title: Temozolomide, thalidomide, and whole brain radiation therapy for patients with brain metastasis from metastatic melanoma: a phase II Cytokine Working Group study.
abstract: BACKGROUND
  The combination of temozolomide (TMZ) and thalidomide was reported to produce a high response rate, including shrinkage of brain metastases, in patients with metastatic melanoma. The authors tested the efficacy of a regimen including TMZ, thalidomide, and whole brain radiation therapy (WBRT) in patients with brain (CNS) metastases from melanoma.
  
  
  METHODS
  Patients with melanoma, CNS metastases documented by magnetic resonance imaging, and no prior systemic chemotherapy received WBRT, 30 Gray in 10 fractions, Days 1 to 5 and 8 to 12; TMZ, 75 mg/m(2)/day, Weeks 1 to 6; and thalidomide, 100 mg/day, Weeks 1 to 4, then escalated by 100 mg/day at Weeks 5, 7, and 9 as tolerated to a maximum of 400 mg/day. CNS and systemic tumor response was assessed at Week 10. Patients without CNS or clinically significant systemic disease progression received additional cycles of TMZ at 10-week intervals.
  
  
  RESULTS
  Thirty-nine patients received treatment, and 3 exhibited CNS response (1 complete response, 2 partial responses) (response rate, 7.6%; 95% confidence interval, 0.7%-16.1%), all unconfirmed by repeat imaging. Seven patients had stable CNS disease at 10 weeks. No patient exhibited a systemic response. Only 4 patients received 2 cycles of therapy, and just 1 received 3. Median time to progression was 7 weeks, and median overall survival was 4 months. Grade 3-4 side effects included deep venous thrombosis (3), pulmonary embolism (1), and CNS events (12). Eighteen (45%) patients required admission for side effects (7) and/or symptomatic disease progression (11).
  
  
  CONCLUSIONS
  The efficacy of TMZ, thalidomide, and WBRT in the treatment of CNS metastatic melanoma is low. Other treatment approaches should be considered for this patient population.
authors.affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. Matkins@bidmc.harvard.edu
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Agarwala
authors.forename: Theodore
authors.initials: T
authors.lastname: Logan
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: Marc S
authors.initials: MS
authors.lastname: Ernstoff
authors.forename: David
authors.initials: D
authors.lastname: Lawson
authors.forename: Janice P
authors.initials: JP
authors.lastname: Dutcher
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Weiss
authors.forename: Brendan
authors.initials: B
authors.lastname: Curti
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D000077204:Temozolomide; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D013792:Thalidomide; D003606:Dacarbazine; D000077204:Temozolomide