Pharmacokinetics and cancer: successes, failures and future prospects.

Cancer pharmacokinetics has made an enormous contribution to the development and optimization of cancer therapy. While consolidating its position and subjecting itself to prospective clinical trials in areas of established pharmacology, it needs also to keep constantly on the move in order to respond to the challenging demands of more futuristic approaches. Antibodies, cytokines, nucleic acid drugs and therapeutic genes will be metabolized and excreted and will in addition display special difficulties in terms of tissue and cell uptake. Pharmacokinetic considerations must accompany all new experimental therapies for scientific reasons as well as to fulfil regulatory requirements (Peck et al, 1992). The very latest approaches will understandably be seen by many practising clinicians as science fiction--for example obtaining a genetic fingerprint of a patient's tumour in order to guide corrective therapy, whether it be based on a chemical drug or a replacement gene. But it is from such speculative attempts that the real breakthroughs of the future may follow and pharmacokinetic/pharmacodynamic studies are essential to these efforts. In terms of the role of pharmacokinetics and pharmacodynamics in day to day management of individual patients, we do need to be more pragmatic. We must address tough questions such as: Can the assays be conducted on a routine basis? Do the measurements affect treatment outcome? Are they cost effective? Will they actually be used by clinical and nursing staff in a busy hospital environment? There is ample evidence in the following pages that pharmacokinetics will continue to prove vital to support both routine patient management and the exciting new approaches to cancer therapy.