Metronomic oral vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer: results of a phase II trial (MOVE trial).

BACKGROUND: Metronomic oral vinorelbine could be a safe option for elderly patients with advanced non small cell lung cancer (NSCLC). Metronomic administration of chemotherapy leads to a cytostatic action shifting treatment target from cancer cell to tumor angiogenesis. METHODS: 43 chemotherapy naive elderly (≥ 70 yrs) PS 0-2 patients with stage IIIB-IV NSCLC were prospectively recruited. Median age was 80 yrs (M/F 36/7) with predominantly squamous histology. PS distribution was 0-1(16)/2(27) with a median of 3 serious co-morbid illnesses. Study treatment consisted of oral vinorelbine 50mg three times weekly (Monday-Wednesday-Friday) continuously until disease progression, unacceptable toxicity or patient refusal. Primary endpoints were overall response rate (ORR), clinical benefit (CB--disease response plus disease stabilization >12 weeks) and safety. Health-related QoL (HRQoL) was also assessed with FACT-L V4 scoring questionnaire. We conducted an exploratory time-course analysis of VEGF and thrombospondin-1 (TSP1) serum levels in a subgroup of patients. RESULTS: Patients received a median of 5 (range 1-21) cycles with a total of 272 cycles delivered. ORR was 18.6% with 7 partial and 1 complete responses; 17/43 experienced stable disease lasting more than 12 weeks leading to an overall CB of 58.1%. Median time to progression was 5 (range 2-21) and median overall survival 9 (range 3-29) months. Treatment was well tolerated with rare serious toxicity. Regardless of severity main toxicities observed were anemia in 44%, fatigue in 32.4%, and diarrhoea 10.5%. FACT-L v4 scores did not significantly vary during treatment. Baseline VEGF levels were lower and showed a rapid increase during treatment in non-responders pts only while TSP1 levels did not change. CONCLUSIONS: Metronomic oral vinorelbine is safe in elderly patients with advanced NSCLC with an interesting activity mainly consisting in long-term disease stabilization coupled with an optimal patient compliance (Eudra-CT 2010-018762-23, AIFA OSS on 26 February 2010).

Baseline Troponin Level and Cardiac Toxicity in HER2-positive Early Breast Cancer Patients Receiving Trastuzumab.

BACKGROUND/AIM: There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T). PATIENTS AND METHODS: Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity. RESULTS: In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06). CONCLUSION: In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.

Selection Criteria and Treatment Outcome for Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Unfit for Platinum-Based First-Line Therapy: Results of the MOON-OSS Observational Trial.

Limited evidence is available concerning the selection criteria and the outcomes of platinum unfit newly diagnosed advanced NSCLC patients receiving single-agent chemotherapy. We retrospectively collected data on consecutive, stage IIIB-IV, EGFR/ALK negative and PD-L1 < 50% NSCLC patients treated with first-line single agent chemotherapy. Baseline characteristics, outcome measures and toxicities were recorded, as well as criteria according to which treatment selection was made and what percentage of patients did not receive a first-line platinum-based chemotherapy. Two-hundred and twenty-one patients were included. Median age was 79 (range 56−92) years, M/F 165(74.6%)/56(25.4%), ECOG performance status (PS) 0/1/ ≥ 2 23(10.9%)/94(42.5%)/103(46.6%), with a median of two serious comorbidities. A median of 25% (range 10%-30%) of newly diagnosed NSCLC did not receive a first-line platinum combination. Clinical criteria according to which decision was made were older age (76.5%), comorbidities (72%), poor PS (55.2%) and familiar or social issues (10%). Single-agent treatment consisted of oral metronomic vinorelbine (MetV 78.6%), gemcitabine (Gem 10%), oral standard vinorelbine (Vin 8.2%) and other (O 3.2%). Median progression-free survival (PFS) and overall survival (OS) of single agent treatments ranged from 4.5 to 5 months and from 9 to 10.5 months, respectively. All grade toxicities did not differ among single agents, while grade 3−4 toxicities were less frequent with MetV. Up to 30% of newly diagnosed advanced EGFR/ALK negative and PD-L1 < 50% NSCLC patients do not receive a first-line platinum doublet. Main clinical selection criteria were older age (>70 years), comorbidities and poor PS. An oral treatment was frequently proposed with MetV being the most frequent choice according to its safety profile.

Incidence of Pericardial Effusion in Patients with Advanced Non-Small Cell Lung Cancer Receiving Immunotherapy.

INTRODUCTION: Cardiovascular toxicity of immunotherapy represents an underreported but potentially fatal side effect. A relatively high incidence of pericardial disease has been noticed in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively analyzed a population of patients with advanced NSCLC receiving immune checkpoint inhibitors (ICIs) looking for the presence of pericardial effusion at baseline or during treatment. The study population was compared with a control group treated with chemotherapy. All patients were checked for the presence of concomitant pleural effusion. RESULTS: We identify 60 patients (36 male/24 female, median age 70 years [range 43-81]). Prevalent histology was adenocarcinoma (65%) followed by squamous cell carcinoma (28%) and large cell or not otherwise specified (NOS) carcinoma (7%). Treatment consisted of nivolumab 3 mg/kg every 14 days (52 cases; 45 as second-line and 7 as third-line treatment) or pembrolizumab 200 mg (8 cases; all first-line treatment) for a total of 302 cycles delivered. Four out of 60 patients (6.7%) developed pericardial effusion during treatment, in two cases (3.3%) without concomitant pleural effusion, compared to 2 out of 60 (3.3%) in the control group in one case without concomitant pleural effusion (1.6%). Median time of onset was 40 days. Myocarditis was not observed. CONCLUSION: Our findings confirm pericardial effusion as a relatively frequent side effect of immunotherapy in NSCLC. Clinicians should be aware of this specific toxicity in patients with metastatic NSCLC receiving immunotherapy and refer to a cardiologist for a multidisciplinary approach.

Safety of First-line Chemotherapy with Metronomic Single-agent Oral Vinorelbine in Elderly Patients with NSCLC.

BACKGROUND/AIM: The optimal therapeutic use of metronomic vinorelbine has not yet been defined. We aimed to assess the safety of metronomic oral vinorelbine in first-line treatment of elderly patients with advanced lung cancer who were unfit for polychemotherapy. Progression-free survival, response rate and overall survival were secondary end-points. PATIENTS AND METHODS: Seventy-six patients received 50 mg of oral vinorelbine three times per week, until disease progression, patient refusal or unacceptable toxicity. Patients were evaluated for response and toxicity after one cycle of chemotherapy. The treatment was considered feasible with a grade 3/4 toxicity rate lower than 20%. RESULTS: Clinical benefit was observed in 50% of patients. Median overall survival was 8.0 months. Grade 1/2 toxicity was observed in 53 patients (69.7%), grade 3 toxicity in eight patients (10.5%). One patient had grade 4 diarrhea. CONCLUSION: Metronomic oral vinorelbine is safe in elderly patients, allowing for long-term disease stabilization with optimal patient compliance.

First-line treatment of NSCLC with bevacizumab: real world data from an Italian regional based survey.

BACKGROUND: We aimed to explore the use of platinum plus bevacizumab in a real world NSCLC population. PATIENTS AND METHODS: We retrospectively collected data from patients affected by NS-NSCLC treated with platinum plus bevacizumab across Tuscany. RESULTS: We evaluated 62 (median age: 63.5 [30-77] years) pts. All but one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7% presented with central lesion, 11.3% with brain metastasis, 38.7% with hypertension and 4.8% with mild haemoptysis. We observed a median time to progression (TTP) of 6.5 [2-37] and a median overall survival (OS) of 10.5 [2-39] months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR) of 80.6%. Safety profile was acceptable. We observed five cardiovascular events and two major bleedings with no toxic deaths. CONCLUSION: Safety and efficacy real world data are consistent with those from clinical trials even in a less selected population.

Evaluation of HER2 and p53 expression in predicting response to docetaxel-based first-line chemotherapy in advanced breast cancer.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer. METHODS: HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors. RESULTS: Median time to progression and overall survival were 9 (range 2-54) and 20 (range 3-101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p=0.05) and higher stage (p=0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53±10.21 vs 2.50±4.12, p=0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p=0.046). p53 expression was only associated with higher stage disease (p=0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter. CONCLUSION: Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.

Sorafenib in a patient with advanced hepatocellular carcinoma and serious impairment of left ventricular function: a case report.

INTRODUCTION: sorafenib, a tyrosine-kinase inhibitor, is widely used in the treatment of advanced hepatocellular carcinoma. Drug-related toxicities are generally mild but sorafenib, as other similar agents, may induce elevation of systemic arterial blood pressure levels in relation to an interaction with cardiovascular system probably mediated by HIF pathway. This side effect may be particularly critical for patients with underlying serious heart disease as it can induce acute heart failure, a life-threatening condition, and usually such patients are excluded from active treatment with tyrosine-kinase inhibitors. We report the case of a patient affected by advanced hepatocellular carcinoma and serious impairment of cardiac function treated with sorafenib without any worsening of heart function. To our knowledge this is the first report of this kind in the literature. CASE PRESENTATION: We report the case of a 74-year-old patient affected by advanced multifocal HCV-cirrhosis related hepatocellular carcinoma and severe post-ischemic fall of left-ventricular function with serious risk of cardiac functional impairment. The patient presented with an ECOG performance status of 0. Blood chemistry tests showed a substantial elevation of alpha-fetoprotein values and slight increases of bilirubin, of gamma-GT and of GOT; the absence of encephalopathy and ascites and the normality of coagulation parameters and of albumin led to classify the patient into the functional class Child-Pugh A. The patients was successfully treated with sorafenib at the reduced daily dose of 400 mg for long-time without any worsening of heart function. CONCLUSION: The presented case can offer to oncologists a clinical support to take into consideration when deciding to treat with sorafenib advanced hepatocellular carcinoma patients presenting with serious impairment of cardiac function that are usually excluded from an active treatment.

Fulvestrant treatment is associated with cholesterol plasma level reduction in hormone-receptor-positive metastatic breast cancer patients.

BACKGROUND: Fulvestrant is a pure anti-estrogen hormoal agent formally lacking any estrogen-agonist activity. We analyze the effect(s) of fulvestrant treatment on estrogen target systems in hormoe-sensitive advanced breast cancer patients. RESULTS: Patients received a median of five fulvestrant injections (range 3-19). We observed a partial response in one patient, disease stability in 21 and disease progression in 29 patients with a clinical benefit of 43.2% and a median time to progression of 5 [range 3-20] mo. Total cholesterol levels significantly decreased during treatment (219.8 +/- 45.3 vs. 201.4 +/- 42.1 mg/dl; p = 0.0054) together with LDL-cholesterol (129.7 +/- 41.39 vs. 112.3 +/- 37.1 mg/dl; p = 0.018). HDL-cholesterol and triglycerides did not show significant changes. Reduction of total and LDL-cholesterol was independent from last hormoal treatment or treatment duration. All coagulation indices and mean endometrial mucosa thickness value did not vary. METHODS: Fifty-one patients [median age 65 (range 48-82) y] were enrolled. All patients received previous hormoal treatments, with 90.2% receiving > or =2 courses. Last hormoal treatment was exemestane, letrozole, anastrozole and other in 30-10-7-4/51 patients respectively. Median withdrawal time was 18 d (range 3-1456). Complete fasting lipid blood profile and coagulation indices were assessed before fulvestrant administration, every 3 mo and at discontinuation time. Endometrial mucosa thickness was evaluated before fulvestrant administration and at end-study time. CONCLUSIONS: We observed a lipid lowering effect of fulvestrant possibly related to an influence on lipid metabolism by a mechanism in which a role could be played by progesterone receptor.