title: Phase II trial of cetuximab with or without paclitaxel in patients with advanced urothelial tract carcinoma.
abstract: OBJECTIVE
  The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer.
  
  
  METHODS
  Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m(2) with or without paclitaxel 80 mg/m(2) per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks.
  
  
  RESULTS
  We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases).
  
  
  CONCLUSIONS
  Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Wong
authors.forename: Samuel
authors.initials: S
authors.lastname: Litwin
authors.forename: David
authors.initials: D
authors.lastname: Vaughn
authors.forename: Seth
authors.initials: S
authors.lastname: Cohen
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Plimack
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Michael
authors.initials: M
authors.lastname: Dabrow
authors.forename: Marion
authors.initials: M
authors.lastname: Brody
authors.forename: Holly
authors.initials: H
authors.lastname: Tuttle
authors.forename: Gary
authors.initials: G
authors.lastname: Hudes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy; D000068818:Cetuximab; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D017239:Paclitaxel; D000068818:Cetuximab