Monica Di Battista

Maintenance therapy in non-small cell lung cancer

Several randomized trials have investigated the role of maintenance treatment for patients with advanced non-small cell lung cancer (NSCLC) not progressed after completion of first-line chemotherapy, with good performance score (PS) and no persistent chemotherapy-induced toxicity. Two separate strategies have been developed: the immediate use of non-cross-resistant drug (switch maintenance or early second-line therapy) or the continuation of platinum partner alone (continuation maintenance) or in combination with other drug (combination maintenance). Here we discuss how the benefits demonstrated in these studies may change clinical practice (in terms of potential toxicity and costs) and reflect on factors that may identify subgroups of patients who might benefit from maintenance therapy in general, and which maintenance therapy specifically.

Third- and further-line therapy in advanced non-small-cell lung cancer patients: an overview

Non-small-cell lung cancer (NSCLC) treatment has led to improved efficacy and compliance due to individual tailoring of the therapeutic options and the use of strategies based on both clinical characteristics and histological and biological features of the disease. In nonsquamous NSCLC, novel agents, such as pemetrexed and bevacizumab, have improved survival in the first-line setting. Maintenance therapy with pemetrexed and erlotinib resulted in improved progression-free survival compared with second-line therapy at disease progression. In the second-line setting, pemetrexed improves survival in nonsquamous NSCLC compared with docetaxel, and erlotinib has shown a survival benefit compared with best supportive care in patients who did not previously receive an EGF receptor inhibitor. Although the benefit of first- and second-line treatment over best supportive care alone has been firmly established, the role of further-line treatment remains controversial. This article summarizes the state-of-the-art treatments in this setting.

Outcomes of Platinum-Sensitive Small-Cell Lung Cancer Patients Treated With Platinum/Etoposide Rechallenge: A Multi-Institutional Retrospective Analysis.

UNLABELLED Small-cell lung cancer has a high chemotherapeutic sensitivity but with disappointing outcome results. Patients with “sensitive disease” are those who respond to treatment with a long relapse-free interval (RFI): in these cases rechallenge with first-line chemotherapy might represent a therapeutic opportunity. Our largest retrospective experience confirmed that rechallenge is feasible with interesting outcome results; there are no statistical differences between RFI and outcome. INTRODUCTION Patients with small-cell lung cancer (SCLC) that progresses after first-line (FL) chemotherapy have a poor prognosis and second-line (SL) chemotherapy has limited efficacy. Patients whose disease relapses/progresses > 90 days after FL platinum-based treatment are considered platinum-sensitive and could be rechallenged with a similar regimen. We conducted a multicenter retrospective analysis to evaluate outcomes of SCLC patients rechallenged with platinum/etoposide. PATIENTS AND METHODS Records of all SCLC patients treated in 7 institutions between January 2007 and December 2011 were reviewed. The primary end point was overall survival from the time of rechallenge (OS-R); secondary end points were progression-free survival (PFS) and overall survival from the time of diagnosis (OS-D). Survival curves were calculated using the Kaplan-Meier method. RESULTS Of the 2000 SCLC patients identified, 112 (5.6%) had sensitive disease treated with rechallenge platinum/etoposide; 65% were men with a median age of 64 years. At the time of diagnosis, 44% of patients had limited disease, 82% had an Eastern Cooperative Oncology Group performance status of 0 to 1. A median of 4 cycles of rechallenge was administered. Tumor response was 3% for complete response and 42% for partial response, 19% of patients maintained stable disease, 27% progressive disease, and 9% were not evaluable. Median PFS from the time of rechallenge was 5.5 months (95% confidence interval [CI], 4.4-6.3). Median OS-R and OS-D were 7.9 months (95% CI, 6.9-9.7) and 21.4 months (95% CI, 19.8-24.1), respectively. Subgroup analysis according to relapse-free interval (90-119 vs. 120-149 vs. > 150 days) did not show any statistically significant difference in PFS or OS-R. CONCLUSION The outcome for SL chemotherapy for SCLC is poor. Rechallenge platinum/etoposide is a reasonable option with potentially better outcomes than standard chemotherapy.

Resistance to antiangiogenic therapies

Angiogenesis is a key process for tumoral growth, which has become a main target for anticancer treatments. A wide number of agents targeting both VEGF and its receptor have recently become standard treatments for different tumor types. Unfortunately, most of the tumors become resistant to these agents after few months of treatment. Different mechanisms of resistance to antiangiogenic drugs have been proposed and investigated; some agents demonstrated to be able to restore sensitivity to antiangiogenic drugs by blocking pathways or molecules involved in the resistance in preclinical models. Biomarkers for the prediction of response or resistance to antiangiogenic agents are under evaluation.

The role of systemic and targeted therapies in brain metastases

For many years, brain metastases (BMs) have been considered as the final stage of a disease course and engendered skepticism about the efficacy of treatments. Local treatments, mainly, whole-brain radiotherapy have been the standard of care, whereas chemotherapy has been considered of limited efficacy due to the potential role of blood–brain barrier.

First-Line Platinum-Based Chemotherapy Re-challenge in Sensitive Small Cell Lung Cancer (SCLC): A Standard Treatment?

Small cell lung cancer (SCLC) has typically high sensitivity to chemotherapy and radiotherapy, although greater part of patients with limited disease (LD) and all patients with extended disease (ED) will develop disease relapse or progression, with an overall survival of 2-4 months in case of only best supportive care

The percentage of Epidermal Growth Factor Receptor (EGFR)-mutated neoplastic cells correlates to response to tyrosine kinase inhibitors in lung adenocarcinoma

Background Epidermal Growth Factor Receptor (EGFR) molecular analysis is performed to assess the responsiveness to Tyrosine Kinase Inhibitors (TKIs) in patients with Non-Small Cell Lung Cancer (NSCLC). The existence of molecular intra-tumoral heterogeneity has been observed in lung cancers. The aim of the present study is to investigate if the percentage of mutated neoplastic cells within the tumor sample might influence the responsiveness to TKIs treatment. Material and methods A total of 931 cases of NSCLC were analyzed for EGFR mutational status (exon 18, 19, 20, 21) using Next Generation Sequencer. The percentage of mutated neoplastic cells was calculated after normalizing the percentage of mutated alleles obtained after next generation sequencer analysis with the percentage of neoplastic cells in each tumor. Results Next generation sequencing revealed an EGFR mutation in 167 samples (17.9%), mainly deletions in exon 19. In 18 patients treated with TKIs and with available follow-up, there was a significant correlation between the percentage of mutated neoplastic cells and the clinical response (P = 0.017). Patients with a percentage of mutated neoplastic cells greater than 56%, have a statistical trend (P = 0.081) for higher Overall Survival (26.3 months) when compared to those with a rate of mutated neoplastic cells lower than 56% (8.2 months). Conclusions The percentage of EGFR-mutated neoplastic cells in the tumor is associated with response to TKIs. A “quantitative result” of EGFR mutational status might provide useful information in order to recognize those patients which might have the greatest benefit from TKIs.

New drugs in the treatment of elderly patients with metastatic castration-resistance prostate cancer

Treatment of prostate cancer is continually evolving and new therapies have become available. However, the management of elderly patients is challenging due to their age and comorbidities. Androgen deprivation therapy remains the mainstay treatment of hormonal-sensitive disease. Nevertheless, when disease becomes resistant to castration, docetaxel-based chemotherapy represents the standard rescue therapy irrespective of patient age. Recently, chemotherapeutic agents such as cabazitaxel and hormonal therapies such as abiraterone acetate and enzalutamide have been shown to improve survival in patients with progression of disease before or following docetaxel. This review focuses on the safety and efficacy results of these new drugs in elderly patients.

A Randomized Controlled Trial of Tong Len Meditation Practice in Cancer Patients: Evaluation of a Distant Psychological Healing Effect

CONTEXT Tong Len meditation is an important therapeutic tool in the Tibetan medicine, and it can be used for self-healing and/or to heal others. Currently, in the West, there is no scientific study concerning the efficacy of a Tong Len distant healing effect on psychological disorders in cancer patients. OBJECTIVES To evaluate a distant healing effect of Tong Len meditation on stress, anxiety, depression, fatigue, and self-perceived quality of life in cancer patients. These psychological objectives were chosen as a consequence of the limited scientific literature of present day. DESIGN We performed a double-blind randomized controlled trial on 103 cancer patients with tumors. Overall, 12 meditators used Tong Len in aid of 52 patients randomly selected as experimental group, while the remaining 51 patients constituted the control group. Patients and meditators did not know each other. All patients completed profile of mood states (POMS) and European Quality of Life-5 dimensions (EQ-5D) questionnaires before treatment (T0), after two (T1) and three months of treatment (T2), and one month after treatment cessation (T3). RESULTS With regard to the parameters related to depression, a statistically significant improvement (P = .003) was observed in the treatment group compared to controls. On the other hand, the vigor/activity parameter saw significant improvements in the control group (P = .009). Both groups exhibited significant improvements in the other factors assessed in the POMS and EQ-5D questionnaires. CONCLUSIONS This study did not provide sufficient evidence supporting an efficacy of Tong Len meditation in distant psychological healing as compared to a control condition. The research highlighted some psychological improvements through Tong Len distant meditation in a group of patients unknown to meditators. Therefore, the enhancement detected in most parameters in both treatment and control groups raises interest on in-depth analysis and evaluation of distant meditation on cancer patients to mitigate psychological problems caused by the disease.

Epidermal Growth Factor Receptor (EGFR) Mutation in Exon 19 (p.E749Q) Confers Resistance to Gefitinib in One Patient With Lung Adenocarcinoma

Introduction Nonesmall-cell lung cancer (NSCLC) accounts for approximately 70% to 80% of all cases of lung malignancies and represents one of the leading malignancies worldwide associated with a high rate of mortality. However, the prognosis differs according to both the clinical and biological features. Epidermal growth factor receptor (EGFR) mutations, which are found in approximately 10% and 60% of the Caucasian and Asian populations, respectively, and are strictly related to women nonsmokers with adenocarcinoma, have a robust predictive and prognostic significance in NSCLC. Exon