title: Phase II trial of neoadjuvant temozolomide in resectable melanoma patients.
abstract: BACKGROUND
  We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing.
  
  
  METHODS
  Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles.
  
  
  RESULTS
  Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients.
  
  
  CONCLUSIONS
  The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.
authors.affiliation: Department of Medicine.
authors.forename: G D
authors.initials: GD
authors.lastname: Shah
authors.affiliation: Department of The Computational Biology Center.
authors.forename: N D
authors.initials: ND
authors.lastname: Socci
authors.affiliation: Department of Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Gold
authors.affiliation: Department of Medicine.
authors.forename: J D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: Department of Medicine.
authors.forename: R D
authors.initials: RD
authors.lastname: Carvajal
authors.affiliation: Department of Epidemiology and Biostatistics.
authors.forename: K S
authors.initials: KS
authors.lastname: Panageas
authors.affiliation: Department of The Genomics Core Laboratory.
authors.forename: A
authors.initials: A
authors.lastname: Viale
authors.affiliation: Department of Surgery.
authors.forename: M S
authors.initials: MS
authors.lastname: Brady
authors.affiliation: Department of Surgery.
authors.forename: D G
authors.initials: DG
authors.lastname: Coit
authors.affiliation: Department of Medicine. Electronic address: chapmanp@mskcc.org.
authors.forename: P B
authors.initials: PB
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide