First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

Abstract

Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007) is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel). A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.

Phase I study of NK105, a nanomicellar paclitaxel formulation, administered on a weekly schedule in patients with solid tumors

“…Therefore, a novel PTX formulation that can be administered without the use of such vehicles and premedication is desirable. Recently, nanoparticle albumin-bound PTX (nab-PTX, Abraxane®), which can be infused without an antiallergic premedication to prevent hypersensitivity, has been introduced into clinical use [14]. However, nab-PTX contains human albumin, suggesting a potential risk of infection.…”

A retrospective analysis of safety and efficacy of weekly nab-paclitaxel as second-line chemotherapy in elderly patients with advanced squamous non-small-cell lung carcinoma

“…Studies show that nab-paclitaxel utilizes albumin to deliver paclitaxel, resulting in a higher concentration relative to solvent-based paclitaxel. 15 Another possible contributing factor to the finding that nab-paclitaxel accumulates in the tumor is the prevalence of albumin-binding proteins, such as secreted protein, near the tumors that are acidic and rich in cysteine. 16 An obvious advantage to weekly regimens is close monitoring and an improved safety profile on average.…”

244-MPT overcomes gefitinib resistance in non-small cell lung cancer cells

“…An estimated 1.8 million new lung cancer cases occurred in 2012 worldwide, accounting for about 13% of total cancer diagnoses [ 16 ]. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of all cases [ 17 ]. Approximately 70–75% of patients with NSCLC have advanced stage disease when first diagnosed [ 18 ].…”

“…However, chemotherapy is fraught with harmful side effects such as fatigue, myelosuppression, neutropenia, diarrhea and nausea [ 20 ]. Moreover, data indicate that the response rate of advanced stage NSCLC patients to current standard combination chemotherapy is only 20–25% and the estimated 2- or 5-year survival rates are only 15- or 2%, respectively [ 17 , 21 , 22 ]. Novel therapies include the targeting of biomarkers, such as EGFR, that are commonly overexpressed in lung cancers.…”