title: The role of intratumoral therapy with cisplatin/epinephrine injectable gel in the management of advanced squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck.
  
  
  METHODS
  Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression.
  
  
  METHODS
  Tertiary referral centers in North America and Europe.
  
  
  METHODS
  One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck.
  
  
  METHODS
  Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire.
  
  
  METHODS
  Local tumor response and patient benefit attributable to improvements in tumor-related symptoms.
  
  
  RESULTS
  Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P<.001). Tumor response and patient benefit were significantly correlated (P=.006): 47% (17/36) of patients with target tumor responses achieved a rigorously defined benefit based on a prospectively selected treatment goal vs 15% (22/142) of nonresponders.
  
  
  CONCLUSIONS
  Cisplatin/epinephrine injectable gel reduces tumor burden, ameliorates tumor symptoms, and provides a new therapeutic option for treating patients with squamous cell carcinoma of the head and neck.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Northwestern University Medical School, Evanston Northwestern Healthcare, IL 60201, USA. b-wenig@nwu.edu
authors.forename: Barry L
authors.initials: BL
authors.lastname: Wenig
authors.forename: Jochen A
authors.initials: JA
authors.lastname: Werner
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Castro
authors.forename: Kasi S
authors.initials: KS
authors.lastname: Sridhar
authors.forename: Harinder S
authors.initials: HS
authors.lastname: Garewal
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kehrl
authors.forename: Anna
authors.initials: A
authors.lastname: Pluzanska
authors.forename: Olaf
authors.initials: O
authors.lastname: Arndt
authors.forename: Peter D
authors.initials: PD
authors.lastname: Costantino
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Mills
authors.forename: Frank R
authors.initials: FR
authors.lastname: Dunphy
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Orenberg
authors.forename: Richard D
authors.initials: RD
authors.lastname: Leavitt
mesh_terms: D000322:Adrenergic Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004837:Epinephrine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D005782:Gels; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D015552:Injections, Intralesional; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000322:Adrenergic Agonists; D000970:Antineoplastic Agents; D004338:Drug Combinations; D005782:Gels; D002945:Cisplatin; D004837:Epinephrine