**10. Conclusion**

**8.4. Other biomarkers**

174 Renal Tumor

biomarkers. [113-115]

**9.1. Therapy**

Emerging data has also shown that other adverse effects such as hypothyroidism, myelosup‐ pression in addition to the aforementioned hypertension and hand foot syndrome were biomarkers for tumour control and OS when sunitinib is the agent in use. [111, 112] In mTOR inhibitors, serum LDH, elevated cholesterol and pneumonitis have been studied as predictive

**9. Quality of life in patients with renal cell carcinoma receiving targeted**

Quality of life (QoL) has been evaluated in a series of trials of patients taking novel targeted agents for RCC. Questionnaires used have included the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT Kidney Symptom Index-15 item (FKSI-15), the FACT-Kidney Symptom Index-Disease related Symptoms (FKSI-DRS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and

One of the important outcomes was that newer treatment approaches may be better tolerated with improved QOL compared to the older generation agents. Sunitinib has shown meaningful differences, both in kidney cancer related symptoms and overall QOL over IFN-α. [33] This is

Sorafenib, on the contrary revealed no worst QoL score based on the FACT-G or FKSI-15 undertaken in the TARGET trial. On the other hand, targeted therapies compared to placebo were not revealing worse scores in the QOL questioners. Interestingly, qualitative assessment of one's ability to enjoy life, concerns for well-being, fevers, dyspnea and cough were reported

Pazopanib unexpectedly did not have a clinically different QoL compared with placebo,

In the AXIS trial where axitinib was compared head-to-head with sorafenib, patient-reported kidney-specific symptom and function assessments were secondary endpoints that were examined. [57] Overall, patients on the axitinib treatment arm reported comparable outcomes to that of sorafenib. The PFS benefit seen by axitinib is associated with a delay in worsening of the composite endpoint of advanced RCC symptoms, progression, or death with sorafenib. [57] PSICES is a small but important randomized trial comparing patient's preference for pazopa‐ nib or sunitinib for first-line treatment of metastatic RCC. The rationale of this trial was to select the more tolerable agent with the recent approval of numerous TKIs as front-line agents. [117] One hundred and sixty nine patients with metastatic RCC were randomly assigned to blinded treatment of pazopanib for 10 weeks with a wash out prior to 50mg of sunitinib for 10 weeks, and vice versa (4 weeks of sunitinib followed by 2 weeks break before 10 weeks of pazopanib). Fifty four and sixty patients first received pazopanib and sunitinib respectively. The patience

despite the adverse events that a clinician may expect with pazopanib. [50, 100]

the Euro QOL 5D (Index and Visual Analogue Scale) utility score (EQ-5D) Index.

not unexpected given the more difficult toxicity profile of sunitinib.

less in the patients on sorafenib. [116]

The discovery of anti-angiogenic (small molecule tyrosine kinase inhibitors and anti-VEGF agents) agents has altered the treatment landscape for patients with metastatic RCC. Their effective anti-neoplastic activities have provided hope of survival beyond six month, in contrast to that traditionally gained from IFN-α therapy. Different treatment strategies are being investigated vigorously, either in combination or in sequence with the aim of improving the pre-existing survival and response rates. Whilst the treatment algorithm for advanced clear-cell variant of renal cell carcinoma is constantly evolving with increasing treatment options, the non clear-cell counterpart remains an area in need of significant research. With improved understanding of the various molecular pathways, options for non clear-cell variants would hopefully become more established. The recognition of the potentially serious side-effects of targeted agents begs for vigilance in the clinician's part to improve treatment adherence and compliance. Close monitoring of these toxicities will also allow for better identification of their role as bio-markers of efficacy. The ultimate goal is to have an effective agent that leads to durable response with a tolerable side-effect profile.

### **Acknowledgements**

We wish to express our gratitude to Ms. Judith Lees, Senior Cancer Pharmacist, RAH Cancer Centre, for assistance with new drugs information.

## **Author details**

Thean Hsiang Tan, Sina Vatandoust and Michail Charakidis

RAH Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia
