Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer

Invest New Drugs. 2012 Jun;30(3):1132-7. doi: 10.1007/s10637-011-9674-9. Epub 2011 May 3.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Albumins / adverse effects
  • Albumins / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Area Under Curve
  • Asian People
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects
  • Carboplatin / pharmacokinetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Paclitaxel / pharmacokinetics

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Carboplatin
  • Paclitaxel