The prospects for combination therapy with capecitabine in the rapidly evolving treatment landscape of renal cell carcinoma

ABSTRACT

Introduction: Although significant advances have been made in the treatment of advanced renal cell carcinoma (RCC), patients still develop resistance to standard therapies and require the administration of subsequent lines of treatment. New therapeutic approaches are thus imperative to improve the prognosis for patients with RCC.

Areas covered: Based on the current literature, we summarize the treatment of metastatic RCC, including the use of cytotoxic chemotherapy, in this review article. We also review the existing scientific literature regarding the role of capecitabine in the treatment of RCC.

Expert opinion: Currently, targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors are widely used in the treatment of metastatic RCC. More recently, the role of immune checkpoint inhibitors has been established in the treatment of advanced RCC. Traditionally, the use of cytotoxic chemotherapy in the treatment of RCC is limited. However, cytotoxic chemotherapy may have benefit in different types of RCC, such as variant histology. Furthermore, new combinations of chemotherapy with immune checkpoint inhibitors may provide new treatment options for our patients.

KEYWORDS:

• Capecitabine
• renal cell carcinoma
• targeted treatment
• immunotherapy
• chemotherapy
• biomarkers

Article highlights

• Despite major advances with targeted therapy and immunotherapy in advanced RCC, many patients do not respond or progress and need salvage treatment.

• Capecitabine is an orally administered chemotherapeutic, enzymatically converted to 5-fluorouracil (5-FU) in the body, which is generally well tolerated but minimally effective as a single agent in RCC.

• Capecitabine and gemcitabine combinations showed encouraging ORR and survival rates in advanced RCC across multiple phase II trials of differing histologic subtypes, but have not been confirmed in a randomized phase III trial.

• Combinations of capecitabine with VEGF and multi-targeted TKIs were complicated by high rates of toxicity precluding standard use.

• Immunotherapy plus capecitabine holds promise based on combination studies with IFN alpha and the advent of checkpoint inhibitors that have favorable toxicity profiles. Future research will focus on novel combinations of cytotoxic and/or targeted agents that enhance the activity of immunotherapies.

This box summarizes key points contained in the article.

Declaration of interest

M. A. Bilen has served as a consultant for Exelixis, Sanofi. G. Sonpavde has received grants to his institution from Boehringer-Ingelheim, Bayer, Onyx-Amgen, Merck; served as a consultant for Pfizer, Genentech, Novartis, Argos, Merck, Sanofi, Agensys, Clinical Care Options, Astrazeneca, Uptodate, Biotheranostics, Exelixis, Bristol-Myers-Squibb, Janssen, Amgen, Eisai, and personal fees from NCCN (National Comprehensive Cancer Network). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.