Management of Older Patients With Metastatic Renal Cell Carcinoma Receiving Sunitinib: A Hypothetical, Illustrative Case Scenario

CASE STUDY Tom, a 75-year-old white male, was recently diagnosed with metastatic renal cell carcinoma (RCC; Tom’s case is not an actual clinical case but has been developed by the authors as an exemplar). Two years prior, he had undergone a left partial (laparoscopic) nephrectomy for clear cell RCC. At that time, he had a stage 3 disease (the tumor extended into perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia [Cancer.net, 2016]), and regularly (every 3–6 months) scheduled surveillance imaging did not show metastatic disease. Recent imaging with a computed tomography (CT) of the chest/abdomen/pelvis revealed small bilateral pulmonary nodules that did not have the radiographic appearance of a primary lung tumor, but rather that of metastatic disease. Therefore, a decision was made to repeat CT scans in a shorter interval (in 6 weeks) to assess growth kinetics. Subsequent CT scan showed an increase in size and number of pulmonary nodules, so the decision was made to begin systemic treatment. At the time of Tom’s metastatic evaluation, his Eastern Cooperative Oncology Group performance status was 0 as he was asymptomatic and fully active (Table 1). He was classified as favorable risk according to Heng criteria (Table 2). Tom is married and lives with his wife. He is independent in his self-care but also relies on his wife for health-care decision-making. He does not drink alcohol and is a former smoker with a history of 30 pack-years. Tom’s medical history includes hypertension that is adequately controlled with lisinopril (20 mg/day), coronary artery disease (on daily aspirin 81 mg) with left ventricular ejection fraction (LVEF) of > 50%, which is within the normal range (50%–75%), benign prostatic hyperplasia for which he is treated with finasteride, and hyperlipidemia that is treated with atorvastatin.

[1]  Versione,et al.  Common Terminology Criteria for Adverse Events , 2020, Definitions.

[2]  R. Motzer,et al.  Population Pharmacokinetic/Pharmacodynamic Modeling of Sunitinib by Dosing Schedule in Patients with Advanced Renal Cell Carcinoma or Gastrointestinal Stromal Tumor , 2016, Clinical Pharmacokinetics.

[3]  F. Boccardo,et al.  Treatment of elderly patients with metastatic renal cell carcinoma , 2016, Expert review of anticancer therapy.

[4]  F. Kabbinavar,et al.  Metastatic clear cell renal cell carcinoma: A review of current therapies and novel immunotherapies. , 2015, Critical reviews in oncology/hematology.

[5]  Mellar P. Davis,et al.  Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients , 2015, British Journal of Cancer.

[6]  U. Harmenberg,et al.  Cancer Characteristics and Current Treatments of Patients with Renal Cell Carcinoma in Sweden , 2015, BioMed research international.

[7]  I. Christensen,et al.  A five-factor biomarker profile obtained week 4–12 of treatment for improved prognostication in metastatic renal cell carcinoma: Results from DARENCA study 2 , 2015, Acta oncologica.

[8]  M. Fishman,et al.  Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma. , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  V. Muglia,et al.  Renal cell carcinoma: histological classification and correlation with imaging findings* , 2015, Radiologia brasileira.

[10]  T. Choueiri,et al.  Efficacy of targeted therapy for metastatic renal cell carcinoma in the elderly patient population. , 2014, Clinical genitourinary cancer.

[11]  A. Masumoto,et al.  Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma. , 2014, World journal of gastroenterology.

[12]  S. Pal,et al.  Adjuvant therapy for renal cell carcinoma: past, present, and future. , 2014, The oncologist.

[13]  Y. Najjar,et al.  A 2 weeks on and 1 week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma. , 2014, European journal of cancer.

[14]  Kazuhiko Yoshida,et al.  Superior tolerability of altered dosing schedule of sunitinib with 2-weeks-on and 1-week-off in patients with metastatic renal cell carcinoma--comparison to standard dosing schedule of 4-weeks-on and 2-weeks-off. , 2014, Japanese journal of clinical oncology.

[15]  T. Bathala,et al.  Adult UrologyOncology: Adrenal/Renal/Upper Tract/BladderClinical Outcomes for Patients with Metastatic Renal Cell Carcinoma Treated with Alternative Sunitinib Schedules , 2014 .

[16]  R. Figlin,et al.  Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma , 2014, British Journal of Cancer.

[17]  M. Gore,et al.  Prognostic factors for survival in 1059 patients treated with sunitinib for metastatic renal cell carcinoma , 2013, British Journal of Cancer.

[18]  A. Poprach,et al.  Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[19]  G. Procopio,et al.  Re: Camillo Porta, Emiliano Calvo, Miguel A. Climent, et al. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. Eur Urol 2012;61:826-33. , 2012, European urology.

[20]  K. Scher,et al.  Under-representation of older adults in cancer registration trials: known problem, little progress. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  C. Porta,et al.  Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. , 2012, European urology.

[22]  O. Rigal,et al.  Severe clinical toxicities are correlated with survival in patients with advanced renal cell carcinoma treated with sunitinib and sorafenib , 2011, British Journal of Cancer.

[23]  R. Figlin,et al.  Response: Re: Hypertension as a Biomarker of Efficacy in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib , 2011 .

[24]  A. Ravaud,et al.  Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): final analysis of overall survival. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Wanling Xie,et al.  Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  C. Porta,et al.  Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. , 2009, The Lancet. Oncology.

[27]  L. Schwartz,et al.  NCCN clinical practice guidelines in oncology: kidney cancer. , 2009, Journal of the National Comprehensive Cancer Network : JNCCN.

[28]  David McDermott,et al.  Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. , 2007, The New England journal of medicine.

[29]  R. Pazdur,et al.  Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  E. McFadden,et al.  Toxicity and response criteria of the Eastern Cooperative Oncology Group , 1982, American journal of clinical oncology.

[31]  H. Burstein,et al.  NCCN CLINICAL PRACTICE GUIDELINES IN ONCOLOGY , 2019 .