Background Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in ...the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF. Methods We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated. Results No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent. Conclusions Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.
Summary Background Trastuzumab—a humanised monoclonal antibody against HER2—has been shown to improve disease-free survival after chemotherapy in women with HER2-positive early breast cancer. We ...investigated the drug's effect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study. Methods HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23·5 months (range 0–48 months). The primary endpoint of the trial was disease-free survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005–002385–11. Findings 97 (5·7%) patients randomised to observation alone and 58 (3·4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0·66 (95% CI 0·47–0·91; p=0·0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0·64 (0·54–0·76; p<0·0001). Interpretation Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years. The emergence of this benefit after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.
Numerous patient- and disease-related factors must be considered when deciding a treatment approach for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) ...metastatic breast cancer. Hormone therapy (HT) is generally the first option in the absence of compelling reasons for chemotherapy (e.g., rapidly progressive visceral disease). After failure of first-choice HT, alternative HT options are usually attempted until hormone resistance occurs and chemotherapy becomes the treatment of choice. The first two patients presented herein experienced prolonged disease control with third-line eribulin after two lines of HT. The third report involves a case of male breast cancer which typically presents as the HR+/HER2- phenotype. Eribulin in the second line provided prolonged clinical improvement and was well tolerated.
