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Stromal Caveolin-1 Is Associated With Response and Survival in a Phase II Trial of nab-Paclitaxel With Carboplatin for Advanced NSCLC Patients.
- Source :
-
Clinical lung cancer [Clin Lung Cancer] 2015 Nov; Vol. 16 (6), pp. 466-74. Date of Electronic Publication: 2015 May 13. - Publication Year :
- 2015
-
Abstract
- Unlabelled: In this phase II trial, carboplatin with nanoparticle albumin-bound (nab)-paclitaxel as first-line therapy for advanced non-small-cell lung cancer (NSCLC) was evaluated. Most patients had squamous cell histology. Tumor-associated stromal caveolin-1 (Cav-1) expression was correlated with improved response rate and survival in NSCLC patients who received nab-paclitaxel in this phase II trial. These results suggest Cav-1 might serve as a potential biomarker in this patient population.<br />Background: The combination of bevacizumab with platinum-based chemotherapy results in greater response rate (RR) and overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Bevacizumab is contraindicated in patients with squamous histology or hemoptysis. Nanoparticle albumin-bound (nab)-paclitaxel is a novel formulation of paclitaxel with greater dose tolerance and improved efficacy. We hypothesized that nab-paclitaxel and carboplatin would be superior to alternative doublets in advanced NSCLC patients ineligible for bevacizumab.<br />Patients and Methods: We conducted a single-arm phase II trial (NCT00729612) with carboplatin and nab-paclitaxel on day 1 of a 21-day cycle to evaluate RR (primary end point), safety, toxicity, and OS. Eligibility included: squamous histology, hemoptysis, or ongoing anticoagulation. Correlative studies included immunohistochemistry for secreted protein acid rich in cysteine (SPARC) and caveolin-1 (Cav-1).<br />Results: Sixty-three patients were enrolled. Most patients had squamous cell carcinoma (n = 48); other reasons for eligibility included hemoptysis (n = 11) and anticoagulation (n = 2). Toxicity Grade ≥ 3/4 included neuropathy, cytopenias, and fatigue. RR was 38% (24 partial response/0 complete response); 20 patients had stable disease (32%). Median progression-free survival was 5 months and median OS was 9.7 months. Immunohistochemistry for SPARC and Cav-1 was performed in 38 and 37 patients respectively. Although no association was found for SPARC expression in tumor or stroma with RR or OS, we found that higher Cav-1 levels in tumor-associated stroma was associated with improved RR and OS.<br />Conclusion: Carboplatin and nab-paclitaxel every 21 days demonstrated promising efficacy with tolerable toxicity in NSCLC patients ineligible for bevacizumab therapy. Further analysis and validation of Cav-1 and SPARC expression in tumor and stromal compartments as prognostic and/or predictive biomarkers of NSCLC or nab-paclitaxel treatment is warranted.<br />Competing Interests: The authors have stated that they have no conflicts of interest.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Albumins chemistry
Bevacizumab
Carboplatin administration & dosage
Carboplatin adverse effects
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung mortality
Contraindications
Drug Therapy, Combination
Fatigue etiology
Female
Humans
Lung Neoplasms drug therapy
Lung Neoplasms mortality
Male
Middle Aged
Nanoparticles adverse effects
Nanoparticles chemistry
Neoplasm Staging
Nervous System Diseases etiology
Paclitaxel adverse effects
Paclitaxel chemistry
Survival Analysis
Biomarkers, Pharmacological metabolism
Carcinoma, Non-Small-Cell Lung diagnosis
Caveolin 1 metabolism
Lung Neoplasms diagnosis
Nanoparticles administration & dosage
Paclitaxel administration & dosage
Stromal Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1938-0690
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical lung cancer
- Publication Type :
- Academic Journal
- Accession number :
- 26123189
- Full Text :
- https://doi.org/10.1016/j.cllc.2015.05.004