title: Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer.
abstract: BACKGROUND
  Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a Cremophor EL-free formulation of paclitaxel newly designed to avoid solvent-related toxicities. We have evaluated the safety, tolerability, pharmacokinetics, and tumor response profile of weekly nab-paclitaxel (100 mg/m(2)) infusion together with administration of carboplatin at an area under the curve (AUC) of 6 every 3 weeks in Japanese patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Nab-paclitaxel (100 mg/m(2)) was administered without steroid or antihistamine premedication as a 30-min intravenous infusion once a week in combination with carboplatin at an AUC of 6 on day 1 of repeated 21-day cycles. The pharmacokinetics of both drugs were analyzed, and both adverse events and treatment response were monitored.
  
  
  RESULTS
  Eighteen patients were enrolled in the study. The most frequent treatment-related toxicities of grade 3 or 4 were neutropenia (67%), leukopenia (50%), and anemia (22%). No severe hypersensitivity reactions were observed despite the lack of premedication, and no unexpected or new toxicities were detected. Pharmacokinetics analysis did not reveal any substantial drug-drug interactions. Seven partial responses were observed among the 18 evaluable patients, yielding a treatment response rate of 38.9%.
  
  
  CONCLUSIONS
  The combination of nab-paclitaxel (100 mg/m(2)) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan. chi-okamoto@dotd.med.kindai.ac.jp
authors.forename: Isamu
authors.initials: I
authors.lastname: Okamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubota
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nogami
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamaya
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ono
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D044466:Asian People; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D016190:Carboplatin; D017239:Paclitaxel