title: Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial.
abstract: BACKGROUND
  The AIO KRK-0104 randomised phase II trial investigated the efficacy and safety of two capecitabine-based regimens: combination of capecitabine and irinotecan (CAPIRI) plus cetuximab (CAPIRI-C) and combination of capecitabine with oxaliplatin (CAPOX) plus cetuximab (CAPOX-C) in the first-line treatment of metastatic colorectal cancer (mCRC). Treatment-related skin toxicity (ST) was evaluated separately for capecitabine and cetuximab. The present analysis investigates the correlation of capecitabine-attributed ST (Cape-ST) and parameters of treatment efficacy.
  
  
  METHODS
  Patients with mCRC were randomised to cetuximab (400 mg m(-2), day 1, followed by 250 mg m(-2) weekly) plus CAPIRI (irinotecan 200 mg m(-2), day 1; capecitabine 800 mg m(-2), twice daily, days 1-14, every 3 weeks), or cetuximab plus CAPOX (oxaliplatin 130 mg m(-2), day 1; capecitabine 1000 mg m(-2), twice daily, days 1-14, every 3 weeks).
  
  
  RESULTS
  Of 185 recruited patients, 149 (CAPIRI-C, n=78; CAPOX-C, n=71) received study treatment beyond the first tumour assessment and were evaluable for efficacy. Capecitabine-attributed ST, predominantly hand-foot syndrome, was observed in 32.2% of patients. Capecitabine-attributed ST grade 1-3 was associated with a significantly higher disease control rate (DCR) (97.9 vs 86.1%, P=0.038) compared with grade 0 toxicity. Moreover, Cape-ST grade 1-3 related to a markedly longer progression-free survival (PFS) (9.9 vs 5.6 months, P<0.001) and overall survival (OS) (32.8 vs 22.4 months, P=0.008). Separate analyses of treatment arms indicated that the effect of Cape-ST on PFS remained significant for both arms, whereas the effect on OS remained apparent as a strong trend.
  
  
  CONCLUSIONS
  This analysis supports the hypothesis that for the evaluated regimens, a correlation exists between Cape-ST and treatment efficacy regarding DCR, PFS, and OS.
authors.affiliation: Medical Department III, University of Munich, Klinikum Muenchen-Grosshadern, Marchioninistrasse 15, D-81377 Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stintzing
authors.forename: L
authors.initials: L
authors.lastname: Fischer von Weikersthal
authors.forename: U
authors.initials: U
authors.lastname: Vehling-Kaiser
authors.forename: M
authors.initials: M
authors.lastname: Stauch
authors.forename: H G
authors.initials: HG
authors.lastname: Hass
authors.forename: H
authors.initials: H
authors.lastname: Dietzfelbinger
authors.forename: D
authors.initials: D
authors.lastname: Oruzio
authors.forename: S
authors.initials: S
authors.lastname: Klein
authors.forename: K
authors.initials: K
authors.lastname: Zellmann
authors.forename: T
authors.initials: T
authors.lastname: Decker
authors.forename: M
authors.initials: M
authors.lastname: Schulze
authors.forename: W
authors.initials: W
authors.lastname: Abenhardt
authors.forename: G
authors.initials: G
authors.lastname: Puchtler
authors.forename: H
authors.initials: H
authors.lastname: Kappauf
authors.forename: J
authors.initials: J
authors.lastname: Mittermüller
authors.forename: C
authors.initials: C
authors.lastname: Haberl
authors.forename: C
authors.initials: C
authors.lastname: Giessen
authors.forename: N
authors.initials: N
authors.lastname: Moosmann
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D000068818:Cetuximab; D002986:Clinical Trials as Topic / Q000379:methods; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005858:Germany; D006801:Humans; D015994:Incidence; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012871:Skin Diseases / Q000139:chemically induced* / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin