title: Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients.
abstract: BACKGROUND
  Patients with relapsing or refractory multiple myeloma have poor prognosis. Few compounds are active in these patients and response duration remains short. We report the results of an open phase II trial evaluating the efficacy and safety of fotemustine monotherapy.
  
  
  METHODS
  Twenty-one patients with relapsing (17) or refractory (four) multiple myeloma received fotemustine 100 mg/m(2) on an outpatient basis on days 1 and 8 of the induction cycle, followed after a 6-week rest period by fotemustine 100 mg/m(2) every 3 weeks until progression or unacceptable toxicity. Fotemustine pharmacokinetics during the first day of induction was compared between patients with normal or abnormal renal function.
  
  
  RESULTS
  Five of 20 eligible patients had an objective response giving an intention-to-treat response rate of 25% [95% confidence interval (CI) 6% to 44%] and a 35.7% response rate (95% CI 11% to 61%) in the 14 patients having received at least four injections of fotemustine. The median time to objective response was 8.9 months. The median times to progression and survival were 13.8 and 23.1 months, respectively, with a 2-year survival rate of 49%. The main toxicity was myelosuppression with grade 3-4 neutropenia and thrombocytopenia in 66% and 71% of patients, respectively. There was one toxic death by sepsis after induction. The pharmacokinetic parameters in renal-impaired patients were not significantly different from those in patients with normal renal function with a similar incidence of grade 3-4 toxicity in both groups.
  
  
  CONCLUSIONS
  Fotemustine as a single agent has definite activity in patients with relapsing or refractory multiple myeloma, with acceptable toxicity and can be administered at conventional doses in patients with mild or moderate renal impairment.
authors.affiliation: Service d'Hématologie, CHU de Pierre Bénite, Lyon, France. charles.dumontet@chu-lyon.fr
authors.forename: C
authors.initials: C
authors.lastname: Dumontet
authors.forename: J
authors.initials: J
authors.lastname: Jaubert
authors.forename: C
authors.initials: C
authors.lastname: Sebban
authors.forename: F
authors.initials: F
authors.lastname: Bouafia
authors.forename: C
authors.initials: C
authors.lastname: Ardiet
authors.forename: B
authors.initials: B
authors.lastname: Tranchand
authors.forename: E
authors.initials: E
authors.lastname: Berger
authors.forename: C
authors.initials: C
authors.lastname: Lucas
authors.forename: D
authors.initials: D
authors.lastname: Guyotat
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010045:Outpatients; D011379:Prognosis; D012008:Recurrence; D018805:Sepsis / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; C054368:fotemustine