title: A phase II trial of neoadjuvant nab-paclitaxel, carboplatin, and gemcitabine (ACaG) in patients with locally advanced carcinoma of the bladder.
abstract: OBJECTIVE
  To assess the activity of neoadjuvant nab-paclitaxel, carboplatin, gemcitabine (ACaG) followed by cystectomy in patients with muscle-invasive urothelial carcinoma of the bladder.
  
  
  METHODS
  Patients who were candidates for cystectomy received nab-paclitaxel 260 mg/m(2) on day 1, carboplatin area under the curve 5 on day 1, and gemcitabine 800 mg/m(2) on days 1 and 8, every 21 days for 3 cycles. The first 3 patients received nab-paclitaxel 100 mg/m(2) weekly and were not included in the efficacy analysis of evaluable patients. Efficacy was assessed by the percentage of patients with pathologic complete response (pT0) at cystectomy. Progression-free and overall survival was estimated using the Kaplan-Meier methods.
  
  
  RESULTS
  Of 29 patients enrolled, 26 received the planned 3 cycles with 82 cycles overall; doses were reduced in 16 patients. Of 29 patients, nearly all patients experienced grade 3-4 neutropenia; 17 patients (58.6%) required growth factor, and 16 patients (55.2%) experienced grade 3-4 thrombocytopenia; there was 1 toxicity-related death. Nonhematological toxicity was generally tolerable. Twenty-two of 26 patients were evaluable for the primary endpoint: 6 patients (27.3%, 95% confidence interval [CI] 10.7-50.2) had pT0, 6 pTis, 1 pT1, 54.5% of patients had no residual muscle-invasive disease (<pT2N0), and 81.8% had pN0 at cystectomy. By intent-to-treat (ITT) analysis, the pT0 rate was 27.6% (95% CI 12.7-47.2).
  
  
  CONCLUSIONS
  Neoadjuvant nab-paclitaxel, carboplatin, gemcitabine is feasible but grade 3-4 myelotoxicity is common. Although the regimen has activity, the pT0 rate is lower than those reported with cisplatin-based regimens and did not meet the predefined threshold to support further investigation. Taxane-based regimens remain investigational for neoadjuvant therapy of bladder cancer.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Petros D
authors.initials: PD
authors.lastname: Grivas
authors.forename: Maha
authors.initials: M
authors.lastname: Hussain
authors.forename: Khaled
authors.initials: K
authors.lastname: Hafez
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault-Newton
authors.forename: David
authors.initials: D
authors.lastname: Wood
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.forename: Alon
authors.initials: A
authors.lastname: Weizer
authors.forename: James E
authors.initials: JE
authors.lastname: Montie
authors.forename: Brent
authors.initials: B
authors.lastname: Hollenbeck
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Montgomery
authors.forename: Ajjai
authors.initials: A
authors.lastname: Alva
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine