PMID- 22575238
OWN - NLM
STAT- MEDLINE
DCOM- 20140804
LR  - 20220330
IS  - 1873-2496 (Electronic)
IS  - 1078-1439 (Linking)
VI  - 31
IP  - 8
DP  - 2013 Nov
TI  - Intravesical valrubicin in patients with bladder carcinoma in situ and 
      contraindication to or failure after bacillus Calmette-Guerin.
PG  - 1635-42
LID - S1078-1439(12)00151-2 [pii]
LID - 10.1016/j.urolonc.2012.04.010 [doi]
AB  - OBJECTIVES: Evaluate the efficacy and safety of valrubicin for bacillus 
      Calmette-Guerin (BCG)-refractory carcinoma in situ (CIS) of the bladder based on 
      updated phase III pivotal trial efficacy data together with efficacy and safety 
      data from a supportive phase II/III study. MATERIALS AND METHODS: In a phase 
      II/III open-label study (A9303), BCG refractory/intolerant adults with CIS (>/= 1 
      previous course of BCG or could not complete a BCG course owing to toxicity or 
      contraindication) were randomized to receive 6 or 9 weekly intravesical 
      valrubicin (800 mg) instillations. In the pivotal phase III open-label study, 
      BCG-refractory/recurrent adults with CIS (>/= 2 previous courses of intravesical 
      therapy, including >/= 1 BCG course) received 6 weekly intravesical valrubicin (800 
      mg) instillations. Patients with muscle-invasive disease were excluded. Patients 
      underwent a primary disease evaluation (PDE) at 3 months ( approximately  6 weeks after last 
      dose) that included cytoscopy, biopsy, and cytology. Disease recurrence was 
      monitored at 3-month intervals. Complete response (CR) was defined as no evidence 
      of disease at the PDE (month 3) and follow-up (month 6). Efficacy data from the 
      pivotal trial reflect updated information based on US Food and Drug 
      Administration review. Safety assessments in A9303 included local bladder adverse 
      events (LBAEs) and other adverse events (AEs). RESULTS: Eighty patients enrolled 
      and 78 completed treatment and underwent the PDE in study A9303; in the pivotal 
      trial, the respective numbers were 90 and 87 patients. In study A9303, 39% of 
      patients had received >/= 2 previous courses of BCG and 11% had received >/= 3 
      courses vs. 70% and 28%, respectively, in the pivotal trial. In both studies, the 
      CR rate was 18%. In A9303, LBAEs were the most common AEs, reported by 86% of 
      patients during treatment and 45% during follow-up; most treatment-related LBAEs 
      were mild to moderate. 2 serious AEs in 1 patient (azotemia/reflux nephropathy) 
      were judged as definitely or possibly treatment related; none of the patient 
      deaths were judged to be related to valrubicin. CONCLUSIONS: Two trials of 
      valrubicin in patients with CIS demonstrate a consistent degree of efficacy in 
      highly pretreated patients (pivotal trial; BCG-refractory patients) and those 
      with fewer previous therapies (A9303; BCG-refractory/intolerant patients).
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Dinney, Colin P N
AU  - Dinney CP
AD  - University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. 
      Electronic address: cdinney@mdanderson.org.
FAU - Greenberg, Richard E
AU  - Greenberg RE
FAU - Steinberg, Gary D
AU  - Steinberg GD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120509
PL  - United States
TA  - Urol Oncol
JT  - Urologic oncology
JID - 9805460
RN  - 0 (BCG Vaccine)
RN  - 2C6NUM6878 (valrubicin)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Abdominal Pain/chemically induced
MH  - Administration, Intravesical
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - BCG Vaccine/*therapeutic use
MH  - Carcinoma in Situ/*drug therapy
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Contraindications
MH  - Doxorubicin/adverse effects/*analogs & derivatives/therapeutic use
MH  - Dysuria/chemically induced
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Middle Aged
MH  - Outcome Assessment, Health Care/methods
MH  - Randomized Controlled Trials as Topic
MH  - Treatment Failure
MH  - Urinary Bladder Neoplasms/*drug therapy
MH  - Urinary Tract Infections/chemically induced
OTO - NOTNLM
OT  - Bladder tumor
OT  - Carcinoma in situ
OT  - Intravesical Chemotherapy
OT  - Non-muscle-invasive bladder cancer
OT  - bacillus Calmette-Guerin
OT  - valrubicin
EDAT- 2012/05/12 06:00
MHDA- 2014/08/05 06:00
CRDT- 2012/05/12 06:00
PHST- 2012/02/03 00:00 [received]
PHST- 2012/04/10 00:00 [revised]
PHST- 2012/04/10 00:00 [accepted]
PHST- 2012/05/12 06:00 [entrez]
PHST- 2012/05/12 06:00 [pubmed]
PHST- 2014/08/05 06:00 [medline]
AID - S1078-1439(12)00151-2 [pii]
AID - 10.1016/j.urolonc.2012.04.010 [doi]
PST - ppublish
SO  - Urol Oncol. 2013 Nov;31(8):1635-42. doi: 10.1016/j.urolonc.2012.04.010. Epub 2012 
      May 9.