title: Efficacy and safety of a new device for intravesical thermochemotherapy in non-grade 3 BCG recurrent NMIBC: a phase I-II study.
abstract: OBJECTIVE
  We report for the first time the activity and safety of Unithermia(®) (Elmedical Ltd, Hod-Hasharon, Israel), a novel device for administration of MMC-C with hyperthermia (HT), that employs conductive heating, in a series of non-grade 3 non-muscle-invasive bladder cancer (NMIBC) that failed Bacillus Calmette-Guerin (BCG).
  
  
  METHODS
  Patients with non-grade 3 NMIBC recurring after at least a full induction course of BCG were eligible for this phase I-II prospective single-arm study. Six weekly instillations with Unithermia(®) were scheduled following complete TUR. Primary end points were treatment safety and response rate (RR), and the latter defined as the absence of any unfavourable outcome at 12 months. Any grade 3 and/or muscle-invasive (T > 1) recurrence was considered disease progression. Kaplan-Meier estimation of the time to recurrence and progression, cancer-specific survival and overall survival was taken as secondary end points.
  
  
  RESULTS
  Thirty-four eligible patients entered the study between January 2009 and April 2011. RR was documented in 20/34 (59%). Among the 14/34 (41%) non-responders, four developed G3 disease, one developed carcinoma in situ, and one progressed to muscle-invasive bladder cancer, with an overall 18% progression rate at 1 year. At a median follow-up of 41 months, recurrence and progression rates were 35.3 and 23.5%, respectively. Toxicity did not go beyond grade 2 except in five cases.
  
  
  CONCLUSIONS
  Initial experience with MMC-HT with Unithermia(®) showed an interesting activity and safety profile in non-grade 3 NMIBC recurring after BCG, suggesting a role as second-line therapy in this selected subgroup of NMIBC.
authors.affiliation: Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, C.so Bramante 88/90, 10126, Turin, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Soria
authors.affiliation: Department of Pharmacology, University of Studies of Torino, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Milla
authors.affiliation: Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, C.so Bramante 88/90, 10126, Turin, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fiorito
authors.affiliation: Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, C.so Bramante 88/90, 10126, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pisano
authors.affiliation: Urology Clinic, Maggiore della Carità Hospital, Novara, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Sogni
authors.affiliation: Urology Unit, Casa di Cura Guarnieri, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Marco
authors.affiliation: Urology Clinic, Policlinico of Bari, Bari, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pagliarulo
authors.affiliation: Department of Pharmacology, University of Studies of Torino, Turin, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dosio
authors.affiliation: Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, C.so Bramante 88/90, 10126, Turin, Italy. paolo.gontero@unito.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000283:Administration, Intravesical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D004867:Equipment Design; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced / Q000295:instrumentation*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine
keywords: BCG failure; Bladder cancer; Device assisted; Intravesical chemotherapy; Thermochemotherapy