title: Sequential use of mammalian target of rapamycin inhibitors in patients with metastatic renal cell carcinoma following failure of tyrosine kinase inhibitors.
abstract: The aim of the study is to evaluate the clinical experience of the sequential use of mammalian target of rapamycin inhibitors (mTORIs) for metastatic renal cell carcinoma (mRCC) refractory to tyrosine kinase inhibitors (TKIs). This study retrospectively investigated the clinical outcomes in a total of 83 consecutive Japanese patients with mRCC who were treated with either everolimus or temsirolimus following the failure of sorafenib and/or sunitinib. Of the 83 patients, 15, 61, and 7 were classified into favorable-, intermediate-, and poor-risk groups, respectively, according to the Memorial Sloan-Kettering Cancer Center model, and 47 and 36 patients were administered mTORIs as second- and third-line therapy, respectively. As the best responses to mTORIs, 6, 53, and 24 were judged to have a partial response, stable disease, and progressive disease, respectively. The median progression-free survival (PFS) and overall survival (OS) of these patients following the introduction of mTORIs were 5.8 and 20.4 months, respectively. Of the several factors examined, liver metastasis and pretreatment C-reactive protein (CRP) level were shown to be independently associated with PFS, while only pretreatment CRP level had an independent impact on OS. Adverse events related to mTORIs corresponding to ≥grade 3 were observed in 26 patients, including anemia in 7, pneumonitis in 7, neutropenia in 4, and stomatitis in 3. Despite the low response rate, mTORIs are well tolerated and could provide comparatively favorable prognostic outcomes in Japanese patients with mRCC after the failure of TKIs.
authors.affiliation: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kumano
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyake
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Harada
authors.forename: Masato
authors.initials: M
authors.lastname: Fujisawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D002097:C-Reactive Protein / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D002097:C-Reactive Protein; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases