title: Safety and side effects of immediate instillation of apaziquone following transurethral resection in patients with nonmuscle invasive bladder cancer.
abstract: OBJECTIVE
  We studied the safety, tolerability and pharmacokinetics of a single immediate post-transurethral resection intravesical instillation of apaziquone for patients with nonmuscle invasive bladder cancer.
  
  
  METHODS
  Patients with cTa-T1, G1-G2 urothelial cell carcinoma of the bladder underwent transurethral resection of bladder tumor(s) followed by a single intravesical instillation of apaziquone 4 mg/40 ml for 1 hour within 6 hours of transurethral bladder tumor resection. Adverse events and safety parameters were assessed on days 8 and 15 after transurethral bladder tumor resection. Blood samples were drawn before and during the instillation for pharmacokinetic analyses. The first 10 patients with pTa-T1, G1-G2 nonmuscle invasive bladder cancer were also evaluated by cystoscopy 3 months after treatment to determine mucosal healing.
  
  
  RESULTS
  Of 20 patients receiving apaziquone 13 (65%) reported 35 adverse events, mostly grade 1 to 2. Eight patients (40%) reported 13 adverse events related to treatment, in particular dysuria, hematuria, bladder spasm, abdominal pain, asthenia and postoperative urinary retention. Three grade 3 and 1 grade 4 event(s) occurred, but these were considered unrelated to treatment. No other significant clinical changes were observed. Apaziquone and the active metabolite EO5a were not detected with pharmacokinetic analyses at any point of time. After 3 months no evidence of impaired mucosal healing was observed.
  
  
  CONCLUSIONS
  A single immediate post-transurethral bladder tumor resection instillation of apaziquone was well tolerated with an expected good safety profile. Apaziquone and its metabolite EO5a were not detected systemically with pharmacokinetic analyses. These results have lead to further study of a single immediate instillation of apaziquone.
authors.affiliation: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Hendricksen
authors.forename: D
authors.initials: D
authors.lastname: Gleason
authors.forename: J M
authors.initials: JM
authors.lastname: Young
authors.forename: D
authors.initials: D
authors.lastname: Saltzstein
authors.forename: A
authors.initials: A
authors.lastname: Gershman
authors.forename: S
authors.initials: S
authors.lastname: Lerner
authors.forename: J A
authors.initials: JA
authors.lastname: Witjes
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001388:Aziridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D045563:Indolequinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*
chemical_list: D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; C060817:apaziquone