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Patient-Focused Approach

Chapter 19 - Renal Cell Cancer

The populations enrolled in the pivotal RCTs differ, which renders comparisons regarding efficacy and tolerability difficult. Patients with mRCC represent a heterogeneous group and no single agent will provide optimal benefit to all patients. In addition, populations recruited to RCTs under-represent certain patient subtypes, notably the elderly and those with comorbidities. Consequently, the suitability of a specific targeted agent for a given patient group, such as the elderly, will depend on a number of factors, including disease-, patient- and treatment-related characteristics. Data from expanded access studies and clinical experience may be as relevant as the results of RCTs when making the difficult decision regarding which agent is best for a specific patient.

A schema has been proposed to show how different sources of data can be integrated when selecting treatments. This takes into account nine factors relevant to clinical decision making and provides an easily understandable visual indication when assigning the strength with which a particular agent can be recommended for use in specific patient subgroups (Fig. below). In this “patient-focused schema,” an individualised approach to treatment selection is proposed. Treatment should be tailored according to the available agent (sunitinib, axitinib, pazopanib, sorafenib, bevacizumab, temsirolimus, or everolimus) to meet individual circumstances and needs. For a given case, patient-, disease-, and treatment-related characteristics should be evaluated individually. These should be taken into consideration together with the efficacy and toxicity/tolerability profile of each targeted agent to allow a tailored treatment.

Parameters to consider when choosing an appropriate treatment for the individual patient with renal cell cancer

We recommend the integration of this approach into everyday clinical practice, even though achieving this is a considerable clinical challenge. Notably, recently published international guidelines for the treatment of RCC, such as the kidney cancer guidelines from the National Comprehensive Cancer Network (NCCN), recognise the importance of an individualised approach to therapy and base their recommendations on broader criteria, emphasising the value of clinical judgement and experience to support treatment decisions for individual patients.

In the absence of controlled comparisons between the agents discussed in an elderly population, it is not possible to say that any one of these agents is more or less suited for use in elderly patients.

Even an indirect comparison of the relative frequency or severity of a specific toxicity is inappropriate since the phase III studies, which provide the most robust toxicity data, were conducted in different populations and the side effects of treatment were assessed by different groups of investigators.

Most Common Adverse Events (All Grades) in Descending Order of Frequency, as Reported in the Pivotal Studies with Single-Agent Targeted Therapy.

AgentNon-haematological adverse eventHaematological adverse eventsOther laboratory abnormalities
AxitinibHypertension
Fatigue
Decreased appetite
Nausea
Dysphonia
Hand-foot skin reaction
Hypothyroidism
Weight loss
None listedNone listed
PazopanibFatigue
Changes in hair colour
Hand-Foot skin reaction
Dysgeusia
Rash
Constipation
Weight loss
Alopaecia
Leukopaenia
Thrombocytopaenia
Increased AST
Increased ALT
SorafenibDiarrhoea
Rash or desquamation
Fatigue
Hand-foot skin reaction
Alopaecia
Nausea
Pruritis
Hypertension
Anorexia
Vomiting
Decreased haemoglobinNone listed
SunitinibDiarrhoea
Fatigue
Nausea
Stomatitis
Vomiting
Hypertension
Hand-foot syndrome
Mucosal inflammation
Rash
Asthenia
Leukopaenia
Neutropaenia
Increased creatinine
Increased lipase
TemsirolimusAsthenia
Rash
Nausea
Anorexia
Pain
Dyspnoea
Infection
Diarrhoea
Peripheral oedema
Cough
Anaemia
Thrombocytopaenia
Hyperlipidaemia
Hyperglycaemia

Reprinted from Bellmunt J, Négrier S, Escudier B, et al. Crit Rev Oncol Hematol 2009; 69:64–72, with permission from Elsevier. AST, aspartate transaminase; ALT, alanine transaminase.

However, considering the ranking of toxicities as they appeared for each agent in the pivotal phase III studies (Table above) might be reasonable for a personalised approach when assessing treatment options in an individual patient with comorbidities, especially when taken together with the “patient-focused schema.” A definitive answer to the question of whether drugs should be selected according to specific comorbidities will require prospectively designed trials.

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