title: Novel therapy with 2-methoxyestradiol for the treatment of relapsed and plateau phase multiple myeloma.
abstract: OBJECTIVE
  2-Methoxyestradiol (2ME2) is an endogenous product of estradiol metabolism with antiangiogenic and antineoplastic properties. We report on the first phase II trial of 2ME2 in multiple myeloma.
  
  
  METHODS
  2ME2 was administered orally at a dose of 1,000 mg daily. Sixty patients (31 men and 29 women) were treated. After 39 patients were accrued, the dose was increased to 800 mg twice daily for the remaining patients.
  
  
  RESULTS
  Thirty-one patients had relapsed or refractory multiple myeloma, and 29 had plateau phase multiple myeloma. Median age was 60 years (range, 27-84 years). Therapy was well tolerated. Common adverse events included anemia (35%), fatigue (35%), nausea (25%), diarrhea (20%), hot flushes (20%), headache (17%), muscle cramps (15%), and upper respiratory tract infection (15%). Most adverse events were mild (grade 1-2); 12% experienced grade 3-4 adverse events. Median time to progression was 3.8 months, with 5.6 months for plateau phase disease and 2.3 months for relapsed multiple myeloma. Estimated progression-free survival rates for all patients at 1, 2, and 3 years were 24%, 17%, and 11%, respectively. Three patients, all with plateau phase disease, have been on study for over 4 years without progression at 50, 60, and 63 months, respectively. Minor response was noted in 2 patients.
  
  
  CONCLUSIONS
  Although no partial responses have been seen thus far, the minor responses and prolonged stable disease seen with 2ME2 therapy are promising. Plasma levels indicate that the dose of 2ME2 was inadequate. A new formulation with better bioavailability will be tested soon in multiple myeloma.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA. rajks@mayo.edu
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Robert
authors.initials: R
authors.lastname: Schlossman
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Sidor
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000077584:2-Methoxyestradiol; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D018450:Disease Progression; D018572:Disease-Free Survival; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol