Forty years after the accidental discovery of their anti-cancer properties, platinum based compounds represent one of the most important classes of oncology drugs. Platinum compounds are effective in treating a wide array of malignancies including lung, ovarian and colorectal cancers. Cisplatin was the first approved platinum drug (1978) followed by carboplatin (1989) and oxaliplatin (2002), which together generated annual worldwide sales of approximately $3 billion in 2007. These drugs exert their antitumor activity by binding to DNA and interfering with DNA replication, ultimately leading to cell death.
Despite their impressive activity, platinum drugs suffer from two primary drawbacks. The first drawback is the appearance of undesirable side effects and toxicities. Cisplatin often leads to kidney toxicity, while carboplatin and oxaliplatin often lead to bone marrow and nerve toxicities. The most urgent safety issue is the nerve toxicity caused by the use of oxaliplatin in colorectal cancer, as it sometimes forces physicians to stop the administration of the drug. The second drawback of platinum compounds is the emergence of platinum resistance in most patients during or following treatment. These patients stop responding to treatment after an initial response within several months of initial treatment. Moreover, some cancers are inherently resistant to platinum even before being exposed to platinum drugs. Fortunately, many resistance mechanisms tumors utilize to block the anti-cancer effect of platinum drugs have now been elucidated, and this knowledge will hopefully provide the basis for the development of the next generation of platinum drugs.
Efforts to develop novel platinum agents are currently very modest, with only a handful of compounds in the clinic. Throughout the 90’s, hundreds of compounds have been screened but this effort resulted in only one approved agent, Sanofi-Aventis’ (SNY) oxaliplatin. Consequently, the pharmaceutical giants abandoned the field, leaving it to smaller companies such as Spectrum (SPPI) and Poniard (PARD). The recent disappointing data from Spectrum’s Satraplatin in prostate cancer only increased the negative sentiment towards experimental platinum compounds. At the moment, Poniard’s picoplatin is the only platinum drug in phase III, with results expected in the middle of next year.
