# Nanomedicine Interventions in Clinical Trials for the Treatment of Metastatic Breast Cancer
## 3 Results
### Nanoparticle Albumin-Stabilized Paclitaxel  
The first phase I clinical trial was performed by [PERSON] et al. and it determined the efficacy of abraxane (the first nab-paclitaxel drug approved by the US Food and Drug Administration) plus lapatinib as neoadjuvant therapy in 30 patients with stage I, II, and III breast cancer. This combination was feasible, with very few grade 3 toxicities such as rash, diarrhea, and fatigue and had a pCR of 17.9%. Though this trial had a small sample size, its results were comparable to other trials using this combination. The skin reactions in this study were similar to those previously described, and the authors emphasized the need for supportive dermatologic care for patients receiving lapatinib plus taxanes [18]. The first phase II trial was performed by [PERSON] et al., and it aimed to compare nab-paclitaxel plus doxorubicin plus cyclophosphamide plus pegfilgrastim given with or without bevacizumab in the treatment of 211 women with HER2\(-\)/NEU negative breast cancer. pCR was obtained in 35.7% of the patients treated with bevacizumab and in 21.2% of the patients treated without bevacizumab. Adverse reactions such as anemia, febrile neutropenia, nausea, and vomiting were reported in both groups [19]. Another phase II trial was performed by [PERSON] et al. and aimed to evaluate the efficacy of maintenance treatment with erlotinib plus bevacizumab after nab-paclitaxel plus bevacizumab in 55 women with metastatic breast cancer. Overall median survival was 18.1 months (95% CI, 15.6-21.7) with 5.45% mortality. Infection, neutropenia fatigue and neuropathy were the most common adverse effects [20]. [PERSON] et al. also developed a phase II trial to evaluate the efficacy and safety of treatment with abraxane and lapatinib in 60 women with HER2-positive metastatic breast cancer who had received no more than one prior chemotherapeutic regimen. In this study, a clinical benefit was witnessed for treatment with lapatinib and paclitaxel. A PFS of 39.7 (95% CI, 34.1-63.9) weeks shows clinically meaningful activity, with results consistent with other trials that assessed this combination therapy [29; 30]. Adverse events had a toxicity grade of 3 or less, and most resolved without sequelae. Non-hematologic toxicities were consistent with those reported in another clinical trial [29]. This study established a dose regimen of nab-paclitaxel (100 mg/m\({}^{2}\) IV on day 1, 8, and 15 every 28 days) in combination with lapatinib (1000 mg orally once daily on a continuous basis) in a 4-week cycle with favorable efficacy and no additional safety indications [21]. Another phase II report was performed by [PERSON] et al. where the efficacy and safety of adding bevacizumab to nab-paclitaxel plus carboplatin was determined in 33 women with stage II or III HER2-negative breast cancer. This study did not meet the expected pCR, the primary endpoint for efficacy. Still, for patients with TNBC, a longer course of neoadjuvant might increase the rate of pCR. This trial showed a higher than anticipated incidence of myelosuppression and the rate of complications was similar to that reported in other clinical trials that use bevacizumab in neoadjuvant treatment. This treatment should be further investigated [22]. [PERSON] et al. reported a phase II trial to study the efficacy of treatment with nab-paclitaxel plus gemcitabine plus bevacizumab in 48 women with metastatic breast cancer. This study met its endpoint, with 6 months PFS >60%, and had an overall survival of 24.4 months (95% CI, 18.2-29.3). Therefore, this therapeutic combination was concluded to be effective in patients with metastatic breast cancer. Toxicities were manageable, permitting long-duration therapy. The most common adverse effects were neutropenia, fatigue, thrombocytopenia, anemia, leukopenia, and dyspnea. This regimen should be further evaluated in regimens of chemotherapy plus targeted agents in metastatic breast cancer [23]. Another phase II study was performed by [PERSON] et al.