title: Pharmacokinetic and toxicity considerations in the use of neoadjuvant chemotherapy for bladder cancer.
abstract: BACKGROUND
  Neoadjuvant cisplatin-based combination chemotherapy remains the standard of care for surgically fit patients with muscle-invasive bladder cancer (MIBC). However, significant practice variability exists both in the use of neoadjuvant chemotherapy (NACT) and in the utilized regimens.
  
  
  METHODS
  This review summarizes the available evidence on the pharmacokinetic, toxicology and efficacy considerations for determining appropriate neoadjuvant therapy in MIBC. This article consists of material obtained via PubMed, Medline and EMBASE literature searches up to November 2014.
  
  
  CONCLUSIONS
  The role of NACT in MIBC cancer is well established. Common barriers to the successful use of NACT are the toxicities of therapy, the presence of underlying renal dysfunction, the time delay to definitive surgery and the potential for an inadequate treatment effect. The key finding from published NACT trials is that patients who successfully attain a complete pathologic response at the time of radical cystectomy can achieve durable long-term survivals. Although recent investigations into dose-dense NACT regimens have provided intriguing results, alterations in dose intensity alone are unlikely to provide substantial clinical improvements. Further research into NACT should be directed towards the investigation of novel neoadjuvant therapies and to the evaluation of biomarkers predictive of complete pathologic response or decreased toxicities with standard cisplatin-based NACT.
authors.affiliation: Hospital of the University of Pennsylvania, Abramson Cancer Center, Division of Hematology/Oncology , 16 Penn Tower, Philadelphia, PA , USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Narayan
authors.forename: David
authors.initials: D
authors.lastname: Vaughn
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy / Q000379:methods; D006801:Humans; D020360:Neoadjuvant Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin
keywords: cisplatin; doxorubicin; gemcitabine; methotrexate; muscle-invasive bladder cancer; neoadjuvant; pharmacokinetic; toxicity; vinblastine