title: A multicenter phase II randomized study of Cremophor-free polymeric nanoparticle formulation of paclitaxel in women with locally advanced and/or metastatic breast cancer after failure of anthracycline.
abstract: OBJECTIVE
  Paclitaxel is extensively used in the treatment of advanced carcinomas of the breast, ovary and non-small cell lung cancer. In clinical use it is formulated in the non-ionic surfactant polyethoxylated castor oil (Cremophor) and dehydrated alcohol to enhance drug solubility. Cremophor adds to toxic effects of paclitaxel by producing or contributing to the well-described hypersensitivity reactions that commonly occur during its infusion, affecting a large number of patients. This randomized trial was conducted to evaluate efficacy and safety of novel nanoparticle-based paclitaxel in the treatment of patients with advanced breast cancer.
  
  
  METHODS
  Patients were randomized to receive either nanoparticle paclitaxel (NP) 300 mg/m(2) , (NP300) or NP220 mg/m(2) or Cremophor paclitaxel 175 mg/m(2) (CP 175). NP was administered as a 1-h infusion without premedication and CP as a 3-h infusion with premedication every 3 weeks.
  
  
  RESULTS
  In total, 194 patients who had been administered at least one dose were included for safety analysis and 170 patients who completed at least two cycles of therapy were analyzed for efficacy. NP showed an overall response rate (complete response + partial response) of 40% in the NP220 and NP300 arms as compared to 31% in the CP arm. The incidence of neutropenia (all grades) was lowest in the NP220 arm (39.4%) compared to the NP300 (55%) and CP arm (50%).
  
  
  CONCLUSIONS
  NP is well tolerated and can be safely administered without any premedication in comparison to conventional paclitaxel, which requires the use of premedication before administration. NP demonstrates promising efficacy with a favorable safety profile.
authors.affiliation: Deenanath Mangeshkar Hospital and Research Centre, Pune, India. draaranade@yahoo.com
authors.forename: Anantbhushan A
authors.initials: AA
authors.lastname: Ranade
authors.forename: Poonamalle P
authors.initials: PP
authors.lastname: Bapsy
authors.forename: Shona
authors.initials: S
authors.lastname: Nag
authors.forename: Digumarti
authors.initials: D
authors.lastname: Raghunadharao
authors.forename: Vinod
authors.initials: V
authors.lastname: Raina
authors.forename: Suresh H
authors.initials: SH
authors.lastname: Advani
authors.forename: Shekhar
authors.initials: S
authors.lastname: Patil
authors.forename: Anish
authors.initials: A
authors.lastname: Maru
authors.forename: Vadavattath Padmanabhan
authors.initials: VP
authors.lastname: Gangadharan
authors.forename: Chanchal
authors.initials: C
authors.lastname: Goswami
authors.forename: Jagdev Singh
authors.initials: JS
authors.lastname: Sekhon
authors.forename: Kuraparthy
authors.initials: K
authors.lastname: Sambasivaiah
authors.forename: Purvish
authors.initials: P
authors.lastname: Parikh
authors.forename: Ashish
authors.initials: A
authors.lastname: Bakshi
authors.forename: Ranjan
authors.initials: R
authors.lastname: Mohapatra
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D053758:Nanoparticles / Q000627:therapeutic use*; D017239:Paclitaxel / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000627:therapeutic use*; D011379:Prognosis; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; C022131:cremophor; D011092:Polyethylene Glycols; D017239:Paclitaxel