title: Active smoking may negatively affect response rate, progression-free survival, and overall survival of patients with metastatic renal cell carcinoma treated with sunitinib.
abstract: BACKGROUND
  Obesity, smoking, hypertension, and diabetes are risk factors for renal cell carcinoma development. Their presence has been associated with a worse outcome in various cancers. We sought to determine their association with outcome of sunitinib treatment in metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  An international multicenter retrospective study of sunitinib-treated mRCC patients was performed. Multivariate analyses were performed to determine the association between outcome and the pretreatment status of smoking, body mass index, hypertension, diabetes, and other known prognostic factors.
  
  
  RESULTS
  Between 2004 and 2013, 278 mRCC patients were treated with sunitinib: 59 were active smokers, 67 were obese, 73 were diabetic, and 165 had pretreatment hypertension. Median progression-free survival (PFS) was 9 months, and overall survival (OS) was 22 months. Factors associated with PFS were smoking status (past and active smokers: hazard ratio [HR]: 1.17, p = .39; never smokers: HR: 2.94, p < .0001), non-clear cell histology (HR: 1.62, p = .011), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 3.51, p < .0001), use of angiotensin system inhibitors (HR: 0.63, p = .01), sunitinib dose reduction or treatment interruption (HR: 0.72, p = .045), and Heng risk (good and intermediate risk: HR: 1.07, p = .77; poor risk: HR: 1.87, p = .046). Factors associated with OS were smoking status (past and active smokers: HR: 1.25, p = .29; never smokers: HR: 2.7, p < .0001), pretreatment neutrophil-to-lymphocyte ratio >3 (HR: 2.95, p < .0001), and sunitinib-induced hypertension (HR: 0.57, p = .002).
  
  
  CONCLUSIONS
  Active smoking may negatively affect the PFS and OS of sunitinib-treated mRCC. Clinicians should consider advising patients to quit smoking at initiation of sunitinib treatment for mRCC.
authors: Genitourinary Oncology Service, Institute of Oncology, Meir Medical Center and the Sackler School of Medicine, Tel Aviv University, Kfar-Saba, Israel; Department of Oncology, Rambam Medical Center, Haifa, Israel; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Roswell Park Cancer Institute, Buffalo, New York, USA; Department of Oncology, Wolfson Medical Center, Holon, Israel; Department of Oncology, Asaf Harofe Medical Center, Zerifin, Israel; Department of Oncology, Sheba Medical Center, Tel Hashomer, Israel; Department of Oncology, Soroka University Medical Center, Beer-sheva, Israel.
authors: Daniel
authors: D
authors: Keizman
authors: Maya
authors: M
authors: Gottfried
authors: Maya
authors: M
authors: Ish-Shalom
authors: Natalie
authors: N
authors: Maimon
authors: Avivit
authors: A
authors: Peer
authors: Avivit
authors: A
authors: Neumann
authors: Hans
authors: H
authors: Hammers
authors: Mario A
authors: MA
authors: Eisenberger
authors: Victoria
authors: V
authors: Sinibaldi
authors: Roberto
authors: R
authors: Pili
authors: Henry
authors: H
authors: Hayat
authors: Svetlana
authors: S
authors: Kovel
authors: Avishay
authors: A
authors: Sella
authors: Ben
authors: B
authors: Boursi
authors: Rony
authors: R
authors: Weitzen
authors: Wilmosh
authors: W
authors: Mermershtain
authors: Keren
authors: K
authors: Rouvinov
authors: Raanan
authors: R
authors: Berger
authors: Michael A
authors: MA
authors: Carducci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D000077210:Sunitinib; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Active smoking; Metastatic renal cell carcinoma; Outcome; Sunitinib treatment