Neoadjuvant therapy of renal cell carcinoma: a novel treatment option in the era of targeted therapy?

The study was carried out to evaluate the effectiveness, toxicity and optimal duration of neoadjuvant therapy for patients with organ-confined or locally advanced renal cell carcinoma in the era of targeted agents. A literature review was carried out using Medline/Pubmed articles, as well as congress reports from the last five American Society of Clinical Oncology, American Urological Association and European Association of Urology Annual Meetings. Neoadjuvant targeted therapy is feasible and shows toxicity similar to that seen in a palliative setting. Most studies recommend an application for 2-4 months. The current data situation is best for sunitinib. Surgery can apparently be carried out the day right after discontinuing the drug. However, even sunitinib leads to only a mean 10% decrease in primary tumor size, and one-quarter to one-fifth of all patients show local tumor progression during treatment. Few patients (approximately 12%) with a vena cava tumor thrombus achieve a significant decrease in its level under neoadjuvant therapy; here too, progression is observed in a significant number of cases. Even the new targeted agents show limited effectiveness in achieving relevant remissions of the primary tumor. Furthermore, tumor progression is seen in a significant percentage of patients during neoadjuvant therapy. Thus, even today in the era of targeted agents, a neoadjuvant approach should only be made in patients with localized or locally advanced renal cell carcinoma, which primarily seem to be absolutely inaccessible by (partial) nephrectomy.

Present state of target therapy for disseminated renal cell carcinoma.

Both experimental and clinical researches focusing on advanced kidney cancer have increased continuously since the successful introduction of targeted therapy in the treatment of advanced metastatic renal cell carcinoma. Being refractory to conventional hormone therapy, chemotherapy or radiotherapy, renal cell carcinoma has become a model tumor for the development and evaluation of diverse novel targeted drugs. This review highlights currently available agents and summarizes evidence-based data regarding their effectiveness in metastatic renal cell carcinoma. Furthermore, the role of debulking tumor nephrectomy followed by systemic therapy as part of an optimum treatment algorithm is being elucidated.

Application of retinoids in the treatment of renal cell carcinoma--a futile effort?

The therapeutic benefit of adding retinoids such as all-trans retinoic acid (RA), 9-cis-RA or 13-cis-RA to established single-agent or combination immuno/chemotherapy regimens for the treatment of metastatic renal cell carcinoma (RCC) has been extensively investigated during the last decade. However, at present results are contradictory and their application controversial. Moreover, recent studies indicated a significantly higher incidence of toxic side-effects in patients treated with retinoids in addition to established bio/chemotherapy. This Commentary summarizes preclinical and clinical trials investigating efficacy and toxicity of retinoids in the treatment of RCC.