Tailored chemotherapy to equal toxicity: is it possible?

Conventional dosage of chemotherapy based on body surface area in patients with normal organ functions will result in marked interindividual variations in systemic exposure to the cytostatics used. This will result in over- and undertreatment of the individual patient associated with unwarranted toxicity and suboptimal outcome. The intention to modify dosage is motivated by a possible correlation between toxicity and outcome. New dosage strategies with individual tailoring of the therapy should be investigated with the aim of increasing the efficacy of therapy without increasing its toxicity. Pharmacokinetic monitoring using the limited sampling procedure could be one alternative, another toxicity-guided dosage. The dosage scheme used for tailored FEC polychemotherapy (six dose levels), based on therapy to equivalent haematological toxicity, has been clinically applicable in the multicentre setting for both adjuvant and preoperative therapy. In the adjuvant setting it has resulted in the delivery of significantly higher epirubicin and cyclophosphamide doses without increasing acute toxicity to the same extent; in two out of three patients no difference in acute toxicity could be verified for the highest two dose levels compared with the lower dose levels. In short, we could obtain better results with our present arsenal of cytostatics if we used them better.