title: Phase 2 trial of combination thalidomide plus temozolomide in patients with metastatic malignant melanoma: Southwest Oncology Group S0508.
abstract: BACKGROUND
  In limited institution phase 2 studies, thalidomide and temozolomide has yielded response rates (RRs) up to 32% for advanced melanoma, leading to the use of this combination as "standard" by some. We conducted a multicenter phase 2 trial to better define the clinical efficacy of thalidomide and temozolomide and the immune modulatory effects of thalidomide, when combined with temozolomide, in patients with metastatic melanoma.
  
  
  METHODS
  Patients must have had stage IV cutaneous melanoma, no active brain metastases, Zubrod PS 0-1, up to 1 prior systemic therapy excluding thalidomide, temozolomide, or dacarbazine, adequate organ function, and given informed consent. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included overall survival (OS), RR, toxicities, and assessment of relationships between biomarkers and clinical outcomes. Patients received thalidomide (200 mg/d escalated to 400 mg/d for patients <70, or 100 mg/d escalated to 250 mg/d for patients > or =70) plus temozolomide (75 mg/m(2)/d x 6 weeks, and then 2 weeks rest).
  
  
  RESULTS
  Sixty-four patients were enrolled; 2 refused treatment. The 6-month PFS was 15% (95% confidence interval [CI], 6%-23%), the 1-year OS was 35% (95% CI, 24%-47%), and the RR was 13% (95% CI, 5%-25%), all partial. One treatment-related death occurred from myocardial infarction; 3 other grade 4 events occurred, including pulmonary embolism, neutropenia, and central nervous system (CNS) ischemia. There was no significant correlation between biomarkers and PFS or OS.
  
  
  CONCLUSIONS
  This combination of thalidomide and temozolomide does not appear to have a clinical benefit that exceeds dacarbazine alone. We would not recommend it further for phase 3 trials or for standard community use.
authors.affiliation: Cardinal Bernardin Cancer Center, Loyola University Medical Center, Division of Hematology/Oncology, 2160 South First Avenue, Maywood, IL 60153, USA. jclark@lumc.edu
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Laura F
authors.initials: LF
authors.lastname: Hutchins
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
authors.forename: Diane M
authors.initials: DM
authors.lastname: Da Silva
authors.forename: P Y
authors.initials: PY
authors.lastname: Liu
authors.forename: John A
authors.initials: JA
authors.lastname: Thompson
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Flaherty
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D000077204:Temozolomide; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D013792:Thalidomide; D003606:Dacarbazine; D000077204:Temozolomide