title: Synergistic Survival: A New Phenomenon Connected to Adverse Events of First-Line Sunitinib Treatment in Advanced Renal Cell Carcinoma.
abstract: The aim was to assess the relationship between treatment efficacy and adverse events (AEs) for patients with advanced renal cell carcinoma treated with first-line sunitinib.
  
  
  
  274 patients were treated with sunitinib (50 mg/d, 4-weeks-on and 2-weeks-off schedule). Physical and laboratory evaluations were done every sixth week. AEs were diagnosed at every visit. Clinical response was assessed every 3 months. The objective response rate (ORR), median progression-free (mPFS) and median overall survival (mOS) and AEs were evaluated. Besides χ(2) and log rank tests, multivariate Cox regression analysis and for synergism 1-sided t tests were used.
  
  
  
  The ORR was 25%. After a median follow-up of 32 months, the mPFS and mOS were 9 and 19 months, respectively. Hypertension, diarrhea, hypothyroidism, mucositis, hand-foot syndrome (HFS), skin toxicity, and leukopenia were the most frequent treatment-associated AEs. Significantly longer (P < .01) mPFS and mOS were observed when hypertension, diarrhea, HFS, hypothyroidism, skin toxicity, or leukopenia occurred. A statistically significant synergistic effect of the listed AEs was observed for progression-free survival (P < .001) and overall survival (P < .001). Multivariate analysis revealed that besides the prognostic category, the higher number of AEs (3-6 vs. 0-2) was an independent marker of longer mPFS (24 vs. 5 months, respectively; P < .001) and mOS (51 vs. 9 months, respectively; P < .001).
  
  
  
  Results of this study provide evidence for the synergistically enhanced efficacy of sunitinib treatment in patients who present multiple AEs. These AEs are diagnosed routinely and their coexistence can help physicians to predict which group of patients would benefit the most from first-line sunitinib treatment.
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Krisztián
authors.initials: K
authors.lastname: Nagyiványi
authors.affiliation: National Institute of Oncology, Budapest, Hungary. Electronic address: budai@oncol.hu.
authors.forename: Barna
authors.initials: B
authors.lastname: Budai
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Bíró
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Gyergyay
authors.affiliation: Semmelweis University, Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Noszek
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Zsófia
authors.initials: Z
authors.lastname: Küronya
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Németh
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: National Institute of Oncology, Budapest, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Géczi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Advanced renal cell carcinoma; Adverse events; First-line sunitinib; Predictive marker; Synergistic survival