Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma.

Cabozantinib is an oral tyrosine-kinase inhibitor whose targets include VEGFR, MET, and AXL. Cabozantinib is approved for the treatment of patients with advanced clear-cell renal-cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the pivotal Phase III trial of second-line RCC, cabozantinib was associated with a significant improvement in overall survival, progression-free survival, and antitumor response compared with everolimus.

Optimizing patient adherence to targeted therapies in renal cell carcinoma.

The current standard of care for treating metastatic renal cell carcinoma is sequential therapy with vascular endothelial growth factor-targeted agents (i.e., axitinib, bevacizumab, pazopanib, sorafenib, and sunitinib) and mammalian target of rapamycin inhibitors (i.

A phase Ib study of combined VEGFR and mTOR inhibition with vatalanib and everolimus in patients with advanced renal cell carcinoma.

Background: Vatalanib is an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), whereas everolimus inhibits mammalian target of rapamycin (mTOR). Combination therapy with VEGFR and mTOR inhibitors has not been well tolerated to date but may have efficacy in renal cell carcinoma (RCC).

Patients And Methods: A phase Ib study of vatalanib and everolimus was performed in patients with advanced solid tumors to determine the maximum tolerated dose (MTD), safety, and tolerability of the combination.

A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer.

Purpose: Given discrepancies between preclinical and clinical observations of mammalian target of rapamycin (mTOR) inhibition in prostate cancer, we sought to determine the pharmacodynamic effects of the mTOR/TORC1 inhibitor rapamycin in men with intermediate- to high-risk prostate cancer undergoing radical prostatectomy.

Experimental Design: Rapamycin was given at 3 or 6 mg orally for 14 days before radical prostatectomy in men with multifocal Gleason sum > or =7 prostate cancer; 10 untreated control subjects were included. The primary outcome was inhibition of phosphorylation of ribosomal S6 in posttreatment radical prostatectomy versus pretreatment biopsy tumor tissue, evaluated using a Simon two-stage design for pharmacodynamic efficacy.

Management of mTOR inhibitor side effects.

Although surgery remains the primary curative treatment for renal cell carcinoma (RCC), systemic therapy also is indicated in the advanced disease setting. This article reviews the role of mammalian target of rapamycin inhibitors in the treatment of metastatic RCC. A case study is presented to illustrate side-effect management issues commonly encountered by oncology nurses in clinical practice.