title: Pan Canadian Rash Trial: A Randomized Phase III Trial Evaluating the Impact of a Prophylactic Skin Treatment Regimen on Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Induced Skin Toxicities in Patients With Metastatic Lung Cancer.
abstract: OBJECTIVE
  Erlotinib is an epidermal growth factor receptor inhibitor approved for patients with advanced non-small-cell lung cancer (NSCLC) whose epidermal growth factor receptor expression status is positive or unknown. Although it is efficacious, erlotinib can cause skin toxicity. This prospective, randomized phase III trial examined the effect of prophylactic treatment of erlotinib-induced skin rash.
  
  
  METHODS
  Patients receiving erlotinib in the second- or third-line setting for advanced NSCLC were randomly assigned to prophylactic minocycline (100 mg twice per day for 4 weeks), reactive treatment (after rash developed, per grade of rash), or no treatment unless severe (grade 3). Rash incidence and severity, time to maximal rash, time to resolution, and overall survival (OS) were compared among treatment groups.
  
  
  RESULTS
  In all, 150 patients were randomly assigned, 50 to each of three treatment arms. The incidence of skin toxicity was 84% regardless of treatment arm. Prophylactic treatment with minocycline significantly lengthened the time to the most severe grade of rash. Grade 3 rash was significantly higher in the no-treatment arm. OS was not significantly different among treatment arms, but patients receiving prophylactic or reactive treatments had a longer OS (7.6 and 8 months, respectively) than those who received no rash treatment (6 months). Rash was not self-limiting.
  
  
  CONCLUSIONS
  The incidence of all grades of rash did not differ statistically among the three arms, so the trial was negative. The incidence of grade 3 skin toxicities was reduced in patients who were treated with prophylactic minocycline or reactive treatment. Efficacy was not compromised. Prophylactic minocycline and reactive treatment are both acceptable options for the necessary treatment of erlotinib-induced rash in the second- or third-line setting of metastatic NSCLC.
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada. bmelosky@bccancer.bc.ca.
authors.forename: Barbara
authors.initials: B
authors.lastname: Melosky
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Helen
authors.initials: H
authors.lastname: Anderson
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Burkes
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Quincy
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Desiree
authors.initials: D
authors.lastname: Hao
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ho
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ho
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Lam
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Leighl
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Nevin
authors.initials: N
authors.lastname: Murray
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sun
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Winston
authors.affiliation: Barbara Melosky, Vincent Ho, Cheryl Ho, Nevin Murray, Sophie Sun, and Janessa J. Laskin, British Columbia Cancer Agency (BCCA) Vancouver Centre, Vancouver; Helen Anderson, BCCA Vancouver Island Centre, Victoria; Wendy Lam, Burnaby Regional Hospital, Burnaby; Christopher W. Lee, BCCA Fraser Valley Cancer Centre, Surrey; Robert Winston, BCCA Abbotsford Centre, Abbotsford, British Columbia; Ronald L. Burkes, Mount Sinai Hospital; Natasha B. Leighl, Princess Margaret Cancer Centre, Toronto, Ontario; Quincy Chu, Cross Cancer Institute, Edmonton; and Desiree Hao, Tom Baker Care Centre, Calgary, Alberta, Canada.
authors.forename: Janessa J
authors.initials: JJ
authors.lastname: Laskin
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects*; D005076:Exanthema / Q000209:etiology* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000008:administration & dosage*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; D008911:Minocycline