Randomized controlled trials (RCTs) have shown improvements in breast cancer outcomes from extending treatment with aromatase inhibitors (AIs) beyond the initial 5years after diagnosis. Consistency of this effect in common clinicopathologically defined subgroups was not been reported systematically. METHODS: We identified RCTs comparing extended AIs to placebo or no treatment using a systematic search of MEDLINE and a review of abstracts from key conferences between 2013 and 2016. Hazard ratios (HRs) and 95% confidence intervals (CI) for disease-free survival (DFS) were included in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: age ((60%5years versus %60%5 years), tumor size ()2cm versus %2cm), nodal status (positive versus negative), hormone receptor status (double versus single receptor expression) and receipt of adjuvant chemotherapy (yes versus no). RESULTS: Seven trials comprising 16,349 patients were analyzed. Overall, the effect of extended AIs was similar in all subgroups. Non-significantly greater effect sizes were seen in patients with larger tumors (HR for DFS 0.77 versus 0.88, p for difference=0.44), nodal involvement (HR=0.72 versus 0.83, p for difference=0.22), double hormone receptor expression (HR=0.68 versus 1.01, p for difference=0.31) and receipt of adjuvant chemotherapy (HR=0.71 versus 0.80, p for difference=0.51). CONCLUSIONS: Extended treatment with AIs is associated with similar...
COBISS.SI-ID: 3087995
Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and Methods Patients receiving 1st line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade % 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary endpoints comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy and compliance. The study had 80% power to show a 20% reduction of the incidence of grade % 2 skin rash. Results A total of 126 patients were analyzed. The incidence of skin rash grade % 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anti-cancer treatment was comparable in both arms. Conclusion The primary endpoint of decreasing grade % 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the...
COBISS.SI-ID: 2877051
Background: Glioma cells not only secrete high levels of vascular endothelial growth factor (VEGF) but also express VEGF receptors (VEGFR), supporting the existence of an autocrine loop. The direct impact on glioma cells metabolism of drugs targeting the VEGF pathway, such as Bevacizumab (Bev) or VEGFR Tyrosine Kinase Inhibitor (TKI), is poorly known. Material and Methods: U87 cells were treated with Bev or SU1498, a selective VEGFR2 TKI. VEGFR expression was checked with FACS flow cytometry and Quantitative Real-Time PCR. VEGF secretion into the medium was assessed with an ELISA kit. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS). Results: U87 cells secreted VEGF and expressed low level of VEGFR2, but no detectable VEGFR1. Exposure to SU1498, but not Bev, significantly impacted cell proliferation and apoptosis. Metabolomic studies with HR MAS showed that Bev had no significant effect on cell metabolism, while SU1498 induced a marked increase in lipids and a decrease in glycerophosphocholine. Accordingly, accumulation of lipid droplets was seen in the cytoplasm of SU1498-treated U87 cells. Conclusion: Although both drugs target the VEGF pathway, only SU1498 showed a clear impact on cell proliferation, cell morphology and metabolism. Bevacizumab is thus less likely to modify glioma cells phenotype due to a direct therapeutic pressure on the VEGF autocrine loop. In patients treated with VEGFR TKI, monitoring lipids with magnetic resonance spectroscopic (MRS) might be a valuable marker to assess drug cytotoxicity.
COBISS.SI-ID: 1813627
Hodgkin lymphoma is unusual among cancers in that it consists of a small number of malignant Hodgkin Reed-Sternberg cells in a sea of immune system cells, including T cells. Most of these T cells are reversibly inactivated in different ways and their reactivation may induce a very strong immune response to cancer cells. One way of reactivation of T cells is with antibodies blocking the CTLA-4 and especially with antibodies directed against PD-1 or the PD-L1 ligand thereby reversing the tumor-induced downregulation of T cell function and augmenting antitumor immune activity at the priming (CTLA-4) or tissue effector (PD-1) phase. Immune checkpoint inhibitors have been evidenced as an additional treatment option with substantial effectiveness and acceptable toxicity in heavily pretreated patients with Hodgkin lymphoma. Particularly PD-1 blockade with nivolumab and pembrolizumab has demonstrated significant single-agent activity in this select population.
COBISS.SI-ID: 2176891
Background: To assess efficacy and toxicity of TPF induction chemotherapy and concomitant immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and neck carcinoma.Methods: Treatment consisted of TPF induction chemotherapy (docetaxel 75 mg/m2 day 2; cisplatin, 75 mg/m2 day 2; and 5-fluorouracil 750 mg/m2 days 1-4; 4 cycles), followed by radiotherapy and concomitant weekly cetuximab, (250 mg/m2, after a loading dose of 400 mg/m2) and cisplatin (30 mg/m2).Results: 25/30 patients completed four cycles of induction chemotherapy. Six or more concomitant infusions of cisplatin and cetuximab were administered in 13/25 and 18/25 patients, respectively. The 2-year locoregional control, disease-free survival and overall survival were 47%, 47%, and 50%, respectively. Patients with grade 2 skin reaction to cetuximab had a superior outcome.Conclusion: The tested regimen was effective; however, cetuximab and low-dose cisplatin after induction TPF increased the treatment toxicity. A grade 2 skin rash correlated with improved efficacy.
COBISS.SI-ID: 1624443
In advanced squamous cell carcinoma of the head and neck, concomitant radiotherapy with cisplatin and/or cetuximab is frequently combined with cisplatin-based induction chemotherapy, which can cause severe hypomagnesemia, hypocalcemia, and hypokalemia. The aim of our study was to analyze the effects of magnesium sulfate supplementation on the incidence of hypomagnesemia, hypokalemia, and hypocalcemia during four cycles of TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy followed by concomitant radiotherapy (CRT) with cisplatin and cetuximab. Twenty-five patients included in a phase II prospective study received routine magnesium sulfate infusions before each cycle of cisplatin, and additional supplementation based on laboratory findings. During TPF, the incidence of grade 1/2 and grade 3/4 hypomagnesemia was 16% and 4%, respectively; and increased despite magnesium supplementation during CRT to 72% and 8%, respectively. During TPF, a grade 2 and grade 4 hypocalcemia occurred in 8% and 4%, respectively; and during CRT, it reached 36% (grade 1/2). Grade 1 hypokalemia only was observed during TPF (4%) and CRT (8%). The median amounts of supplemented magnesium sulfate during TPF and CRT were 20 mEq and 50 mEq, respectively. It appears that a low incidence of grade 3/4 hypomagnesemia and hypocalcemia in our patients resulted from intensive magnesium supplementation. Thorough measurements of magnesium and calcium during cisplatin-based chemoradiation protocols...
COBISS.SI-ID: 3000187