Article

Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery

Division of Urology, Department of Surgery, University of California San Diego, School of Medicine San Diego, CA, USA.
BJU International (Impact Factor: 3.13). 11/2010; 106(9):1270-6. DOI: 10.1111/j.1464-410X.2010.09357.x
Source: PubMed

ABSTRACT To investigate efficacy of neoadjuvant tyrosine kinase-inhibitor therapy (TKI) before imperative nephron-sparing surgery (NSS), as NSS in patients with large locally advanced or centrally located tumours can be challenging, and TKI therapy might result in a reduction of primary tumour burden and increase the feasibility of NSS.
This was a multicentre retrospective review and prospective pilot study of patients undergoing neoadjuvant sunitinib before planned NSS from February 2006 to February 2009. All patients underwent confirmatory biopsy for clear cell renal cell carcinoma. Patients received two 28-day cycles of sunitinib before NSS. Demographics/tumour characteristics, tumour response (by the Response Evaluation Criteria In Solid Tumors), outcomes and complications were analysed.
Twelve patients (seven men and five women; mean age 60.1 years, tumours on 14 renal units) were given TKI before NSS for imperative indications. The mean pretreatment tumour diameter was 7.1 cm; all patients had a decrease in size of the primary tumour after TKI, with a mean reduction in maximum diameter of 1.5 cm (21.1%). Four of 14 and 10 of 14 primary tumours had a partial response and stable disease after TKI. NSS was achievable in all 14 kidneys. Four patients had a concurrent metastasectomy. The mean warm ischaemia time was 22.5 min; postoperative dialysis was not required in any patients. Final pathology revealed negative tumour margins in all 14 tumours. The mean creatinine and estimated glomerular filtration rate (before/after NSS) were 1.34/1.40 mg/dL (P = 0.431) and 57.7/53.4 mL/min/1.73 m(2) (P = 0.475), respectively. At a mean follow-up of 23.9 months, 10 of the 12 patients were alive, one died from metastatic RCC and none required dialysis. Three of the 14 renal units developed delayed urinary leaks, all in patients who also received postoperative sunitinib. All leaks resolved with conservative measures.
Neoadjuvant TKI followed by NSS is safe and feasible, with all patients achieving a reduction in maximum tumour diameter, and with NSS being achievable with negative margins and with no requirement for postoperative dialysis. Further investigation is required.

1 Follower
 · 
112 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Metastatic renal cell carcinoma (mRCC) is a challenging disease. Despite the new targeted therapies, complete remissions occur only in 1%-3% of the cases, and the most effective first-line treatment drugs have reached a ceiling in overall survival (ranging from 9 to 49 mo). Metastasectomy remains to be the only curative option in most patients with mRCC. Prognostic nomograms have been recently published, so we have tools to classify patients in risk groups, allowing us to detect the cases with the higher risk of recurrence after metastasectomy. Although sparse, there is some evidence of effectiveness of neoadjuvant targeted therapy before metastasectomy; but with an increase in surgical complications due to the effects of these new drugs in tissue healing. We have aimed to answer the question: Is there a role for systemic targeted therapy after surgical treatment for metastases of renal cell carcinoma? We have made a search in Pubmed database. As far as we know, evidence is low and it's based in case reports and small series of patients treated with adjuvant drugs after neoadjuvant therapy plus metastasectomy in cases of partial response to initial systemic treatment. Despite the limitations and high risk of bias, promising results and cases with long-term survival with this approach have been described. Two ongoing clinical trials may answer the question that concerns us.
    05/2015; 4(2):254-62. DOI:10.5527/wjn.v4.i2.254
  • Source
    [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.
    06/2012; 2012:250479. DOI:10.1155/2012/250479
  • 05/2014; 8(5-6):E398-412. DOI:10.5489/cuaj.1894