Trial Information

Study on the Influence of Sunitinib and Sorafenib on Fatigue, Quality of Life and Depression in Patients With Metastatic Renal Cell Cancer or GIST

When cure is not longer possible, cancer patients enter the palliative phase. For many types
of cancer several treatment options are available. The goal of this treatment is to prolong
survival, but maintenance or even improvement of quality of life is of equal importance. The
currently available systemic treatment options consist of conventional cytotoxic therapy,
hormonal therapy, immunotherapy and the so-called targeted therapies. Combinations of these
therapies are also being used. Targeted therapy concerns the application of a new class of
drugs that are specifically directed against one or more well-defined molecular targets that
are relevant for carcinogenesis, cell cycle regulation, tumour progression, metastasis,
tumour angiogenesis and/or apoptosis. Today, the most successful drugs in this class are
directed against the vascular endothelial growth factor (VEGF) and the epidermal growth
factor receptor (EGFR). There is an explosive development ongoing in this field and many new
drugs become available that have new targets or inhibit a combinations of targets.
Meanwhile, targeted therapy has shown efficacy in many types of cancer and is registered for
several indications.

The toxicity profile of targeted therapies is still largely unknown, and the aetiology of
many known side effects has not been clarified. This implies that the effective treatment of
side effects is in an early phase of development. Given the impact of side effects on the
quality of life of a patient, increased knowledge on this topic is urgently required.
Currently only a few systematic studies are available that address this issue. At the
moment, three targeted therapies that are directed against VEGF are registered and used in
the Netherlands: Sunitinib (Sutent®) and Sorafenib (Nexavar ®) both oral drugs and
Bevacizumab (Avastin®), an intravenously drug.

In this study we will focus on fatigue, quality of life and depression in patients with
metastatic cancer, treated with Sunitinib and Sorafenib. Fatigue is one of the most
frequent side effects of targeted therapy that are directed against VEGF and that can have a
huge influence on the quality of life. The incidence of fatigue in patients using Sunitinib
in phase I studies was 70% and the fatigue was often dose limiting. (1-4) In phase II-III
studies the incidence was 27% - 51%. 5,6 In a phase III randomized, double-blind
placebo-controlled trial of Sorafenib the incidence of fatigue in the Sorafenib group was
37% and in the placebo group 28%. (7) It is possible that fatigue is a symptom of depression
or anxiety, alternatively, prolonged fatigue in itself can lead to depression or anxiety.8
There has been found a significant and positive correlation between anxiety and depressive
symptoms and fatigue after treatment for cancer.