The benefit of clinical benefit: a European perspective.

Although the ultimate aim of treating the cancer patient is cure, in most metastatic solid tumors this, unfortunately , can only infrequently be achieved with chemo-therapy. However, potential benefits such as palliation of symptoms or prolongation of survival, are other reasons for using chemotherapy for solid tumors. For the latter, assessment is relatively simple and hardly subject to discussion. However, how can we most appropriately evaluate other potential benefits? Most medical oncologists will be familiar with the use of objective tumor regression to establish response. The measurement of response has clearly improved since the WHO in 1979 [1] issued its handbook for reporting results of cancer treatment. Even the quite straightforward tumor response criteria given in these guidelines have recently appeared limited. With the introduction of sophisticated techniques such as CT scan and MRI it has become possible to describe response in greater detail. This detailed information may well be the reason why over the years response to chemotherapy seemed to decrease while treatment remained unchanged [2]. Moreover, despite the amount of information presently available, determination of response suffers from interobserver variability. With the recent advent of reviewing the objective responses reported in clinical trials with new drugs it has become apparent, that in their enthusiasm about the activity of the new drugs, investigators overestimate the clinical response obtained. In other words, reports of even objective tumor regressions should be interpreted with caution. Another limitation to assessment of objective regression is that for many diseases even objective regression of disease is not appropriately reflected in a prolongation of survival. The justification for nevertheless applying chemotherapy in these cases is that most medical oncologists believe that objective tumor regression also results in a decrease of tumor-related symptoms. Therefore, additional tools for properly investigating the palliation of symptoms are of importance. For many years quality-of-life assessment with all of its limitations, has been used for this purpose. In this issue of Annals of Oncology Rothenberg et al. [3] report on a phase II trial of gemcitabine in patients with refractory pancreatic cancer using the newly introduced 'clinical benefit response' that is presently under consideration by regulatory authorities for drug registration purposes. Despite the fact that objective tumor regression was scarcely mentioned, the authors report that a considerable number of patients benefited from treatment in other respects. The use of clinical benefit response as an endpoint of phase II studies is new and …