Prospective Clinical Trial of Preoperative Sunitinib in Patients With Renal Cell Carcinoma

Abstract

Introduction Sunitinib is an approved treatment for metastatic renal cell carcinoma (RCC). A prospective clinical trial was conducted to evaluate the safety and clinical response to sunitinib administered prior to nephrectomy in patients with localized or metastatic clear cell RCC. Methods Patients with biopsy-proven clear cell RCC were enrolled and treated with sunitinib malate, 37.5 mg daily, for 3 months prior to nephrectomy. The primary endpoints was safety. Results Twenty patients were enrolled during an 18 month period. The most common toxicities were GI symptoms and hematologic. Grade 3 toxicities occurred in 6 patients (30%). No surgical complications were attributable to treatment with sunitinib. Seventeen of the 20 patients (85%) experienced a decrease in tumor diameter (mean change −11.8%, range −27% to 11%) and cross-sectional area (mean change −27.9%, range −43% to 23%). Enhancement on contrast-enhanced CT decreased in 15 patients, with a mean change in Hounsfield units of −22% (range −74% to 29%). Following a decrease in tumor size, 8 patients with cT1b tumors underwent laparoscopic partial nephrectomy. Surgical parameters such as blood loss, transfusion rate, operative time, and complications were similar to those who underwent surgery during the study period and were not enrolled on the trial. Conclusions Preoperative treatment with sunitinib is safe. Sunitinib decreased the size of primary RCC in 17 of 20 patients, and future trials can be considered to evaluate the use of neoadjuvant sunitinib to maximize nephron-sparing and decrease recurrence risk for high-risk, localized RCC.

The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

“…Although many of the prior studies rely on the RECIST to standardize treatment response, it is important to note that RECIST and WHO criteria have been broadly found to overlook minor but representative tumor responses commonly encountered with systemic therapy, as targeted therapy may increase intratumoral necrosis without significant tumor diameter reduction [Hellenthal et al 2010]. Furthermore, other studies have demonstrated that the loss of radiographic enhancement and intratumoral density may represent more important alternatives to estimate the effect of preoperative therapy in tumor perfusion rather than reduction in tumor size [Cowey et al 2010b].…”

“…After sunitinib treatment, Hellenthal and colleagues were able to perform laparoscopic partial nephrectomy in eight of the 20 patients included in their prospective study [Hellenthal et al 2010]. Six patients developed grade 3 toxicity from targeted therapy, but no surgical complications were attributable to sunitinib use.…”

The use of preoperative targeted molecular therapy to allow nephron sparing for T1b tumors

“…Although much of the data on TMT and volumetric reduction concerns masses prior to radical nephrectomy, some data exist on use of TMT prior to NSS (Table 1) [17,[21][22][23][24][25][26]. In terms of volumetric reduction, Kroon et al [27 && ] conducted an analysis of 89 tumors treated with preoperative TKIs and found that smaller initial size was associated with a greater volumetric reduction.…”

“…Initial case reports suggested that TMTs are potentially effective and well tolerated to use as preoperative therapy for clear cell RCC (ccRCC) before NSS [21][22][23][24][25][26]. Ansari et al [26] presented the case of a woman with two unresectable lesions in her solitary right kidney 15 months after left radical nephrectomy for T3N0M0 ccRCC.…”

“…Hellenthal et al [22] reported a larger series of preoperative TMT before NSS in a prospective, openlabel study. Twenty patients had localized (n ¼ 16) or metastatic ccRCC (n ¼ 4) and received 90 days of sunitinib.…”