title: Co-occurring adverse events enable early prediction of progression-free survival in metastatic renal cell carcinoma patients treated with sunitinib: a hypothesis-generating study.
abstract: OBJECTIVE
  Clinical practice shows significant differences in treatment outcomes and toxicity of sunitinib across patients. This retrospective study assessed early predictive markers for progression-free survival (PFS) in patients with metastatic clear cell renal cell carcinoma (RCC) treated with sunitinib in the first-line setting.
  
  
  METHODS
  We evaluated 28 patients with stage IV clear cell RCC (with good or intermediate MSKCC risk prognosis) treated at the Department of Oncology, University Hospital, Cracow between 2008 and 2013. Data included demographic profiles, adverse events during first cycle of therapy, treatment delays, and treatment outcomes. Sunitinib was administered on a standard schedule (50 mg/day, 4 weeks on, 2 weeks off). PFS values were estimated with the Kaplan-Meier method and compared using the log-rank test; we identified independent PFS predictors using multiple Cox regression models.
  
  
  RESULTS
  PFS was significantly longer in patients who experienced at least 1 adverse event after the first cycle of sunitinib (median 17.6 months vs. 5.6; p = 0.006). Hypertension and hand-foot syndrome were significantly correlated with longer PFS (29.3 vs. 6.0 months; p = 0.002, and not reached vs. 9.8 months; p = 0.002, respectively). We observed a similar (though not significant) tendency for neutropenia (17.5 vs. 8.4 months; p = 0.055). In multiple Cox regression, hypertension was the only individual independent predictor of PFS, but the co-occurrence of any 2 or 3 sunitinib-induced adverse events also predicted longer survival.
  
  
  CONCLUSIONS
  Although small, our study suggests that hypertension and hand-foot syndrome predict longer PFS in patients with clear cell RCC treated with sunitinib. The co-occurrence of 2 or more side effects seems also a significant predictor of longer survival. Larger studies are warranted to confirm the correlation between co-occurring side effects and PFS.
authors.affiliation: 1 Department of Oncology, University Hospital in Cracow, Cracow - Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kucharz
authors.forename: Paulina
authors.initials: P
authors.lastname: Dumnicka
authors.forename: Marek
authors.initials: M
authors.lastname: Kuzniewski
authors.forename: Beata
authors.initials: B
authors.lastname: Kusnierz-Cabala
authors.forename: Roman Maria
authors.initials: RM
authors.lastname: Herman
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Krzemieniecki
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects*; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib