Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry

Purpose The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib. Methods HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry. Patients with ≥ 4 positive axillary lymph nodes (N +) or 1–3 N + with tumor size ≥ 5 cm and/or histologic grade 3 and/or Ki67 ≥ 20%, who had undergone surgery with curative intent and had received anthracyclines ± taxanes and endocrine therapy in the neoadjuvant and /or adjuvant setting were included. We performed analysis of Invasive Disease-Free Survival (iDFS), Distant Disease-Free Survival (dDFS) and Overall Survival (OS) at 5 and 10 years, as well as yearly (up to 10) of Invasive Relapse Rate (IRR), Distant Relapse Rate (DRR) and Death Rate (DR). Results A total of 1,617 patients were analyzed from the GEICAM-9906 (312), GEICAM-2003–10 (210), and GEICAM-2006–10 (160) trials plus 935 from El Álamo IV. With a median follow-up of 10.1 years, the 5 and 10 years iDFS rates were 75.2% and 57.0%, respectively. The dDFS and OS rates at 5 years were 77.4% and 88.8% and the respective figures at 10 years were 59.7% and 70.9%. Conclusions This data points out the need for new therapies for those patients. A longer follow-up of the monarchE study to see the real final benefit with abemaciclib is warranted

Modulation of Oxidative Stress by Ozone Therapy in the Prevention and Treatment of Chemotherapy-Induced Toxicity: Review and Prospects

(1) Background: Cancer is one of the leading causes of mortality worldwide. Radiotherapy and chemotherapy attempt to kill tumor cells by different mechanisms mediated by an intracellular increase of free radicals. However, free radicals can also increase in healthy cells and lead to oxidative stress, resulting in further damage to healthy tissues. Approaches to prevent or treat many of these side effects are limited. Ozone therapy can induce a controlled oxidative stress able to stimulate an adaptive antioxidant response in healthy tissue. This review describes the studies using ozone therapy to prevent and/or treat chemotherapy-induced toxicity, and how its effect is linked to a modification of free radicals and antioxidants. (2) Methods: This review encompasses a total of 13 peer-reviewed original articles (most of them with assessment of oxidative stress parameters) and some related works. It is mainly focused on four drugs: Cisplatin, Methotrexate, Doxorubicin, and Bleomycin. (3) Results: In experimental models and the few existing clinical studies, modulation of free radicals and antioxidants by ozone therapy was associated with decreased chemotherapy-induced toxicity. (4) Conclusions: The potential role of ozone therapy in the management of chemotherapy-induced toxicity merits further research. Randomized controlled trials are ongoing

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. (2) Methods: The aims of this works are: (a) to summarize the potential mechanisms that could induce CIPN by the most relevant drugs (platinum, taxanes, vinca alkaloids, and bortezomib), with particular focus on the role of oxidative stress; (b) to summarize the current situation of prophylactic and treatment approaches; (c) to describe the action mechanisms of ozone therapy to modify oxidative stress and inflammation with its potential repercussions for CIPN; (d) to describe related experimental and clinical reports with ozone therapy in chemo-induced neurologic symptoms and CIPN; and (e) to show the main details about an ongoing focused clinical trial. (3) Results: A wide background relating to the mechanisms of action and a small number of experimental and clinical reports suggest that ozone therapy could be useful to prevent or improve CIPN. (4) Conclusions: Currently, there are no clinically relevant approaches for the prevention and treatment of stablished CIPN. The potential role of ozone therapy in this syndrome merits further research. Randomized controlled trials are ongoing