluded by reporting ongoing work aimed at identifying compounds capable of extending the application of platinum chemotherapy by over-coming the resistance seen to cisplatin and carboplatin. In particular he highlighted the potential of trans compounds, an area which was raised in a number of other presentations on novel compounds.
In presentations on clinical experience with the newer platinum analogues, JM-216 was shown to have myelosuppression as its dose limiting toxicity in a daily × 5 schedule, and it has now entered Phase II trials in Europe for the treatment of lung cancer. Oxaliplatin, an analogue which has been in trials for some time now, was shown to offer benefit in colorectal cancer when combined with other drugs and using chronomodulated delivery. Lobaplatin continues to be evaluated in Phase II trials in Europe. In Japan, approval has been sought for the marketing of 254-S which has shown activity in the treatment of head and neck and gastro-intestinal tumours, and a new second generation analogue, TRK-710, has entered Phase I testing.
A debate on the relative merits of cisplatin and carboplatin in the clinic concluded it was clear that carboplatin was preferred in a palliative setting and in high dose treatments. In testicular and good-prognosis ovarian cancer patients, where cisplatin drug combinations are known to produce a high percentage of cures, concern regarding the therapeutic equivalence of carboplatin limits its use as an alternative. The different toxicities of the two drugs give each advantages in particular combinations for specific treatments, and in this context it was noted in several presentations that the combination of carboplatin and paclitaxel (taxol) is showing promise in ovarian and lung cancers. Confirmation of these early results by more definitive studies is eagerly awaited.
Much research is now being devoted to the understanding of cellular control mechanisms involved in cell proliferation and cell death. While it was initially proposed that chemotherapeutic agents capable of influencing these mechanisms might replace the use of cytotoxic therapy, presentations at this symposium suggested that it is more likely that they will be used in combination with cytotoxic compounds, such as the platinum drugs, to increase their effectiveness. It seems likely therefore that the platinum drugs will remain a vital part of cancer chemotherapy and a topic of international interest for some time to come.