Phase II trial of nanoparticle albumin-bound paclitaxel, carboplatin, and bevacizumab in first-line patients with advanced nonsquamous non-small cell lung cancer

J Thorac Oncol. 2009 Dec;4(12):1537-43. doi: 10.1097/JTO.0b013e3181c0a2f4.

Abstract

Introduction: Carboplatin/paclitaxel chemotherapy with bevacizumab is an accepted standard treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). The development of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has circumvented many of the infusion difficulties associated with standard solvent-based paclitaxel (in Cremophor) and offers theoretical advantages in efficacy. This trial evaluated the combination of nab-paclitaxel, carboplatin, and bevacizumab in advanced (stage IIIB/IV) nonsquamous NSCLC.

Methods: Fifty patients with stage IIIB/IV NSCLC were enrolled between October 2005 and April 2006; 48 were treated with nab-paclitaxel 300 mg/m2, carboplatin area under the curve = 6, and bevacizumab 15 mg/kg every 21 days until progression or intolerable toxicity, up to 4 cycles; an additional 2 cycles could be administered to responding patients and the physician's discretion; maintenance bevacizumab was not administered. Patient demographics included: 56% female, median age 67 years (range, 32-83), performance status 0 (52%) or 1 (48%), adenocarcinoma 86%, and stage IV disease 82%. Responding patients received a minimum of 4 cycles. The primary end point was response rate.

Results: Response rate was 31% with a stable disease rate of 54%. No complete responses were observed. Median progression-free survival was 9.8 months (range, <1-22.3), and median survival was 16.8 months. Most frequent grades 3 and 4 treatment-related toxicities were neutropenia (54%) and fatigue (17%).

Conclusions: The combination of nab-paclitaxel, carboplatin, and bevacizumab was well tolerated with moderate neutropenia. Adverse events were manageable. Survival results are encouraging. These results indicate that this combination has promising activity as first-line therapy in patients with nonsquamous NSCLC.

Publication types

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

MeSH terms

  • Adenocarcinoma, Bronchiolo-Alveolar / drug therapy
  • Adenocarcinoma, Bronchiolo-Alveolar / mortality
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Albumin-Bound Paclitaxel
  • Albumins / administration & dosage
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Carboplatin / administration & dosage
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nanoparticles / administration & dosage*
  • Neoplasm Staging
  • Paclitaxel / administration & dosage*
  • Prognosis
  • Quality of Life
  • Survival Rate
  • Treatment Outcome

Substances

  • Albumin-Bound Paclitaxel
  • Albumins
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Carboplatin
  • Paclitaxel