180

Practical Urology: EssEntial PrinciPlEs and PracticE

Immunotherapy

(sunitinib and sorafenib), mammalian target

of rapamycin inhibitors (temsirolimus), and

Until recently, treatment of mRCC has been

monoclonal antibodies (bevacizumab) appear

based on nephrectomy and limited use of toxic

to be the most promising agents for treatment

and often ineffective immunotherapy with

of mRCC. Table 13.3 presents a summary of

interferon-alpha (IFN-a) and interleukin-2 (IL-

phase III randomized controlled trials of

2). Both are beneficial only for mRCC patients

targeted therapies in renal cell carcinoma.

with a good performance status and clear cell

Sunitinib, sorafenib, temsirolimus, and the

subtype histology. IFN-a (alpha) can be used as

combination bevacizumab with interferon-

comparative control arm for studies investigat-

alpha are approved for treatment of mRCC.33-37

ing the efficacy of new drugs for mRCC patients.

Sunitinib is advised as first-line therapy in

High-dose IL-2 may induce durable complete

low-and intermediate-risk mRCC patients.

responses in a minority of patients ranging

Bevacizumab and interferon-alpha can be con-

from 7% to 27%; however, it has more side

sidered as an additional option for first-line

effects than IFN-a (alpha). Combination of

therapy in these patients. Temsirolimus should

cytokines, with or without additional chemo-

be considered as first-line treatment in poor-

therapy, does not improve OS compared with

risk mRCC patients. Sorafenib has proven effi-

monotherapy.30

cacy as second-line therapy for mRCC after

failure of cytokine therapy. These new agents

Angiogenesis Inhibitor Drugs

improve quality of life and seem able to stabi-

lize mRCC for a prolonged period of time.30

Major advances in the understanding of the

The mTOR inhibitor everolimus also shows

promising results in patients with mRCC.38

molecular biology of RCC have led to the

Studies are ongoing to compare combination

development of several new therapies that tar-

therapies with single agents and to determine

get ligands at the molecular level, so-called

the efficacy of single agents as adjuvant ther-

“targeted therapies”. Figure 13.1 presents the

apy after nephrectomy.

major targets for these targeted therapies.

Small molecule tyrosine kinase inhibitors