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Background: EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel (low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens. Methods: Overall, 169 previously untreated GC patients were randomized between EOX (arm A) and low-TOX (arm B). The primary endpoint was progression-free survival (PFS), while secondary ones were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and tolerability. The study was designed to detect a 35% (80% power at a two-sided 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events. Results: At the cut-off date of interim analysis, median PFS was 6.3 months [95% confidence interval (CI) 5.0–8.1] in arm A vs 6.3 months (95% CI 5.0–7.8) in arm B, without statistical difference. OS was comparable in the two arms: 12.4 in arm A (95% CI 9.1–19.2) vs 11.5 months in arm B (95% CI 8.6–15.0). ORR was 33% and 24%, while DCR was 68% and 67%, respectively. Treatment modification (91% vs 78%, P = 0.017) and number of patients with CTC grade ≥ 3 adverse events (42 vs 35) were higher in arm B. Conclusions: A triplet regimen based on the fractional dose of docetaxel achieves no improvement over EOX which remains a potential standard treatment in many patients with inoperable, locally advanced or metastatic GC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event with cancer chemotherapy, despite the availability of effective antiemetic agents. This is a prospective observational study of Italian breast cancer patients treated with anthracycline plus cyclophosphamide (AC), assessed CINV incidence, adherence to national antiemetic guidelines (AIOM 2012), and the relationship with CINV outcomes.Methods: Patients with breast cancer scheduled to receive their first cycle of an AC-based regimen were enrolled at 12 Italian centers and their clinical data prospectively recorded. CINV incidence was assessed from patient diaries after the first chemotherapy cycle. The relationship between guideline adherence and CINV outcomes was examined using multiple logistic regression.Results: The overall incidence rates of nausea and vomiting among 246 evaluable patients were 63.0 and 25.4%, respectively. Most patients received a 5-HT3-RA agent and dexamethasone for acute phase CINV prophylaxis, whereas a triple combination including aprepitant (NK1-RA), consistent with national guidelines, was used in only 45.5% of cases. In the delayed phase, the guideline adherence was 48.8%, while the overall adherence was 43.5%. After adjusting for confounding factors, adherence to antiemetic prophylaxis guidelines was associated with a significant reduction in the odds of three endpoints, namely any nausea, "significant nausea," and vomiting (OR = 0.49, OR = 0.54, and OR = 0.48, respectively), and a 90% increase in the odds of overall complete protection (OR = 1.90).Conclusions: CINV is still a critical issue in AC-treated patients, despite antiemetic treatment. Non-adherence to antiemetic guidelines may lead to poorer outcomes and indicates the need for strategies to enhance the use of guidelines in clinical practice. [ABSTRACT FROM AUTHOR]

Over the years, thanks to the addition of new generation systemic agents, as well as the use of more advanced and precise radiotherapy techniques, it was able to obtain a high curability rate for breast cancer. Anthracyclines play a key role in the treatment of breast disease, with a well-known benefit on disease-free survival of patients with positive nodal status. Trastuzumab have shown a significant outcome advantage after 1-year administration in case of HER2-positive disease. Unfortunately, significant increase in cardiotoxicity has been observed after anthracyclines and trastuzumab therapies. Even though the cardiology and oncology community strongly recommend a cardiotoxicity prevention strategy for this subset of patients, there is still no consensus on the optimal patient's approach. We aimed to review the published and ongoing researches on cardioprevention strategies and to present the SAFE trial (CT registry ID: NCT2236806; EudraCT number: 2015-000914-23). It is a randomized phase 3, four-arm, single-blind, placebo-controlled study that aims to evaluate the effect of bisoprolol, ramipril or both drugs, compared to placebo, on subclinical heart damage evaluated by speckle tracking cardiac ultrasound in non-metastatic breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified.Methods: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out.Results: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075).Conclusions: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the endocrinological and clinical activity of a new slow-release formulation of leuprolide acetate in breast cancer patients. Methods: A total of 50 pre- or perimenopausal patients with early- or late-stage breast cancer who were candidates for endocrine treatment were included in the study and randomly allocated to receive either 3.75 mg of leuprolide acetate every month or 11.25 mg of leuprolide acetate every 3 months. Patients were treated until disease recurrence or progression or for a maximum of 24 months. Treatment outcome, side effects, and serum levels of gonadotrophins, estradiol, progesterone, and Δ4-androstenedione were analyzed at different time points. Results: In all, 23 patients were allocated to the monthly formulation and 27, to the 3-monthly formulation. The median time on treatment was comparable. There was no evidence of any difference in clinical outcome or drug-induced side effects, hot flushes being recorded in about 50% of patients in both groups. Altogether, 35 patients were actively menstruating at the beginning of treatment; all of them became amenorrhoic after 3 months and remained so until treatment with leuprolide was continued, irrespective of the allocated treatment. All endocrine parameters, particularly estradiol levels, were suppressed to a similar extent. Conclusions: The present results indicate that the two formulations exert a comparable estrogen-suppressive effect and warrant further study of the 3-monthly formulation of leuprolide acetate in breast cancer patients. [ABSTRACT FROM AUTHOR]

A group of 73 patients with advanced renal cell carcinoma, treated in different phase II trials with interferon α and/or interleukin-2, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were very similar across studies and included ECOG performance status ≤2, measurable or evaluable disease and no CNS metastases. The overall response rate was 8%. The overall survival was 33% at 2 years and 18% at 1 year. In the univariate analysis three prognostic factors were correlated with disease outcome: ECOG performance status (0 versus ≥1), time from diagnosis to treatment (≤12 months versus >12 months) and number of metastatic sites (1 versus ≥2). Multivariate analysis identified ECOG performance status and number of metastatic sites as important prognostic factors for survival. The true impact on patient survival of the selection of patients rather than the treatment itself should be evaluated in controlled trials. [ABSTRACT FROM AUTHOR]

The pathogenesis and progression of breast cancer involve complex interactions between hormones and polypeptide growth factors such as insulin-like growth factor-I (IGF-I). IGF-I has been found in stromal fibroblasts derived from malignant and benign breast tissue and it is a mitogen for several breast cancer cell lines. It circulates bound to specific high-affinity binding proteins, which could act as either positive or negative modulators of tumorigenesis. This study has been addressed to characterize IGF-I and its binding proteins in the serum of 85 unselected patients with early breast cancer. The IGF-I concentration was assessed by radioimmunoassay of 69 out 85 samples before and after dissociation of the IGF-I and IGF-binding protein (IGF-BP) complex whereas IGF-BP of all 85 sera were analyzed by Western ligand blotting; estradiol and progesterone were measured by radioimmunoassay in native serum samples. In our study no differences in IGF-I serum levels between pre- and post-menopausal patients were observed. Patients with higher estradiol and progesterone serum levels did not present different IGF-I concentrations compared to patients with lower serum levels. Furthermore, IGF-I median values were not found to depend on estrogen receptor (ER) status. A heterogeneous quali-quantitative molecular pattern of binding proteins was detected: IGF-BP3 and IGF-BP1 were the most and the least expressed respectively. No correlations between ER status, or parameters related to the hormonal status, and IGF-I or binding proteins expression were observed. No significant differences in IGF-I concentration and IGF-BP expression were observed between cancer patients and a control group matched for age and menopausal status. Finally, preliminary collection of 20 sera derived from patients with late breast cancer was analyzed for IGF-I and its binding proteins content. [ABSTRACT FROM AUTHOR]