Opioid switching from and to tapentadol extended release in cancer patients: conversion ratio with other opioids

Objectives: The aim of this exploratory study was to assess the conversion ratios between tapentadol and other opioids in patients requiring an opioid switching. Methods: A prospective study was carried out in a convenience sample of consecutive patients admitted to an acute palliative care unit and a home care unit for a period of 1 year. Patients who were switched from/to tapentadol were selected. The initial ratio between tapentadol and other opioids, expressed as oral morphine equivalents was 1:3.3. The subsequent doses were flexible and were changed to fit the patients’ needs. Pain intensity and distress score were recorded until opioid doses were stable. In all, 37 patients were examined; 24 and 13 patients were switched from and to tapentadol, respectively. Results: The most frequent sequences were tapentadol–morphine (18 patients) in one direction, and morphine–tapentadol (8 patients) in the other direction. In the sequence tapentadol–morphine and morphine–tapentadol, the mean final tapentadol–morphine ratios were 3.9:1 (SD 2.3), and 1:4.5 (SD 3.2), respectively, which did not differ significantly from the initial established conversion ratio. A minority of patients were switched from/to tapentadol to/from other opioids. Globally, the initial ratio did not change after switching took place. Conclusion: Data suggest that a conversion ratio between tapentadol and other opioids, expressed in oral morphine equivalents could be 1:3.3 in both direction, particularly in patients who are switched in conditions of equianalgesia. The limited number of patients prevents a definitive conclusion to be drawn, and data should be interpreted with caution, given the exploratory nature of the study and the question of the low number of patients should be addressed in future studie

Relationship between background cancer pain, breakthrough pain, and analgesic treatment: a preliminary study for a better interpretation of epidemiological and clinical studies

Abstract Abstract Background: The different operational definitions of breakthrough cancer pain (BTcP) has generated unclear epidemiological data. Methods: A consecutive sample of patients was categorized on the basis of their background pain intensity, background analgesic treatment, and the presence of BTcP. Results: A total of 265 patients were surveyed; 117 patients had background pain and 91 patients presented peaks of pain intensity distinguishable from background pain. Of 117 patients with background pain, 49 patients were re-assessed after optimization of background analgesia (T1) within a mean of 8.2 days. Pain intensity significantly decreased in comparison with values recorded at admission (p\u2009<\u20090.0005); 75.5% of these patients had BTcP episodes, with a significant decrease in the number BTcP episodes in comparison with T0 (p\u2009<\u20090.0005). The mean BTcP intensity was significantly lower in comparison with T0 (p\u2009<\u20090.0005). Finally, the mean duration of untreated BTcP episodes decreased significantly in comparison with T0 (p\u2009=\u20090.016). After optimization of analgesic therapy, most patients with moderate or severe background pain receiving opioids for moderate pain, patients with moderate or severe pain receiving strong opioids, and patients with moderate or severe pain receiving no opioids moved to the group of patients with mild pain receiving strong opioids. The difference was significant (p\u2009=\u20090.022). Conclusion: Patients having good pain control after optimization of the analgesic regimen may have a decrease in number, intensity, and duration of BTcP, although the general prevalence of BTcP remains unchanged

Identification and Characterization of BRCA1 and BRCA2 Founder Mutations

A large number of cancer predisposing BRCA1/BRCA2 mutations have been reported, with a wide variety among populations. In some restricted groups, specific germline mutations in these tumor suppressor genes have been found with high predominance, due to a founder effect. We focused our review on the Italian founder mutations. The first Italian BRCA1 founder mutation, 5083del19, was found in Calabria: the presence of common allele in all carriers of this mutation (also in families with Calabrian origin living in other parts of Italy) confirmed its founder effect. The same BRCA1 mutation was identified in the Sicilian population, but only the haplotype analysis can reveal the common ancestor of these groups. Another BRCA1 founder mutation, 4843delC, was found in Sicily. Four distinct BRCA1 mutations are attributable to families original from Tuscany: 3348delAG, 3285delA, 1499insA and 5183delTGT; the latter has been shown to be a founder mutation from North-Eastern Italy. The first BRCA2 mutation was identified in Sardinia, 8765delAG, a mutation already described as a founder mutation in Jewish-Yemenite families and also in French-Canadian population but with independent origins of carriers in these three populations. BRCA2 3951del3 and BRCA1 917delTT have been described as founder mutations in Middle Sardinia and in South and Middle Sardinia, respectively. Studies regarding prevalence and penetrance of founder mutations can allow to quantify the degree of homogeneity within a population and can surely help the geneticist and oncologist to simplify their choices in the genetic testing on high-risk families, on the basis of their ethnical origin

Characterization of timing and spacial resolution of novel TI-LGAD structures before and after irradiation

The characterization of spacial and timing resolution of the novel Trench Isolated LGAD (TI-LGAD) technology is presented. This technology has been developed at FBK with the goal of achieving 4D pixels, where an accurate position resolution is combined in a single device with the precise timing determination for Minimum Ionizing Particles (MIPs). In the TI-LGAD technology, the pixelated LGAD pads are separated by physical trenches etched in the silicon. This technology can reduce the interpixel dead area, mitigating the fill factor problem. The TI-RD50 production studied in this work is the first one of pixelated TI-LGADs. The characterization was performed using a scanning TCT setup with an infrared laser and a $^90$Sr source setup

Triplet schedule of weekly 5-Fluorouracil and alternating irinotecan or oxaliplatin in advanced colorectal cancer: A dose-finding and phase II study

A weekly administration of alternating irinotecan or oxaliplatin associated to 5-Fluorouracil in advanced colorectal cancer was planned in order to evaluate a new schedule maintaining dose intensities of each drug as in double combinations and tolerability of the triplet association. The following weekly schedule was administered: irinotecan, days 1 and 15; oxaliplatin, days 8 and 22; 5-fluorouracil (5-FU) over 12-h (from 10:00 p.m. to 10:00 a.m.) timed flat infusion, days 1-2, 8-9, 15-16 and 22-23, every 4 weeks. Dosefinding and phase II study were planned. Thirteen patients were enrolled in the dose-finding study and 23 in the phase II study. The recommended doses of our study are: irinotecan 160 mg/m2; oxaliplatin 80 mg/m2; 5-FU 900 mg/m2. The doselimiting toxicity was diarrhea (35% of patients) but no cases of febrile neutropenia were observed. In 30 patients assessable for response two complete (6.7%) and 18 partial (60%) responses were observed, for an overall response rate of 66.7% (α0.05, CI±7). The triplet association using this weekly alternating schedule is an active and well-tolerated outpatient regimen. Surgical removal of residual disease was considered in 5 patients and a radical resection was performed in 5 patients (14%)