title: Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF: planned interim analysis.
abstract: OBJECTIVE
  The aim of this study was to investigate the feasibility, safety, and clinical efficacy of patient-specific dendritic cell vaccines in patients with metastatic melanoma. A planned interim analysis was conducted on the first 20 patients.
  
  
  METHODS
  Tumor cell lines were established from metastatic tumor, expanded to 200 million cells, and then incubated with interferon-gamma for patients who were candidates for therapy. Cells were irradiated and cryopreserved. Patients underwent leukapheresis to obtain mononuclear cells that were cultured in the presence of IL-4 and GM-CSF to produce dendritic cells, which were incubated with cryopreserved, irradiated tumor cells, and then stored in aliquots of about 20 million cells for subcutaneous (s.c.) injections with GM-CSF once a week for 3 weeks, then once a month for 5 months.
  
  
  RESULTS
  The first 20 eligible patients included 10 men and 10 women, with a median age of 48 years (range, 16-79 years). Three (3) patients had brain metastases, and 13 patients had experienced disease progression after biochemotherapy. At the time of vaccine treatment, 6 patients had evaluable metastatic disease, while 14 patients lacked measurable disease. Vaccine therapy was well tolerated, except for what appeared to be GM-CSF-related allergic reactions in 2 patients. Delayed-type hypersensitivity (DTH) tests to irradiated tumor cells were positive in 0 of 20 patients tested at baseline, but converted to positive in 8 patients (40%). At a median follow-up of 13.8 months, there is a 95% overall survival and a 48% progression-free survival. Four (4) patients have already survived more than 3.0 years since starting the vaccine.
  
  
  CONCLUSIONS
  Based on tolerability, rate of tumor DTH conversion, and encouraging survival, the trial will continue accrual to at least 19 patients with measurable disease and 40 patients who lack measurable disease at the time of treatment.
authors.affiliation: Hoag Cancer Center, Newport Beach, CA 92658, USA. rdillman@hoaghospital.org
authors.forename: Robert
authors.initials: R
authors.lastname: Dillman
authors.forename: Senthamil
authors.initials: S
authors.lastname: Selvan
authors.forename: Patric
authors.initials: P
authors.lastname: Schiltz
authors.forename: Cheryl
authors.initials: C
authors.lastname: Peterson
authors.forename: Kanoe
authors.initials: K
authors.lastname: Allen
authors.forename: Carol
authors.initials: C
authors.lastname: Depriest
authors.forename: Edward
authors.initials: E
authors.lastname: McClay
authors.forename: Neil
authors.initials: N
authors.lastname: Barth
authors.forename: Patric
authors.initials: P
authors.lastname: Sheehy
authors.forename: Cristina
authors.initials: C
authors.lastname: de Leon
authors.forename: Linda
authors.initials: L
authors.lastname: Beutel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D015925:Cryopreservation; D003713:Dendritic Cells / Q000166:cytology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism* / Q000494:pharmacology; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D018809:Proliferating Cell Nuclear Antigen; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor