The safety and efficacy of sunitinib before planned nephrectomy in metastatic clear cell renal cancer

Abstract

Background: The safety and efficacy of upfront sunitinib, before nephrectomy in metastatic clear cell renal cancer (mCRC), has not been prospectively evaluated.Methods: Two prospective single-arm phase II studies investigated either two cycles (study A: n = 19) or three cycles (study B: n = 33) of sunitinib before nephrectomy in mCRC.Results: Overall, 38 of 52 (73%) of patients obtained clinical benefit (by RECIST) before surgery. The partial response rate of the primary tumour was 6% [median reduction in longest diameter of 12% (range 8%−35%)]. No patients became ineligible due to local progression of disease. A nephrectomy was carried out in 37 (71%) of patients. Necrosis (>50%) was a prominent feature at nephrectomy in 49%. Surgical complications (Clavien–Dindo classification) occurred in 10 (27%) patients, including one death (3%). The median blood loss and surgical time were 725 (90–4200) ml and 189 (70–420) min, respectively. The median progression-free survival was 8 months (95% confidence interval 6–15 months). A comparison of two versus three pre-surgery cycles showed no significant difference in terms of surgical complications or efficacy.Conclusions: Nephrectomy after upfront sunitinib can be carried out safely. It obtains control of disease. Randomised studies are required to address if this approach is beneficial.

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

“…However, there were areas of concern. Delays in wound healing, thought to be related to VEGF targeted therapy, were reported in this and other smaller series 7 . Also, 39% of patients did not have nephrectomy.…”

“…Comparisons with pazopanib and sunitinib are not possible in this setting, largely due to the small size of the studies and variability in protocol design 7 . Both drugs have clinical benefit rates above 70% in this setting although the sunitinib trials focused mainly on safety rather than efficacy.…”

“…Also, significant time off systemic therapy is required during the peri-operative period which may allow for the development of resistance to therapy. Finally it has been reported in previous small safety studies that although this upfront approach is feasible, surgery may be more complex due to additional treatment related necrosis and delayed wound healing 7,8 .…”

“…This has theoretical advantages in that systemic therapy can commence more rapidly, and there may be significant shrinkage of the primary tumor facilitating surgery. It is also possible that this upfront approach selects out patients with rapidly progressive VEGF resistant disease who have a very short life expectancy and may not benefit from nephrectomy 5,7 . There are also potential risks to this approach.…”

Neoadjuvant targeted therapy in patients with renal cell carcinoma

“…В ито-ге 37 (70 %) пациентам из 52 выполнили нефрэктомию Таблица 1. Неоадъювантная таргетная терапия у больных ПКР [20][21][22][23][24][35][36][37][38][39][40][41][42][43] …”