Toxicities of targeted therapy and their management in kidney cancer

Context: The therapeutic scenario for metastatic renal cell carcinoma (mRCC) has been evolving rapidly, with sunitinib, sorafenib, bevacizumab, everolimus, pazopanib, and temsirolimus being successfully tested and approved in a short period of time. Oncologists must be familiar with the management of toxicity that these biologic agents cause, as such toxicity is different from that of conventional chemotherapeutic agents.

Objective: To describe toxic effects associated with targeted therapy of mRCC and their proper management on the basis of currently available evidence.

Evidence acquisition: We conducted a systematic analysis of the literature on 15th October 2010 by performing a search of Medical Subject Headings (MeSH) on PubMed using the words sorafenib, sunitinib, bevacizumab, everolimus, pazopanib, or temsirolimus combined with the MeSH term kidney neoplasms. Consideration for inclusion was given to articles providing data concerning (1) incidence and grading and (2) management of targeted therapy-related toxic effects. A separate search was conducted on PubMed to retrieve meta-analyses using each drug name and the word meta-analysis.

Evidence synthesis: Hypertension, fatigue, bone marrow toxicity, skin toxicity, and gastrointestinal side-effects are common with the six targeted agents. Everolimus and temsirolimus are associated with immunosuppression, metabolic alterations, and interstitial pneumonitis, while sunitinib is associated with hypothyroidism. Recommendations for treating these conditions usually follow those for the general population because of the lack of experimental data in this setting (eg, for management of sunitinib-induced hypertension).

Conclusions: The treating oncologist should try to manage side-effects associated with targeted therapy using supportive and pharmacologic interventions. Severe toxicity requires external specialist consultation and treatment suspension and/or dose reduction. Experimental data about the management of targeted therapy-related toxicity in mRCC is lacking and required in this setting.