Neoadjuvant triweekly nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for Stage II/III HER2-negative breast cancer: evaluation of efficacy and safety

• Published in: Japanese journal of clinical oncology 2015-07, Vol.45 (7), p.642-649
• Main Authors: Shimada, Hiroko, Ueda, Shigeto, Saeki, Toshiaki, Shigekawa, Takashi, Takeuchi, Hideki, Hirokawa, Eiko, Sugitani, Ikuko, Sugiyama, Michiko, Takahashi, Takao, Matsuura, Kazuo, Yamane, Tomohiko, Kuji, Ichiei, Hasebe, Takahiro, Osaki, Akihiko
• Format: Article
• Language: English
• Subjects: Adult; Aged; Albumins - administration & dosage; Albumins - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - analysis; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Docetaxel; Drug Administration Schedule; Epirubicin - administration & dosage; Epirubicin - adverse effects; Female; Fluorodeoxyglucose F18; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Middle Aged; Nanoparticles; Neoadjuvant Therapy - methods; Neoplasm Staging; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Positron-Emission Tomography - methods; Radiopharmaceuticals; Taxoids - administration & dosage; Taxoids - adverse effects; Treatment Outcome
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyv055

Nanoparticle albumin-bound paclitaxel (nab-PTX) is a solvent-free paclitaxel coupled to human albumin without an associated increase in toxicity. The neoadjuvant study of primary breast cancer was planned to evaluate tumor response and safety of triweekly nanoparticle albumin-bound paclitaxel. Patients with Stage II/III HER2-negative primary breast cancer received four courses of nanoparticle albumin-bound paclitaxel 260 mg/m(2) every 3 weeks (q3w), followed by four courses of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) q3w. Tumor response after nanoparticle albumin-bound paclitaxel was histologically evaluated. In addition, the clinical response, breast-conserving rate and safety of this treatment were monitored. Among 53 patients who received nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide neoadjuvant chemotherapy, pathological complete response and near-pathological complete response were confirmed in 3 (5.7%) and 7 (13.2%) patients who had surgery, respectively. The overall objective response rate was 71.7% after completion of chemotherapy. Based on Positron Emission Tomography Response Criteria in Solid Tumors using (18)F-fluorodeoxyglucose, complete metabolic response and partial metabolic response after 2-3 courses of nanoparticle albumin-bound paclitaxel were 15.1 and 52.8%, respectively. The most common significant toxicities of q3w nanoparticle albumin-bound paclitaxel were Grade 3 muscle pain, neuropathy and febrile neutropenia, each in 1 (1.9%) patient. There were no incidences of anaphylaxis or Grade 4/5 adverse events. Neoadjuvant chemotherapy using q3w nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide was feasible in breast cancer patients with acceptable clinical response and drug tolerance, but conferred a low rate of pathological complete response. Monotherapy with q3w nanoparticle albumin-bound paclitaxel could be an appropriate substitute for solvent-based taxane in terms of therapeutic and safety management.