Abstract Olanzapine is an atypical antipsychotic agent that blocks multiple neuronal receptors involved in the nausea and vomiting pathways. It has therefore been studied for the prevention and ...treatment of chemotherapy-induced emesis and in patients in palliative care presenting nausea and vomiting refractory to standard antiemetics. Some studies have shown that olanzapine was not inferior to aprepitant in the prophylaxis of highly and moderately emetogenic chemotherapy and that it increased the rate of complete response when added to a combination of a 5-HT3 antagonist, aprepitant and dexamethasone. These studies present so many shortcomings, however, that they do not permit us to draw any firm conclusions. Oral olanzapine showed superior antiemetic efficacy to metoclopramide as rescue treatment to control breakthrough emesis induced by chemotherapy. However, an oral formulation is not appropriate because in patients with vomiting or severe nausea the mere ingestion of an oral drug could induce emesis. Finally, in palliative care olanzapine could control or reduce the intensity of nausea and vomiting refractory to standard antiemetics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We have observed the Andromeda galaxy, Messier 31 (M31), at 6.7 GHz with the Sardinia Radio Telescope. We mapped the radio emission in the C-band, re-analyzed WMAP and Planck maps, as well as other ...ancillary data, and we have derived an overall integrated flux density spectrum from the radio to the infrared. This allowed us to estimate the emission budget from M31. Integrating over the whole galaxy, we found strong and highly significant evidence for anomalous microwave emission (AME), at the level of Jy at the peaking frequency of 25 GHz. Decomposing the spectrum into known emission mechanisms such as free-free, synchrotron, thermal dust, and AME arising from electric dipole emission from rapidly rotating dust grains, we found that the overall emission from M31 is dominated, at frequencies below 10 GHz, by synchrotron emission with a spectral index of , with subdominant free-free emission. At frequencies 10 GHz, AME has a similar intensity to that of synchrotron and free-free emission, overtaking them between 20 and 50 GHz, whereas thermal dust emission dominates the emission budget at frequencies above 60 GHz, as expected.
The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor ...quality of tested products limit the possibility to offer generalizable results.
We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms.
In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6−day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038).
In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background To report on anthracycline-based chemotherapy in a retrospective case-series analysis of solitary fibrous tumour (SFT) patients treated within the Italian Rare Cancer Network. ...Patients and methods We reviewed a set of SFT treated with chemotherapy since 2002, focusing on anthracycline, administered alone or in combination with ifosfamide. Responses to ifosfamide as a single agent were also evaluated. Pathologic diagnosis was centrally reviewed, distinguishing typical, malignant (MSFT) and dedifferentiated (DSFT) subtypes. Results Among 42 SFT patients treated with chemotherapy, we selected 31 cases (mean age: 62 years; locally advanced/metastatic: 13/18; front-line/further line: 25/6; typical/MSFT/DSFT/not assessable: 1/17/12/1) who received anthracycline-based chemotherapy (anthracycline monotherapy: eight; anthracycline + ifosfamide: 23). 30 patients are evaluable for response. Best response by Response Evaluation Criteria in Solid Tumours (RECIST) was: partial response (PR): 6 (20%), stable disease (SD): eight (27%), progressive disease (PD): 16 (53%) cases. Responses were confirmed after 3 months. Median progression-free survival (PFS) was 4 (range 2–15) months, with 20% of patients being progression-free at 6 months. PR was found in 2/18 (11%) MSFT and 4/12 (30%) DSFT, with a median PFS of 3.5 and 5 months in MSFT and DSFT, respectively. 19 patients received high-dose prolonged-infusion ifosfamide (front-line/further line: 11/8; typical/MSFT/DSFT: 0/15/4) with two (10%) PR, five (26%) SD, 12 (63%) PD. Conclusions This retrospective series suggests that in SFT anthracyclines have a degree of antitumour activity in the range of soft tissue sarcoma chemotherapy. Ifosfamide monotherapy seemed to have lower activity. A higher response rate was observed in DSFT in comparison to MSFT. Studies on targeted therapies are ongoing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + ...dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis.
A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2–4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2–3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2–5 after chemotherapy.
Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137M + D. Day 1 results were similar in both arms. On day 2–5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments.
In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity.
NCT00869310.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and ...well-differentiated/dedifferentiated liposarcoma (LPS).
The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32.
Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients 52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1 had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS).
While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS.
•Medical treatment in the advanced setting for retroperitoneal LPS and LMS is scarce.•A subgroup of patients treated with trabectedin, median PFS and TTP1 were 6 months and 7.5 months, respectively.•GMI was >1.33 in 52% of patients.•A subgroup of patients with low-grade LPS had a GMI >5, thus suggesting a peculiar sensitivity to trabectedin for this histotype.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
7.
New antiemetic drugs Roila, F.; Fatigoni, S.
Annals of oncology,
04/2006, Volume:
17, Issue:
suppl-2
Journal Article, Conference Proceeding
Peer reviewed
Open access
Important progress in the prophylaxis of chemotherapy-induced acute and delayed emesis has been achieved but some fundamental needs still remain that requires new, efficacious antiemetic drugs.
A ...critical review of the results of published studies of aprepitant, a new NK1 receptor antagonist, and of palonosetron, a 5-HT3 receptor antagonist with a longer half-life.
Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly increased the control of acute emesis with respect to dexamethasone and a 5-HT3 antagonist alone after cisplatin and moderately emetogenic chemotherapy. For cisplatin nausea, aprepitant combined with dexamethasone significantly increased the control of delayed emesis with respect to dexamethasone alone, while for moderately emetogenic chemotherapy aprepitant is superior to a 5-HT3 antagonist in the control of delayed emesis. Palonosetron showed superior or similar efficacy to ondansetron and dolasetron in patients submitted to moderately emetogenic chemotherapy and similar efficacy to ondansetron in patients submitted to cisplatin.
More studies are necessary comparing aprepitant alone or combined with dexamethasone with respect to the recommended antiemetic drugs for the prevention of delayed emesis induced by cisplatin and moderately emetogenic chemotherapy as well as for palonosetron combined with dexamethasone with respect to other 5-HT3 antagonists combined with dexamethasone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array ...observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95 / 150 / 220 GHz dataset. The Q / U maps now reach depths of 2.8, 2.8, and 8.8 μ KCMB arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈ 600 square degrees at 95 GHz and ≈ 400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed Λ CDM + r + dust + synchrotron + noise . The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r0.05 < 0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ ( r ) = 0.009 . These are the strongest constraints to date on primordial gravitational waves.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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