title: Favorable outcome in elderly Asian patients with metastatic renal cell carcinoma treated with everolimus: the Osaka Urologic Oncology Group.
abstract: BACKGROUND
  In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ≥ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice.
  
  
  METHODS
  172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients.
  
  
  RESULTS
  Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last follow- up. There were 86 (50%) patients ≥ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/ SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255- 0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life.
  
  
  CONCLUSIONS
  Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.
authors.affiliation: Department of Urology, Osaka Medical College, Takatsuki, Japan E-mail : uro004@poh.osaka-med.ac.jp.
authors.forename: Teruo
authors.initials: T
authors.lastname: Inamoto
authors.forename: Haruhito
authors.initials: H
authors.lastname: Azuma
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nakatani
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ueda
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Kinoshita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nishimura
authors.forename: Hiro-Omi
authors.initials: HO
authors.lastname: Kanayama
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Masao
authors.initials: M
authors.lastname: Tsujihata
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus