title: Absence of Significant Correlation of Adverse Events Between First- and Second-Line Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma.
abstract: Several adverse events (AEs) are known to be commonly observed during treatment with different tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) patients. However, no significant correlation appears present in the profiles of such AEs between first- and second-line TKI therapies. Therefore, a second-line targeted agent for patients with mRCC could be selected irrespective of the AE profile during first-line TKI therapy.
  
  
  BACKGROUND
  Several adverse events (AEs) commonly observed during treatment with different tyrosine kinase inhibitors (TKIs). The objective of the present study was to investigate whether the appearance of such AEs during treatment with first-line TKIs significantly affects the occurrence of AEs during second-line TKI therapy for patients with metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  The present study included 154 consecutive patients with mRCC treated with second-line TKIs after the discontinuation of first-line TKIs. The association of AEs, including diarrhea, fatigue, hand-foot syndrome, hypertension, and hypothyroidism, between first- and second-line therapies was analyzed in these 154 patients.
  
  
  RESULTS
  For all 5 AEs assessed in the present study, the proportion of patients experiencing AEs or those grade ≥ 3 during second-line TKI therapy was not significantly different among the following 3 groups: patients without AEs, those with grade ≤ 2 AEs, and those with grade ≥ 3 AEs during first-line TKI therapy. Furthermore, no significant difference was seen in progression-free or overall survival after the introduction of second-line TKIs between patients with and without grade ≥ 3 AEs during treatment with first-line TKIs.
  
  
  CONCLUSIONS
  The incidence of AEs or grade ≥ 3 AEs during second-line TKI therapy are not dependent on the profiles of AEs during first-line TKI therapy in patients with mRCC. Therefore, AEs that occur during first-line TKI therapy should not affect the selection of second-line targeted agents for patients with mRCC.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: hideakimiyake@hotmail.com.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imai
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077784:Axitinib; D000077210:Sunitinib
keywords: Adverse events; First-line; Metastatic renal cell carcinoma; Second-line; Tyrosine kinase inhibitors