RESUMO
Sarah Nanoparticles (SaNPs) are unique multicore iron oxide-based nanoparticles, developed for the treatment of advanced cancer, following standard care, through the selective delivery of thermal energy to malignant cells upon exposure to an alternating magnetic field. For their therapeutic effect, SaNPs need to accumulate in the tumor. Since the potential accumulation and associated toxicity in normal tissues are an important risk consideration, biodistribution and toxicity were assessed in naïve BALB/c mice. Therapeutic efficacy and the effect on survival were investigated in the 4T1 murine model of metastatic breast cancer. Toxicity evaluation at various timepoints did not reveal any abnormal clinical signs, evidence of alterations in organ function, nor histopathologic adverse target organ toxicity, even after a follow up period of 25 weeks, confirming the safety of SaNP use. The biodistribution evaluation, following SaNP administration, indicated that SaNPs accumulate mainly in the liver and spleen. A comprehensive pharmacokinetics evaluation, demonstrated that the total percentage of SaNPs that accumulated in the blood and vital organs was ~78%, 46%, and 36% after 4, 13, and 25 weeks, respectively, suggesting a time-dependent clearance from the body. Efficacy studies in mice bearing 4T1 metastatic tumors revealed a 49.6% and 70% reduction in the number of lung metastases and their relative size, respectively, in treated vs. control mice, accompanied by a decrease in tumor cell viability in response to treatment. Moreover, SaNP treatment followed by alternating magnetic field exposure significantly improved the survival rate of treated mice compared to the controls. The median survival time was 29 ± 3.8 days in the treated group vs. 21.6 ± 4.9 days in the control, p-value 0.029. These assessments open new avenues for generating SaNPs and alternating magnetic field application as a potential novel therapeutic modality for metastatic cancer patients.
RESUMO
The purpose of this study was to determine the incidence and severity of epistaxis in patients treated with paclitaxel. Patients who were treated with paclitaxel filled a questionnaire regarding their general health, medications and incidents of epistaxis. Relevant clinical information was obtained from the patients' charts. Forty-seven consecutive patients were recruited to the study. Twenty-four (51%) of the patients reported epistaxis during paclitaxel therapy. Twenty-three of 39 (59%) patients who received weekly paclitaxel had epistaxis at least once during treatment, compared with one out of eight patients who were treated every 3 weeks (P = 0.045). All episodes of epistaxis were mild, occurred with normal platelets counts and did not require blood product transfusions or treatment modification. The majority of the patients experienced the first episode of epistaxis on the third week of weekly paclitaxel treatment and then repeatedly throughout therapy. It is concluded that epistaxis is a common mild side-effect of weekly paclitaxel that has not been reported previously. In this trial, epistaxis did not have any major clinical consequences. However, when paclitaxel is combined with other drugs that may cause bleeding, such as bevacizumab, physicians should be alerted to the potential risk of this phenomenon.
