Dose response and dose intensity

The strategy of therapeutic dose intensification in oncology has been largely driven by the incomplete chemotherapy sensitivity exhibited by many tumours. Experimental evidence suggests that the drug resistance of cancer cells is often relative; it can be overcome by exposing the 'resistant' cell to higher concentrations of the drug to which it has become 'resistant'. In most laboratory models, extreme degrees of dose escalation are needed to overcome drug resistance.

The concept of dose intensity takes into account time variables. Thus a regimen might be intensified either by increasing the dose or by abbreviating the inter-treatment interval. The biological impact of these two strategies may be very different.

There is a distinction between maintenance of a standard dose and true dose intensification: the shape of the dose-response curve may not be flat i.e. the mathematical relationship between dose and response may vary at different points. It is possible that dose escalation may increase anti-tumour activity only up to a certain point, after which the dose-response curve 'flattens' and further dose increases will be futile.

Results of studies indicate that arbitrary dose reduction should be avoided, and suggest that clinicians should consider use of prophylactic antibiotics, haematopoietic growth factors, etc. in situations where neutropenia and its complications threaten to undermine timely delivery of potentially curative chemotherapy.

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