title: Impact of adverse events, treatment modifications, and dose intensity on survival among patients with advanced renal cell carcinoma treated with first-line sunitinib: a medical chart review across ten centers in five European countries.
abstract: Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥ 18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity.
authors.affiliation: IRCCS San Matteo University Hospital Foundation, Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Antonin
authors.initials: A
authors.lastname: Levy
authors.forename: Robert
authors.initials: R
authors.lastname: Hawkins
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Paul
authors.initials: P
authors.lastname: Nathan
authors.forename: Ray
authors.initials: R
authors.lastname: McDermott
authors.forename: John
authors.initials: J
authors.lastname: Wagstaff
authors.forename: Paul
authors.initials: P
authors.lastname: Donnellan
authors.forename: John
authors.initials: J
authors.lastname: McCaffrey
authors.forename: Francis
authors.initials: F
authors.lastname: Vekeman
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Neary
authors.forename: Jose
authors.initials: J
authors.lastname: Diaz
authors.forename: Faisal
authors.initials: F
authors.lastname: Mehmud
authors.forename: Mei Sheng
authors.initials: MS
authors.lastname: Duh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects*; D012189:Retrospective Studies; D000077210:Sunitinib; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Angiogenesis; clinical observations; statistical methods; urological oncology