Update on systemic therapies of metastatic renal cell carcinoma.
OBJECTIVE
Recent advances in understanding the molecular biology of advanced and metastatic renal cell carcinoma (RCC) have led to the development of several targeted agents that show impressive antitumor efficacy. The integration of these drugs into clinical practice has revolutionized the therapeutic management of RCC.


METHODS
We reviewed data on all approved targeted agents in the first-line and second-line setting, as well as, studies involving sequential therapy. Data from phase III trials are discussed, and an optional therapeutic algorithm is presented.


RESULTS
Sunitinib should be used as the first-line treatment of choice for good- and intermediate-risk patients according to Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, whereas temsirolimus is recommended for the poor-risk group. The combination of bevacizumab and INF-alpha can be regarded as an alternative to sunitinib. After cytokine failure, patients should be recommended to sorafenib. Everolimus must be considered after first-line failure of a tyrosine kinase inhibitor (TKI); furthermore, recent evidence suggests sequential use of TKIs before administration of everolimus.


CONCLUSIONS
A range of potent drugs are available to patients with metastatic RCC. Treatment decisions should be made carefully taking into consideration that all targeted agents only have a palliative effect with prolongation of life, but do not cure metastatic RCC.
Herrmann
E
E
Department of Urology, University of Münster, Albert-Schweitzer Strasse 33, 48149, Münster, Germany. herrmae@ukmuenster.de
Bierer
S
S
Wülfing
C
C
D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects; D000068258:Bevacizumab; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077157:Sorafenib; D000077210:Sunitinib; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000068258:Bevacizumab; D000068338:Everolimus; D000077157:Sorafenib; D000077210:Sunitinib; D020123:Sirolimus