Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? A comparison of primary and adjuvant approaches

Nishant Patel, Jason Woo, Michael A. Liss, Kerrin L. Palazzi, J. Michael Randall, Reza Mehrazin, Ramzi Jabaji, Hossein S. Mirheydar, Kyle Gillis, Hak J. Lee, Anthony Patterson, Christopher J. Kane, Frederick Millard, Ithaar H. Derweesh

Research output: Contribution to journalArticle

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Abstract

Introduction: To compare surgical complications and tyrosine kinase inhibitor (TKI)-toxicities in patients who underwent primary cytoreductive nephrectomy (CN) followed by adjuvant TKI therapy versus those who underwent neoadjuvant TKI therapy prior to planned CN for metastatic renal cell carcinoma (mRCC). Materials and methods: Two-center retrospective analysis. Sixty-one mRCC patients underwent TKI therapy with sunitinib between July 2007 to January 2014. Patients were divided into three groups: Primary CN followed by adjuvant TKI (n = 27, Group 1), neoadjuvant TKI prior to CN (n = 21, Group 2), and primary TKI alone (no surgery, n = 13, Group 3). Primary outcome was frequency and severity of surgical complications (Clavien). Secondary outcome was frequency and severity of TKI-related toxicities (NIH Common Toxicity Criteria). Multivariable analysis was carried out for factors associated with complications. Results: There were no significant differences in demographics, ECOG status, and median number TKI cycles (p = 0.337). Mean tumor size (cm) was larger in Group 3 (12.8) than Group 2 (8.9) and Group 1 (9.3), p = 0.014. TKI-related toxicities occurred in 100%, 90.5%, and 88.9% in Group 3, Group 2, and Group 1 (p = 0.469). There was no difference in incidence of high grade (p = 0.967) and low grade (p = 0.380) TKI-toxicities. Overall surgical complication rate was similar between Group 2 (47.6%) and Group 1 (33.3%), p = 0.380. Group 2 had more high grade surgical complications (28.6%) than Group 1 (0%), p = 0.004. Multivariable analysis demonstrated increasing age was independently associated with development of surgical complications (HR 1.059, p = 0.040). Conclusion: Patients receiving neoadjuvant TKI therapy prior to CN experienced more high grade surgical complications than patients who underwent primary CN. Potential for increased high grade surgical complications requires further investigation and may impact pretreatment counseling.

Original languageEnglish (US)
Pages (from-to)8227-8233
Number of pages7
JournalCanadian Journal of Urology
Volume23
Issue number2
StatePublished - Jan 1 2016

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Renal Cell Carcinoma
Protein-Tyrosine Kinases
Nephrectomy
Therapeutics
TYK2 Kinase
Counseling
Demography
Incidence

All Science Journal Classification (ASJC) codes

  • Urology

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Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? A comparison of primary and adjuvant approaches. / Patel, Nishant; Woo, Jason; Liss, Michael A.; Palazzi, Kerrin L.; Randall, J. Michael; Mehrazin, Reza; Jabaji, Ramzi; Mirheydar, Hossein S.; Gillis, Kyle; Lee, Hak J.; Patterson, Anthony; Kane, Christopher J.; Millard, Frederick; Derweesh, Ithaar H.

In: Canadian Journal of Urology, Vol. 23, No. 2, 01.01.2016, p. 8227-8233.

Research output: Contribution to journalArticle

Patel, N, Woo, J, Liss, MA, Palazzi, KL, Randall, JM, Mehrazin, R, Jabaji, R, Mirheydar, HS, Gillis, K, Lee, HJ, Patterson, A, Kane, CJ, Millard, F & Derweesh, IH 2016, 'Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? A comparison of primary and adjuvant approaches', Canadian Journal of Urology, vol. 23, no. 2, pp. 8227-8233.
Patel, Nishant ; Woo, Jason ; Liss, Michael A. ; Palazzi, Kerrin L. ; Randall, J. Michael ; Mehrazin, Reza ; Jabaji, Ramzi ; Mirheydar, Hossein S. ; Gillis, Kyle ; Lee, Hak J. ; Patterson, Anthony ; Kane, Christopher J. ; Millard, Frederick ; Derweesh, Ithaar H. / Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? A comparison of primary and adjuvant approaches. In: Canadian Journal of Urology. 2016 ; Vol. 23, No. 2. pp. 8227-8233.
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abstract = "Introduction: To compare surgical complications and tyrosine kinase inhibitor (TKI)-toxicities in patients who underwent primary cytoreductive nephrectomy (CN) followed by adjuvant TKI therapy versus those who underwent neoadjuvant TKI therapy prior to planned CN for metastatic renal cell carcinoma (mRCC). Materials and methods: Two-center retrospective analysis. Sixty-one mRCC patients underwent TKI therapy with sunitinib between July 2007 to January 2014. Patients were divided into three groups: Primary CN followed by adjuvant TKI (n = 27, Group 1), neoadjuvant TKI prior to CN (n = 21, Group 2), and primary TKI alone (no surgery, n = 13, Group 3). Primary outcome was frequency and severity of surgical complications (Clavien). Secondary outcome was frequency and severity of TKI-related toxicities (NIH Common Toxicity Criteria). Multivariable analysis was carried out for factors associated with complications. Results: There were no significant differences in demographics, ECOG status, and median number TKI cycles (p = 0.337). Mean tumor size (cm) was larger in Group 3 (12.8) than Group 2 (8.9) and Group 1 (9.3), p = 0.014. TKI-related toxicities occurred in 100{\%}, 90.5{\%}, and 88.9{\%} in Group 3, Group 2, and Group 1 (p = 0.469). There was no difference in incidence of high grade (p = 0.967) and low grade (p = 0.380) TKI-toxicities. Overall surgical complication rate was similar between Group 2 (47.6{\%}) and Group 1 (33.3{\%}), p = 0.380. Group 2 had more high grade surgical complications (28.6{\%}) than Group 1 (0{\%}), p = 0.004. Multivariable analysis demonstrated increasing age was independently associated with development of surgical complications (HR 1.059, p = 0.040). Conclusion: Patients receiving neoadjuvant TKI therapy prior to CN experienced more high grade surgical complications than patients who underwent primary CN. Potential for increased high grade surgical complications requires further investigation and may impact pretreatment counseling.",
author = "Nishant Patel and Jason Woo and Liss, {Michael A.} and Palazzi, {Kerrin L.} and Randall, {J. Michael} and Reza Mehrazin and Ramzi Jabaji and Mirheydar, {Hossein S.} and Kyle Gillis and Lee, {Hak J.} and Anthony Patterson and Kane, {Christopher J.} and Frederick Millard and Derweesh, {Ithaar H.}",
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T1 - Does timing of targeted therapy for metastatic renal cell carcinoma impact treatment toxicity and surgical complications? A comparison of primary and adjuvant approaches

AU - Patel, Nishant

AU - Woo, Jason

AU - Liss, Michael A.

AU - Palazzi, Kerrin L.

AU - Randall, J. Michael

AU - Mehrazin, Reza

AU - Jabaji, Ramzi

AU - Mirheydar, Hossein S.

AU - Gillis, Kyle

AU - Lee, Hak J.

AU - Patterson, Anthony

AU - Kane, Christopher J.

AU - Millard, Frederick

AU - Derweesh, Ithaar H.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Introduction: To compare surgical complications and tyrosine kinase inhibitor (TKI)-toxicities in patients who underwent primary cytoreductive nephrectomy (CN) followed by adjuvant TKI therapy versus those who underwent neoadjuvant TKI therapy prior to planned CN for metastatic renal cell carcinoma (mRCC). Materials and methods: Two-center retrospective analysis. Sixty-one mRCC patients underwent TKI therapy with sunitinib between July 2007 to January 2014. Patients were divided into three groups: Primary CN followed by adjuvant TKI (n = 27, Group 1), neoadjuvant TKI prior to CN (n = 21, Group 2), and primary TKI alone (no surgery, n = 13, Group 3). Primary outcome was frequency and severity of surgical complications (Clavien). Secondary outcome was frequency and severity of TKI-related toxicities (NIH Common Toxicity Criteria). Multivariable analysis was carried out for factors associated with complications. Results: There were no significant differences in demographics, ECOG status, and median number TKI cycles (p = 0.337). Mean tumor size (cm) was larger in Group 3 (12.8) than Group 2 (8.9) and Group 1 (9.3), p = 0.014. TKI-related toxicities occurred in 100%, 90.5%, and 88.9% in Group 3, Group 2, and Group 1 (p = 0.469). There was no difference in incidence of high grade (p = 0.967) and low grade (p = 0.380) TKI-toxicities. Overall surgical complication rate was similar between Group 2 (47.6%) and Group 1 (33.3%), p = 0.380. Group 2 had more high grade surgical complications (28.6%) than Group 1 (0%), p = 0.004. Multivariable analysis demonstrated increasing age was independently associated with development of surgical complications (HR 1.059, p = 0.040). Conclusion: Patients receiving neoadjuvant TKI therapy prior to CN experienced more high grade surgical complications than patients who underwent primary CN. Potential for increased high grade surgical complications requires further investigation and may impact pretreatment counseling.

AB - Introduction: To compare surgical complications and tyrosine kinase inhibitor (TKI)-toxicities in patients who underwent primary cytoreductive nephrectomy (CN) followed by adjuvant TKI therapy versus those who underwent neoadjuvant TKI therapy prior to planned CN for metastatic renal cell carcinoma (mRCC). Materials and methods: Two-center retrospective analysis. Sixty-one mRCC patients underwent TKI therapy with sunitinib between July 2007 to January 2014. Patients were divided into three groups: Primary CN followed by adjuvant TKI (n = 27, Group 1), neoadjuvant TKI prior to CN (n = 21, Group 2), and primary TKI alone (no surgery, n = 13, Group 3). Primary outcome was frequency and severity of surgical complications (Clavien). Secondary outcome was frequency and severity of TKI-related toxicities (NIH Common Toxicity Criteria). Multivariable analysis was carried out for factors associated with complications. Results: There were no significant differences in demographics, ECOG status, and median number TKI cycles (p = 0.337). Mean tumor size (cm) was larger in Group 3 (12.8) than Group 2 (8.9) and Group 1 (9.3), p = 0.014. TKI-related toxicities occurred in 100%, 90.5%, and 88.9% in Group 3, Group 2, and Group 1 (p = 0.469). There was no difference in incidence of high grade (p = 0.967) and low grade (p = 0.380) TKI-toxicities. Overall surgical complication rate was similar between Group 2 (47.6%) and Group 1 (33.3%), p = 0.380. Group 2 had more high grade surgical complications (28.6%) than Group 1 (0%), p = 0.004. Multivariable analysis demonstrated increasing age was independently associated with development of surgical complications (HR 1.059, p = 0.040). Conclusion: Patients receiving neoadjuvant TKI therapy prior to CN experienced more high grade surgical complications than patients who underwent primary CN. Potential for increased high grade surgical complications requires further investigation and may impact pretreatment counseling.

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