Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery

Jonathan L. Silberstein, Frederick Millard, Reza Mehrazin, Ryan Kopp, Wassim Bazzi, Christopher J. Diblasio, Anthony Patterson, Tracy M. Downs, Furhan Yunus, Christopher J. Kane, Ithaar H. Derweesh

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Abstract

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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 m2 (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. CONCLUSIONS: 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.

Original languageEnglish (US)
Pages (from-to)1270-1276
Number of pages7
JournalBJU International
Volume106
Issue number9
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

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Nephrons
Protein-Tyrosine Kinases
Neoplasms
Dialysis
Kidney
Therapeutics
sunitinib
Metastasectomy
Warm Ischemia
Tumor Burden
Glomerular Filtration Rate
Renal Cell Carcinoma
Creatinine
Demography
Prospective Studies
Pathology
Biopsy

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Silberstein, J. L., Millard, F., Mehrazin, R., Kopp, R., Bazzi, W., Diblasio, C. J., ... Derweesh, I. H. (2010). Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. BJU International, 106(9), 1270-1276. https://doi.org/10.1111/j.1464-410X.2010.09357.x

Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. / Silberstein, Jonathan L.; Millard, Frederick; Mehrazin, Reza; Kopp, Ryan; Bazzi, Wassim; Diblasio, Christopher J.; Patterson, Anthony; Downs, Tracy M.; Yunus, Furhan; Kane, Christopher J.; Derweesh, Ithaar H.

In: BJU International, Vol. 106, No. 9, 01.11.2010, p. 1270-1276.

Research output: Contribution to journalArticle

Silberstein, JL, Millard, F, Mehrazin, R, Kopp, R, Bazzi, W, Diblasio, CJ, Patterson, A, Downs, TM, Yunus, F, Kane, CJ & Derweesh, IH 2010, 'Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery', BJU International, vol. 106, no. 9, pp. 1270-1276. https://doi.org/10.1111/j.1464-410X.2010.09357.x
Silberstein JL, Millard F, Mehrazin R, Kopp R, Bazzi W, Diblasio CJ et al. Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. BJU International. 2010 Nov 1;106(9):1270-1276. https://doi.org/10.1111/j.1464-410X.2010.09357.x
Silberstein, Jonathan L. ; Millard, Frederick ; Mehrazin, Reza ; Kopp, Ryan ; Bazzi, Wassim ; Diblasio, Christopher J. ; Patterson, Anthony ; Downs, Tracy M. ; Yunus, Furhan ; Kane, Christopher J. ; Derweesh, Ithaar H. / Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. In: BJU International. 2010 ; Vol. 106, No. 9. pp. 1270-1276.
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AU - Silberstein, Jonathan L.

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AU - Mehrazin, Reza

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AU - Bazzi, Wassim

AU - Diblasio, Christopher J.

AU - Patterson, Anthony

AU - Downs, Tracy M.

AU - Yunus, Furhan

AU - Kane, Christopher J.

AU - Derweesh, Ithaar H.

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N2 - OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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 m2 (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. CONCLUSIONS: 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.

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