title: Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study.
abstract: BACKGROUND
  No standard treatment exists for patients with platinum-refractory urothelial cancer. Taxanes and vinflunine are commonly used, but response is less than 20% with no survival benefit. In this phase 2 study, we assessed efficacy and tolerability of nanoparticle albumin-bound (nab) paclitaxel in platinum-refractory urothelial cancer.
  
  
  METHODS
  We did an open-label, single-group, two-stage study at five centres in Canada. We enrolled patients aged at least 18 years with histologically confirmed, locally advanced, or metastatic measurable urothelial cancer, with documented progression on or within 12 months of treatment with one previous platinum-containing regimen. Patients received nab-paclitaxel at 260 mg/m(2) intravenously every 3 weeks. Treatment continued until disease progression or occurrence of unacceptable toxic effects. The primary endpoint was objective tumour response, defined by a complete response (CR) or partial response (PR) according to Response Evaluation Criteria In Solid Tumors (version 1.0) criteria. Tumour response and safety were assessed in all patients who received at least one cycle of nab-paclitaxel. This study is registered with ClinicalTrials.gov, number NCT00683059.
  
  
  RESULTS
  We enrolled 48 patients between Oct 16, 2008, and June 23, 2010. Patients received a median of six cycles (range one to 15). 47 patients were evaluable; one (2·1%) had a CR and 12 (25·5%) had PRs, resulting in an overall response of 27·7% (95% CI 17·3-44·4). The most frequently recorded adverse events of any grade were fatigue (38 of 48; 79%), pain (37 of 48; 77%), alopecia (34 of 48; 71%), and neuropathy (30 of 48; 77%). The most frequently recorded adverse events of grade 3 or higher were pain (11 of 48; 23%), fatigue (five of 48; 23%), hypertension (three of 48; 6%), neuropathy (three of 48, 6%), and joint stiffness or pain (two of 48; 4%).
  
  
  CONCLUSIONS
  Nab-paclitaxel was well tolerated in this population of patients with pretreated advanced urothelial cancer with an encouraging tumour response. These results warrant further study of nab-paclitaxel in second-line treatment of urothelial cancer.
  
  
  BACKGROUND
  Abraxis Bioscience, Celgene.
authors.affiliation: Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
authors.forename: Yoo-Joung
authors.initials: YJ
authors.lastname: Ko
authors.forename: Christine M
authors.initials: CM
authors.lastname: Canil
authors.forename: Som D
authors.initials: SD
authors.lastname: Mukherjee
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Christine
authors.initials: C
authors.lastname: Elser
authors.forename: Andrea
authors.initials: A
authors.lastname: Eisen
authors.forename: M Neil
authors.initials: MN
authors.lastname: Reaume
authors.forename: Liying
authors.initials: L
authors.lastname: Zhang
authors.forename: Srikala S
authors.initials: SS
authors.lastname: Sridhar
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D002170:Canada; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D002626:Chemistry, Pharmaceutical; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome; D014516:Ureteral Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D017239:Paclitaxel