title: Amifostine pretreatment for protection against topotecan-induced hematologic toxicity: results of a multicenter phase III trial in patients with advanced gynecologic malignancies.
abstract: OBJECTIVE
  To determine if amifostine could reduce the hematologic toxicity associated with topotecan.
  
  
  METHODS
  Thirty patients with recurrent/refractory gynecologic malignancies were randomized to receive topotecan (TOPO) (1.5 mg/m(2)/day days 1-5) with or without amifostine (AMI/TOPO) (500 mg/m(2)/day days 1-5) every 3 weeks for six cycles. The primary study endpoints were the incidence of grade 3 and 4 neutropenia.
  
  
  RESULTS
  Fifteen patients were randomized to each arm for a total of 49 TOPO and 53 AMI/TOPO cycles. Patient characteristics and pretreatment ANC were similar between groups. Topotecan 1.5 mg/m(2)/day days 1-5 was initially administered to seven patients. Five developed neutropenic fevers, one an uncomplicated grade 4 neutropenia, and the other an uncomplicated grade 3 neutropenia. There were two treatment-related deaths due to sepsis (one in each treatment arm). The starting dose was thereafter reduced to 1.25 mg/m(2)/day days 1-5 every 21 days. No treatment related deaths occurred after this dose reduction. The incidence of combined grade 3/4 neutropenia was reduced from 67% (33/49 cycles) to 38% (20/53 cycles) with the addition of amifostine (P = 0.003; OR 0.29; 95% CI 0.12-0.71).
  
  
  CONCLUSIONS
  Topotecan at 1.5 mg/m(2)/day days 1-5 in heavily pretreated patients resulted in excessive toxicity not manageable with amifostine. At the reduced topotecan dose (1.25 mg/m(2) x 5 days), pretreatment with amifostine reduced the hematologic toxicity associated with topotecan chemotherapy in women with recurrent/refractory gynecologic malignancies.
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. michael-gold@ouhsc.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Berek
authors.forename: Alton V
authors.initials: AV
authors.lastname: Hallum
authors.forename: Dava J
authors.initials: DJ
authors.lastname: Garcia
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
mesh_terms: D000328:Adult; D000368:Aged; D004999:Amifostine / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D019772:Topotecan / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D004999:Amifostine