Clinical experience with nanoparticle albumin-bound paclitaxel, a novel taxane anticancer agent, and management of adverse events in females with breast cancer

Abstract

Abstract. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is currently approved in Japan for treatment of breast cancer. However, apart from phase I clinical trials, data regarding Japanese patients are scant. In the present study, the efficacy and safety of nab-paclitaxel therapy were retrospectively analyzed in 22 patients with advanced or metastatic breast cancer who were treated at the National Hospital Organization Shikoku Cancer Center between November 2010 and June 2012. The nab-paclitaxel was administered once every three weeks. The median age of the patients was 59 years. The tumors were estrogen-receptor positive and/or progesterone-receptor positive in 63.6% patients. None of the patients had HER2-positive breast cancer. The median number of treatment cycles was six (range, two to 12). Six patients exhibited a partial response; the response rate was 27.3% and the clinical benefit rate was 31.8%. The response rate and clinical benefit rate were higher in patients who received nab-paclitaxel as first-or second-line treatment. The median time to treatment failure was 127 days (range, 27-257). Major adverse events were peripheral neuropathy (59%; Grade 3, 9%), myalgia (59%), rash (45%), and nausea and vomiting (50%). The results suggest that nab-paclitaxel is a well-tolerated and clinically useful anticancer preparation. IntroductionTaxanes, along with anthracyclines, are a key component in chemotherapy for breast cancer. The Taxanes include paclitaxel and docetaxel. In Japan, weekly paclitaxel has been widely used due to good efficacy and high tolerability (1). However, since paclitaxel is relatively insoluble, polyoxyethylated castor oil (Cremophor ® EL) and ethanol have served as solvents to enhance solubility. Consequently, patients must receive premedication with corticosteroids, antihistamines and histamine-2 receptor antagonists prior to administration of paclitaxel. Despite premedication, however, ~40% patients exhibit mild hypersensitivity reactions and ~3% have serious, life-threatening reactions (2). Premedication with polyoxyethylated castor oil may also result in peripheral neuropathy and alter the pharmacokinetics of paclitaxel (3). Paclitaxel also has other solvent-related problems: Only limited types of intravenous infusion sets may be used and treating patients who exhibit alcohol intolerance is difficult (4).Nanoparticle albumin-bound (nab)-paclitaxel (Abraxane ® ) is a solvent-free, colloidal suspension of paclitaxel and human serum albumin. Compared with conventional preparations of paclitaxel, nab-paclitaxel has a number of advantages: i) No premedication to prevent hypersensitivity is required; ii) any type of intravenous infusion set may be used (with no requirement for in-line filters); iii) nab-paclitaxel may be used even in patients who are sensitive to alcohol; and iv) nab-paclitaxel may be administered at a higher dose over the course of a shorter time period than paclitaxel (5). A phase III controlled study comparing tri-weekly paclitaxel (175 mg/m 2 ) with tri-weekly n...

Dermatological adverse events with taxane chemotherapy

“…Diffuse maculopapular rashes, including SJS and TEN, can occur. The incidence of rash is comparable to that observed with the solvent-based paclitaxel (overall incidence of 4%), except in Asian populations where it appeared to affect more than a third of patients in some series [158, 160]. Nab-paclitaxel-induced SCLE is similar in all aspects to that observed with paclitaxel ( see above ) [54].…”

“…The incidence of alopecia (with monotherapy) ranges between 47% and 100% depending on the series [8, 156, 159, 160], but CIPAL has not yet been reported. The skin rashes have not been characterised clinically, although involvement of body folds and areas of friction has been reported, as have pigmentary changes [158].…”

Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin

“…One agent, Taxol (paclitaxel), is a microtubule stabilizer which leads to obstacles in chromosome separation and the cell cycle process by promoting microtubule polymerization. Taxol is widely prescribed for the treatment of solid tumors including advanced ovarian and breast cancer, non-small cell lung cancer (NSCLC) and Kaposi's sarcoma (1,2). The other is vinblastine (VBL), a microtubule destabilizer vinca alkaloid, which causes the dysfunction of cell proliferation by predominantly binding to α/β tubulin in order to disassemble microtubules.…”

Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound Paclitaxel for HER2-negative Breast Cancer

“…Although Nab-PTX has been widely used for metastatic breast cancer (7,14,15), there are only a few reports on the therapeutic efficacy and safety profile of Nab-PTX monotherapy in an upfront setting (16)(17)(18). Moreover, most studies of neoadjuvant Nab-PTX in breast cancer reported on the every-3-week (q3w) Nab-PTX administration regimen (16,17,(19)(20)(21) (22).…”