Efficacy and safety of weekly intravenous nanoparticle albumin‐bound paclitaxel for non‐small cell lung cancer patients who have failed at least two prior systemic treatments

Abstract

BackgroundThe study was conducted to evaluate the efficacy and safety of weekly intravenous nanoparticle albumin‐bound paclitaxel (NAB‐paclitaxel) treatment in patients with advanced non‐small‐cell lung cancer (NSCLC) who have undergone multi‐line therapy, and to investigate the association of secreted protein acidic and rich in cysteine (SPARC) expression status with clinical outcome.MethodsSixty‐four patients who received NAB‐paclitaxel treatment (130 mg/m2 on days 1 and 8 of a 21 day cycle) as third line or further systemic treatment from 1 May 2011 to 30 June 2014 were included in this retrospective analysis. Tumor tissue was available in 28 patients for analysis of SPARC expression by immunohistochemistry.ResultsSixty‐two patients had response evaluation and complete survival follow‐up data; 83.9% received the weekly NAB‐paclitaxel as fourth‐line treatment or beyond. The objective response and disease control rates (n = 62) were 16.1% (10/62) and 64.5% (40/62), respectively. The median progression‐free and overall survival rates were 3.7 (95% confidence interval 2.6–4.8) and 9.8 months (95% confidence interval 6.9–12.8), respectively. Previous treatment with taxane did not affect the response to NAB‐paclitaxel. The main grade 3–4 toxicities experienced were neutropenia (9.4%) and leukopenia (7.8%). Patients with SPARC expression in tumor stroma but not in cancer cells had poorer progression‐free survival compared with those with negative SPARC expression in tumor stroma cells (3.3 vs. 5.0 months, P = 0.036).ConclusionWeekly NAB‐paclitaxel might be effective for heavily pretreated NSCLC patients. SPARC expression in tumor stroma cells might be a potential negative predictor of NAB‐paclitaxel.

Nab-paclitaxel in combination with Bevacizumab in patients with non-squamous non-small cell lung cancer after failure of at least one prior systemic regimen

“…This is also consistent with the known safety profiles of nab-PTX and bevacizumab [21][22][23]30]. Using nab-PTX alone, the rates of grade 3-4 leukopenia, neutropenia, and anemia have been reported to be 5%-49%, 2%-69%, and 0%-32% [24,27,28,[37][38][39][40]. In a study of nab-PTX combined with carboplatin, neutropenia, thrombocytopenia, and anemia were observed in 28.0%, 12.0%, and 8.0% of the patients, respectively [41].…”

“…The results showed that the ORR and DCR were 26.5% and 82.4%, respectively; the median PFS and OS were 6.0 and 11.0 months, respectively. Previous studies of nab-PTX alone in second or further line treatment of NSCLC reported a PFS of 3.5-6.6 months and an OS of 6.8-15.7 months, with ORRs ranging from 16.1%-35.5% [27,28,[37][38][39][40]. A study of nab-PTX combined with carboplatin reported a PFS of 4.0 months and an OS of 14.0 months [41].…”

Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

“…[65]. The positive example of using albumin nanoparticles in antitumor treatment is confirmed by a successful application and FDA approval of Abraxane ® (Celegene Corporation, Summit, NJ, USA) (paclitaxel incorporated in albumin nanoparticles for a metastatic breast cancer, non-small cell lung carcinoma, pancreatic cancer, cervical cancer [66,67,68,69,70]. Albumin based nanoparticles loaded with lapatinib (triple negative breast cancer and HER2-positive breast cancer), gemcitabine (pancreatic cancer), siRNAs (breast and lung cancers), gold nanoparticles for NSCLC, photosensitizers are also being developed [71,72,73,74,75,76,77].…”

SPARC acts as a mediator of TGF‐β1 in promoting epithelial‐to‐mesenchymal transition in A549 and H1299 lung cancer cells

“…The anti‐cancer agent azacitidine can upregulate the SPARC expression in tumors, and then promote the accumulation of albumin‐bound drugs at tumor site . NAB‐paclitaxel has been reported have convincing antitumor activity for the treatment of advanced NSCLC .…”