title: Phase II Study of Pazopanib and Paclitaxel in Patients With Refractory Urothelial Cancer.
abstract: Currently, no standard treatments are available for relapsed or refractory urothelial carcinoma (UC). Paclitaxel has demonstrated efficacy in the treatment of UC when used alone or combined with other cytotoxic therapies. We designed a phase II trial combining paclitaxel with pazopanib, a commonly used antiangiogenic agent with significant antitumor activity in various solid tumors.
  
  
  
  We enrolled 32 patients with refractory UC who had demonstrated disease progression after 2 previous chemotherapeutic regimens. The patients received paclitaxel 80 mg/m2on days 1, 8, and 15 of a 28-day cycle and oral pazopanib 800 mg daily. The primary endpoint was the overall response rate (ORR). The secondary endpoints included progression-free survival, overall survival, and a safety assessment of the combination.
  
  
  
  Of the 28 evaluable patients, a complete response was observed in 3 patients and a partial response in 12, with an ORR of 54% (95% confidence interval, 33.9-72.5). The median progression-free and overall survival was 6.2 and 10 months, respectively. The most frequent side effects noted (all grades) were fatigue (63%), diarrhea (44%), and nausea and vomiting (41%). Hematologic toxicities were common and included (all grades) anemia (69%), neutropenia (38%), and thrombocytopenia (47%). Growth factor support was required for 44% of the patients.
  
  
  
  The combination of paclitaxel and pazopanib resulted in a promising ORR of 54% in patients with advanced pretreated UC. This represents a greater response rate and median survival than found with other existing second-line regimens for UC and is worthy of further study.
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Narayanan
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lam
authors.affiliation: Karmanos Cancer Institute, Detroit, MI.
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Harshman
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Alice
authors.initials: A
authors.lastname: Fan
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Russell
authors.initials: R
authors.lastname: Pachynski
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Shermeen
authors.initials: S
authors.lastname: Poushnejad
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Denise
authors.initials: D
authors.lastname: Haas
authors.affiliation: Stanford Cancer Center, Stanford, CA.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Stanford Cancer Center, Stanford, CA. Electronic address: sandysri@stanford.edu.
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy*
chemical_list: D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D017239:Paclitaxel
keywords: Angiogenesis inhibitor; Chemotherapy; Combination; Second line; Targeted therapy