title: Skin toxicity and quality of life in patients with metastatic colorectal cancer during first-line panitumumab plus FOLFIRI treatment in a single-arm phase II study.
abstract: BACKGROUND
  Integument-related toxicities are common during epidermal growth factor receptor (EGFR)-targeted therapy. Panitumumab is a fully human monoclonal antibody targeting the EGFR that significantly improves progression-free survival when added to chemotherapy in patients with metastatic colorectal cancer who have wild-type (WT) KRAS tumours. Primary efficacy and tolerability results from a phase II single-arm study of first-line panitumumab plus FOLFIRI in patients with metastatic colorectal cancer have been reported. Here we report additional descriptive tolerability and quality of life data from this trial.
  
  
  METHODS
  Integument-related toxicities and quality of life were analysed; toxicities were graded using modified National Cancer Institute Common Toxicity Criteria. Kaplan-Meier estimates of time to and duration of first integument-related toxicity were prepared. Quality of life was measured using EuroQoL EQ-5D and EORTC QLQ-C30. Best overall response was analysed by skin toxicity grade and baseline quality of life. Change in quality of life was analysed by skin toxicity severity.
  
  
  RESULTS
  154 patients were enrolled (WT KRAS n = 86; mutant KRAS n = 59); most (98%) experienced integument-related toxicities (most commonly rash [42%], dry skin [40%] and acne [36%]). Median time to first integument-related toxicity was 8 days; median duration was 334 days. Overall, proportionally more patients with grade 2+ skin toxicity responded (56%) compared with those with grade 0/1 (29%). Mean overall EQ-5D health state index scores (0.81 vs. 0.78), health rating scores (72.5 vs. 71.0) and QLQ-C30 global health status scores (65.8 vs. 66.7) were comparable at baseline vs. safety follow-up (8 weeks after completion), respectively and appeared unaffected by skin toxicity severity.
  
  
  CONCLUSIONS
  First-line panitumumab plus FOLFIRI has acceptable tolerability and appears to have little impact on quality of life, despite the high incidence of integument-related toxicity.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00508404.
authors.affiliation: Department of Internal Medicine IV - Haematology and Oncology, Hospital Wels-Grieskirchen, Wels, Austria. Josef.Thaler@klinikum-wegr.at
authors.forename: Josef
authors.initials: J
authors.lastname: Thaler
authors.forename: Meinolf
authors.initials: M
authors.lastname: Karthaus
authors.forename: Laurent
authors.initials: L
authors.lastname: Mineur
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Henry
authors.initials: H
authors.lastname: Letocha
authors.forename: Ralf
authors.initials: R
authors.lastname: Hofheinz
authors.forename: Eva
authors.initials: E
authors.lastname: Fernebro
authors.forename: Erick
authors.initials: E
authors.lastname: Gamelin
authors.forename: Ana
authors.initials: A
authors.lastname: Baños
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Köhne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D011905:Genes, ras; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D000077544:Panitumumab; D011788:Quality of Life; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin