title: Melphalan 180 mg/m2 can be safely administered as conditioning regimen before an autologous stem cell transplantation (ASCT) in multiple myeloma patients with creatinine clearance 60 mL/min/1.73 m2 or lower with use of palifermin for cytoprotection: results of a phase I trial.
abstract: High-dose melphalan 140 mg/m2 is the standard of care for patients with multiple myeloma (MM) with renal insufficiency (RI). Palifermin as a cytoprotective agent has demonstrated efficacy in reducing the intensity and duration of oral mucositis (OM) in patients who receive intensive chemotherapy/radiotherapy. There is no prospective data on the use of palifermin in patients with MM with RI.
  
  
  METHODS
  creatinine clearance ≤60 mL/minute/1.73 m2, age >18 years, no dialysis, no active OM, and a suitable candidate for autologous stem cell transplant (ASCT). Melphalan dose ranged from 140 to 200 mg/m2 and escalated at the increment of 20 mg/m2. Six dosages of palifermin 60 mcg/kg/day were given intravenously between day -5 to day +3. Dose escalations were to stop if dose-limiting toxicities (DLTs) occurred at melphalan dose in ≥2 of 3 patients, with that dose declared as the maximal administered dose and the level below where ≤1 of 6 patients had DLTs was considered the maximally tolerated dose (MTD). Nineteen patients were enrolled from June 2007 to June 2011. Data on 15 evaluable patients is reported as 4 patients were removed. Median age was 59 years (range, 36-67 years). The overall incidence of OM ≥ grade 3 was 53% (8 of 15) and a median duration of ≥grade 3 OM was 6.5 days (range, 3-42 days). One patient in L2 (melphalan 160 mg/m2) developed atrial fibrillation on day +9. Two patients in L4 (melphalan 200 mg/m2) developed grade 4 OM, hence reaching DLT. No DLT was observed in 6 patients enrolled in L3 (melphalan 180 mg/m2). Palifermin has permitted safe dose escalation of melphalan up to 180 mg/m(2) in patients with RI.
authors.affiliation: Karmanos Cancer Institute, Detroit, Michigan 48201, USA. abidim@karmanos.org
authors.forename: Muneer H
authors.initials: MH
authors.lastname: Abidi
authors.forename: Rishi
authors.initials: R
authors.lastname: Agarwal
authors.forename: Lois
authors.initials: L
authors.lastname: Ayash
authors.forename: Abhinav
authors.initials: A
authors.lastname: Deol
authors.forename: Zaid
authors.initials: Z
authors.lastname: Al-Kadhimi
authors.forename: Judith
authors.initials: J
authors.lastname: Abrams
authors.forename: Simon
authors.initials: S
authors.lastname: Cronin
authors.forename: Marie
authors.initials: M
authors.lastname: Ventimiglia
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lum
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Zonder
authors.forename: Voravit
authors.initials: V
authors.lastname: Ratanatharathorn
authors.forename: Joseph
authors.initials: J
authors.lastname: Uberti
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000276:immunology / Q000628:therapy*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000276:immunology / Q000628:therapy*; D013280:Stomatitis / Q000150:complications / Q000276:immunology / Q000628:therapy; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D051523:Fibroblast Growth Factor 7; D003404:Creatinine; D008558:Melphalan