title: Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma.
abstract: BACKGROUND
  The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study.
  
  
  METHODS
  A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m(2)), or DTIC (850 mg/m(2)) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle.
  
  
  RESULTS
  The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia.
  
  
  CONCLUSIONS
  PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study.
authors.affiliation: Department of Oncologic Sciences, Moffitt Cancer Center, Tampa, FL, USA. Jeffrey.Weber@moffitt.org
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Hassan
authors.initials: H
authors.lastname: Zarour
authors.forename: Bruce
authors.initials: B
authors.lastname: Redman
authors.forename: Uwe
authors.initials: U
authors.lastname: Trefzer
authors.forename: Steven
authors.initials: S
authors.lastname: O'Day
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Ernest
authors.initials: E
authors.lastname: Marshall
authors.forename: Stefan
authors.initials: S
authors.lastname: Wagner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis; D003606:Dacarbazine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D003606:Dacarbazine