title: Phase II study of gemcitabine, carboplatin, and bevacizumab in patients with advanced unresectable or metastatic urothelial cancer.
abstract: OBJECTIVE
  Although gemcitabine and carboplatin (GCa) is a standard option for patients with advanced urothelial cancer (UC) who are ineligible for cisplatin, outcomes remain poor. This trial evaluated the efficacy and safety of bevacizumab with GCa in advanced UC.
  
  
  METHODS
  Patients with Karnofsky performance status of 60% to 70%, creatinine clearance less than 60 mL/min, visceral metastasis, or solitary kidney were eligible and received a lead-in dose of bevacizumab 10 mg/kg followed 2 weeks later by gemcitabine 1,000 mg/m(2) on days 1 and 8 and carboplatin at area under the [concentration-time] curve (AUC) 5.0 or 4.5 and bevacizumab 15 mg/kg on day 1 every 21 days for six cycles. Patients achieving at least stable disease (SD) continued bevacizumab 15 mg/kg every 21 days for 18 additional cycles. The study was powered to detect a 50% improvement in median progression-free survival (PFS) over a historical control.
  
  
  RESULTS
  Fifty-one patients, median age 67 years (range, 42 to 83 years), were enrolled onto the study and were evaluable for toxicity. Twenty (39%) experienced grade 3 to 4 toxicity, and 10 (20%) had thromboembolic events (deep venous thrombosis or pulmonary embolism). Four received one or fewer cycles leaving 47 evaluable for outcomes. Twenty-three (49%) achieved response (three complete; 20 partial), and 11 had SD. Median PFS was 6.5 months (95% CI, 4.7 to 7.8 months); PFS was greater in the carboplatin AUC 5.0 group (P = .04). Median overall survival (OS) was 13.9 months.
  
  
  CONCLUSIONS
  The 95% one-sided lower confidence bound of 4.77 months for median PFS did not meet the predesignated PFS of more than 4.8 months considered sufficient for further study. Median OS was greater than expected. An ongoing phase III trial in patients who are eligible for therapy with cisplatin will define the role of bevacizumab in UC.
authors: Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: Arjun V
authors: AV
authors: Balar
authors: Andrea B
authors: AB
authors: Apolo
authors: Irina
authors: I
authors: Ostrovnaya
authors: Svetlana
authors: S
authors: Mironov
authors: Alexia
authors: A
authors: Iasonos
authors: Alisa
authors: A
authors: Trout
authors: Ashley M
authors: AM
authors: Regazzi
authors: Ilana R
authors: IR
authors: Garcia-Grossman
authors: David J
authors: DJ
authors: Gallagher
authors: Matthew I
authors: MI
authors: Milowsky
authors: Dean F
authors: DF
authors: Bajorin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003248:Constipation / Q000139:chemically induced; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D016190:Carboplatin; D000093542:Gemcitabine