Bex A, Van der Veldt AA, Blank C, Van den Eertwegh AJ, Boven E, Horenblas S, Haanen JNeoadjuvant sunitinib for surgically complex advanced renal cell cancer of doubtful resectability: initial experience with downsizing to reconsider cytoreductive surgery. World J Urol 27: 533-539
To evaluate neoadjuvant sunitinib in patients with synchronous metastatic renal cell cancer (mRCC) to downsize surgically complex tumours and reconsider cytoreductive surgery.
Retrospective analysis of ten consecutive mRCC patients treated with sunitinib in an expanded access program who presented with surgically complex primary tumours or bulky locoregional metastases. Surgery-limiting tumour sites (SLTSs) were defined as primary or retroperitoneal lesions with direct invasion of adjacent organs or encasement of vital structures on imaging. Patients received sunitinib 50 mg/day for 4 weeks on and 2 weeks off to be followed by cytoreductive surgery after downsizing and individual reassessment. Response was measured according to Response Evaluation Criteria in Solid Tumours (RECIST).
Six out of ten SLTSs revealed a reduction of tumour size with a median of 14% according to RECIST. None of the ten SLTSs had a partial response (PR), whilst at distant metastatic sites one complete remission and two PRs occurred. Downsizing of SLTSs appeared most prominent in the first 2-4 months, which resulted in reconsidering cytoreductive nephrectomy in three patients. These three tumours invaded the liver on imaging and were reduced by 11, 18 and 20%.
In this patient group with mRCC and surgically complex primary tumours or locoregional metastases, downsizing of SLTSs by neoadjuvant sunitinib was limited. Cytoreductive surgery was reconsidered in three patients. Given the overall reduction in tumour burden by sunitinib alone, further investigation to define the role of cytoreductive surgery is warranted.
"Some observed difficulties due to fibrosis whereas others experienced dissection facilitated by edema in the tissue planes . Neoadjuvant therapy results in a delay of curative surgery by at least 2 to 3 months as most of the downsizing occurs in the first months  . This may be potentially harmful as tumor progression may occur. "
[Show abstract][Hide abstract] ABSTRACT: With an increasing number of small renal masses being diagnosed organ-preserving treatment strategies such as nephron-sparing surgery (NSS) or radiofrequency and cryoablation are gaining importance. There is evidence that preserving renal function reduces the risk of death of any cause, cardiovascular events, and hospitalization. Some patients have unfavourable tumor locations or large tumors unsuitable for NSS or ablation which is a clinical problem especially in those with imperative indications to preserve renal function. These patients may benefit from downsizing primary tumors by targeted therapy. This paper provides an overview of the current evidence, safety, controversies, and ongoing trials.
International Journal of Surgical Oncology 06/2012; 2012:250479. DOI:10.1155/2012/250479
"The majority have only limited downsizing, but there are exceptional responses with a small proportion of cases experiencing >30% reduction in the diameter of observed lesions  . The ability to predict this reliably would be of significant benefit because patients with potentially unresectable disease might have substantial downsizing of their caval or nodal tumour masses, making them possible candidates for curative or debulking surgery, with an associated reduction in the concomitant morbidity of surgical intervention . Unfortunately, retrospective analyses of poorly categorised patient subgroups in relatively small series such as the one currently reported will not facilitate the identification of these individuals. "
"Primary tumours were also excluded, as the overall response may be underestimated due to their enormous size (Van der Veldt et al, 2008b; Bex et al, 2009). Furthermore, brain (Helgason et al, 2008) and bone metastases at baseline were excluded. "
[Show abstract][Hide abstract] ABSTRACT: Because sunitinib can induce extensive necrosis in metastatic renal cell cancer (mRCC), we examined whether criteria defined by Choi might be valuable to predict early sunitinib efficacy.
Computed tomography was used for measurement of tumour lesions in mm and lesion attenuation in Hounsfield units (HUs). According to Choi criteria partial response (PR) was defined as > or =10% decrease in size or > or =15% decrease in attenuation.
A total of 55 mRCC patients treated with sunitinib were included. At first evaluation, according to the Response Evaluation Criteria in Solid Tumours (RECIST) 7 patients had PR, 38 stable disease (SD), and 10 progressive disease (PD), whereas according to Choi criteria 36 patients had PR, 6 SD and 13 PD. Median tumour attenuation decreased from 66 to 47 HUs (P< or =0.001). In patients with PR, Choi criteria had a significantly better predictive value for progression-free survival and overall survival (both Ps<0.001) than RECIST (P=0.685 and 0.191 respectively). The predictive value for RECIST increased (P=0.001 and <0.001 respectively), when best response during treatment was taken into account.
Choi criteria could be helpful to define early mRCC patients who benefit from sunitinib, but the use of these criteria will not change the management of these patients.
British Journal of Cancer 02/2010; 102(5):803-9. DOI:10.1038/sj.bjc.6605567 · 4.84 Impact Factor
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