A review of the current role of targeted therapy in the treatment of metastatic renal carcinoma, "Beyond the Abstract," by Paulo Jaworski, MD

BERKELEY, CA (UroToday.com) - In our recent article, we have reviewed the current role of targeted therapy for metastatic renal cell carcinoma (mRCC) with detailed information on pharmacokynetics and outcomes. The use of these drugs has been well established as adjuvant treatment of mRCC.

Interleukin 2 and interferon alfa had been the main strains of advanced RCC pharmacologic treatment, and surgery was an option for those where curative intent was possible. Cytoreductive nephrectomy showed an increased life expectancy by 6 months. With the emergence of targetws therapy for RCC, neoadjuvant treatment became a feasible option for patients with poor renal function and locally advanced disease.

Neoadjuvant targeted therapy remains a subject of trials that strive to prove its efficacy. When surgery is not an option, this therapy is implemented to reduce metastasis and tumor burden prior to cytoreductive nephrectomy. Patients treated with targeted therapy medication also may avoid undergoing radical nephrectomy. Partial nephrectomy proved beneficial for some patients with metastatic disease, especially in those with methacronous contralateral lesions.[1] Less invasive surgical options such as laparoscopic cryoablation of renal tumors are used with comparable outcomes to conventional partial nephrectomy,[2] but there is no data regarding this surgical approach in the cytoreductive treatment for RCC.

The use of neoadjuvant targeted therapy may be appealing, but undesirable side effects can be harmful and contra-indicated for neoadjuvant treatment. A few examples are impaired wound healing, increased bleeding, and cardiovascular complications.[3] Therefore, many trials have been designed to test the safety of targeted therapy in the neoadjuvant setting.

As of December 2013, there were 5 ongoing trials and 3 published studies on neoadjuvant targeted therapy. The published studies were conducted with sorafenib and sunitinib. Conclusions varied according to the endpoint (feasibility, adverse effects, safety). However, all drugs demonstrated promising results in the decrease of tumor size and the increase in surgical safety.[4]

Hellenthal et al. studied the safety of surgery after 90 days of sunitinib treatment as well as safety in patients with a primary kidney tumor. Patients ranged from clinical T1b to T3, regardless of N and M categories.[5] Contrast-enhanced CTs of the abdomen and pelvis were used to determine tumor size prior to surgery. The results were compared to his historic control group. This study concluded that there was a decrease in primary tumor size in 85% of the patients being treated. There were no intraoperative and postoperative surgical complications that derived from the use of neoadjuvant sunitinib.

Cowey et al. conducted a pilot trial that evaluated surgical safety and feasibility with neoadjuvant sorafenib in patients who either had a high risk for recurrence or were undergoing cytoreductive nephrectomy.[6] Patients with clinical stage II RCC were included. Sorafenib was administered for 4 weeks prior to the surgery, and imaging was acquired (contrast-enhanced CT scans of the abdomen and pelvis). Tumor size decreased notably, and surgery did not appear to have more complications despite possible side effects from the drug.

Hellenthal and Cowey also found that a majority of the patients experienced a decrease in both tumor size and density of tumor cells. The reduction in size and tumor burden was shown by less contrast enhancement in CT scans.

Other trials testing the safety of temsirolimus, axitinib, pazopanib and everolimus are still under development.

Much is yet to be known about long-term clinical results and benefits, such as improvement in quality of life, chance of recurrence, and better morbidity and mortality rates. Larger, multi-centric trials with longer follow-up times assessing clinical outcomes objectively are still necessary in order to determine the observed benefit of neoadjuvant targeted therapy. While neoadjuvant targeted therapy has been shown to play a beneficial role in the multimodal treatment therapy for metastatic renal cell carcinoma, the prices of these drugs remain high.

References:

  1. Babaian, K.N., et al., Partial nephrectomy in the setting of metastatic renal cell carcinoma. J Urol, 2014.
  2. Tanagho, Y.S., et al., Renal Cryoablation versus Robot-Assisted Partial Nephrectomy: Washington University Long-Term Experience. J Endourol, 2013.
  3. Jonasch, E., et al., Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma. J Clin Oncol, 2009. 27(25): p. 4076-81.
  4. Ho, D. and H.L. Kim, The Potential Role for Neoadjuvant Therapy in Renal Cell Carcinoma. Clin Adv Hematol Oncol. 2013 Dec;11(12):777-82.
  5. Hellenthal, N.J., et al., Prospective clinical trial of preoperative sunitinib in patients with renal cell carcinoma. J Urol, 2010. 184(3): p. 859-64.
  6. Cowey, C.L., et al., Neoadjuvant clinical trial with sorafenib for patients with stage II or higher renal cell carcinoma. J Clin Oncol, 2010. 28(9): p. 1502-7. 

Written by:
Paulo Jaworski, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Denver Health Medical Center, Denver, CO USA

Targeted therapy in metastatic renal carcinoma - Abstract

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