title: Early response predicts thalidomide efficiency in patients with advanced multiple myeloma.
abstract: Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0.200/h, 0.140/h, 0.886 l/kg, 0.126 l/h/kg and 4.98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks.
authors.affiliation: Department of Haematology, University Hospital Trondheim, N-7006 Trondheim, Norway. anders.waage@medisin.ntnu.no
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.forename: Peter
authors.initials: P
authors.lastname: Gimsing
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Nina
authors.initials: N
authors.lastname: Gulbrandsen
authors.forename: Tommy
authors.initials: T
authors.lastname: Eriksson
authors.forename: Martin
authors.initials: M
authors.lastname: Hjorth
authors.forename: Johan Lanng
authors.initials: JL
authors.lastname: Nielsen
authors.forename: Stig
authors.initials: S
authors.lastname: Lenhoff
authors.forename: Jan
authors.initials: J
authors.lastname: Westin
authors.forename: Finn
authors.initials: F
authors.lastname: Wislöff
mesh_terms: D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011788:Quality of Life; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001798:Blood Proteins; D006454:Hemoglobins; D007136:Immunoglobulins; C009823:M-proteins (Myeloma); D013792:Thalidomide