title: Risk Factors Exacerbating Hand-Foot Skin Reaction Induced by Capecitabine plus Oxaliplatin with or without Bevacizumab Therapy.
abstract: BACKGROUND
  Capecitabine plus oxaliplatin (CapeOx) ± bevacizumab therapy is associated with a high incidence of hand-foot skin reaction (HFSR), hindering treatment. However, timing of onset and risk factors remain unclear.
  
  
  OBJECTIVE
  This study examined the development of HFSR and risk factors for its exacerbation to a serious condition in CapeOx ± bevacizumab therapy.
  
  
  METHODS
  We retrospectively examined patients with colorectal cancer receiving CapeOx ± bevacizumab therapy between October 1, 2009, and March 31, 2012. The observation period was defined as lasting until completion of 8 cycles. The relationship between cumulative dose of capecitabine and cumulative proportion of patients developing HFSR was evaluated by Kaplan-Meier methods. Risk factors for exacerbation of HFSR to a serious condition were assessed by multiple logistic regression.
  
  
  RESULTS
  Data for 203 patients were analyzed. For patients treated at cumulative capecitabine doses of 100 000 mg/m(2) and 200 000 mg/m(2), Grade 1 HFSR occurred in ≥80% and ≥90%, respectively, and moderate-to-severe HFSR (Grade 2+) occurred in ≥10% and ≥20%, respectively. Multivariate analysis showed significant associations with diabetes (odds ratio [OR] = 4.79; 95% confidence interval [CI] = 1.86-12.34; P = 0.001), concomitant use of bevacizumab (OR = 6.01; 95% CI = 2.20-16.41; P = 0.001), history of fluorinated pyrimidine administration (OR = 2.42; 95% CI = 1.10-5.33; P = 0.027), and early onset (within 21 days) of Grade 1 HFSR (OR = 3.78; 95% CI = 1.64-8.70; P = 0.001).
  
  
  CONCLUSIONS
  HFSR in CapeOx therapy is a cumulative toxicity and risk of exacerbation to a serious condition increases with diabetes, concomitant use of bevacizumab, history of fluorinated pyrimidine administration, and onset of Grade 1 HFSR within 21 days.
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan takashi.yokokawa@jfcr.or.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokokawa
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Mae
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugita
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D060831:Hand-Foot Syndrome / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012307:Risk Factors
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil
keywords: CapeOx; bevacizumab; diabetes; hand-foot skin reaction; risk factor; capecitabine