title: Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma.
abstract: OBJECTIVE
  Treatment options for metastatic melanoma are limited. We conducted this phase II trial to assess the efficacy of JS1/34.5-/47-/granulocyte-macrophage colony-stimulating factor (GM-CSF) in stages IIIc and IV disease.
  
  
  METHODS
  Treatment involved intratumoral injection of up to 4 mL of 10(6) pfu/mL of JS1/34.5-/47-/GM-CSF followed 3 weeks later by up to 4 mL of 10(8) pfu/mL every 2 weeks for up to 24 treatments. Clinical activity (by RECIST [Response Evaluation Criteria in Solid Tumors]), survival, and safety parameters were monitored.
  
  
  RESULTS
  Fifty patients (stages IIIc, n = 10; IVM1a, n = 16; IVM1b, n = 4; IVM1c, n = 20) received a median of six injection sets; 74% of patients had received one or more nonsurgical prior therapies for active disease, including dacarbazine/temozolomide or interleukin-2 (IL-2). Adverse effects were limited primarily to transient flu-like symptoms. The overall response rate by RECIST was 26% (complete response [CR], n = 8; partial response [PR], n = 5), and regression of both injected and distant (including visceral) lesions occurred. Ninety-two percent of the responses had been maintained for 7 to 31 months. Ten additional patients had stable disease (SD) for greater than 3 months, and two additional patients had surgical CR. On an extension protocol, two patients subsequently achieved CR by 24 months (one previously PR, one previously SD), and one achieved surgical CR (previously PR). Overall survival was 58% at 1 year and 52% at 24 months.
  
  
  CONCLUSIONS
  The 26% response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.
authors.affiliation: Mary Crowley Cancer Research Centers, Dallas, TX 75201, USA. nsenzer@marycrowley.org
authors.forename: Neil N
authors.initials: NN
authors.lastname: Senzer
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.forename: Thomas
authors.initials: T
authors.lastname: Amatruda
authors.forename: Mike
authors.initials: M
authors.lastname: Nemunaitis
authors.forename: Tony
authors.initials: T
authors.lastname: Reid
authors.forename: Gregory
authors.initials: G
authors.lastname: Daniels
authors.forename: Rene
authors.initials: R
authors.lastname: Gonzalez
authors.forename: John
authors.initials: J
authors.lastname: Glaspy
authors.forename: Eric
authors.initials: E
authors.lastname: Whitman
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Howard
authors.initials: H
authors.lastname: Goldsweig
authors.forename: Tracey
authors.initials: T
authors.lastname: Marshall
authors.forename: Colin
authors.initials: C
authors.lastname: Love
authors.forename: Robert
authors.initials: R
authors.lastname: Coffin
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D018259:Herpesvirus 1, Human; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D012878:Skin Neoplasms / Q000473:pathology*
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor