0000000000632642
AUTHOR
Corrado Ficorella
Does pain intensity predict a poor opioid response in cancer patients?
Abstract Aim The aim of this study was to test the hypothesis that initial pain intensity is not a predictive factor of poor opioid response in advanced cancer patients, as suggested by a recent work. Methods A secondary analysis of one-hundred-sixty-seven patients referred for treatment of cancer-related pain was conducted. Pain intensity at admission was recorded and patients were divided in three categories of pain intensity: mild, moderate and severe. Patients were offered a treatment with opioid dose titration, according to department policy. Data regarding opioid doses and pain intensity were collected after dose titration was completed. Four levels of opioid response were considered:…
Low doses of transdermal fentanyl in opioid-naive patients with cancer pain.
The aim of this study was to evaluate the effect and tolerability of low doses of transdermal (TD) fentanyl patches in opioid-naive patients with cancer pain.This was a nonrandomized, open-label, uncontrolled study in fifty consecutive opioid-naive patients with advanced cancer and moderate pain. TD fentanyl was initiated at a dose of 12 µg/h. Doses were then adjusted according to the clinical response. Pain intensity, opioid-related adverse effects, TD fentanyl doses, and quality of life were monitored over 4 weeks. The time to dose stabilization and indexes of dose escalation were also calculated.Thirty-one patients completed all 4 weeks of the study. Pain control was achieved within a me…
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. Dose- finding 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: irin…
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…
Low morphine doses in opioid-naive cancer patients with pain
Cancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization. Recent studies have proposed to skip the second "rung" of the ladder by using a so-called "strong" opioid for moderate pain. However, usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients. The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics. A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were …
The prevalent KRAS exon 2 c.35 G > A mutation in metastatic colorectal cancer patients: a biomarker of worse prognosis and potential benefit of bevacizumab-containing intensive regimens?
Bevacizumab-containing chemotherapy differently predict increased efficacy in KRAS exon 2 mutant and wild-type metastatic colorectal cancer (MCRC) patients. Mutant compared to wild-type status did not significantly affect progression-free survival (PFS) and overall survival (OS) in patients fit for first line bevacizumab-containing FIr-B/FOx regimen, and after progression. In patients unfit for intensive regimens, mutant status significantly affected PFS, while not OS. Codon 12 KRAS mutations differentially affect GTPase function, and confer worse clinical behaviour. Prognostic relevance of the prevalent c.35 G. >. A KRAS mutation was retrospectively evaluated. Fit c.35 G. >. A mutant patie…
Palliative Care in Advanced Cancer Patients: How and When? And Where?
Eduardo Bruera et al. [1] recently published an exhaustive paper in which they underscore the importance of the integration between oncology and palliative care, suggesting how and when to provide palliative care in advanced cancer patients. We agree that this integrative model allows prompt evaluation and treatment of symptoms, a reduction in costs resulting from inappropriate hospitalization, and better survival outcomes. In their conclusion, Bruera et al. [1] affirm that the two most important resources for palliative care delivery are outpatient palliative care centers and inpatient palliative care units. Although we are on the same wavelength as Bruera et al. [1], we would like to poin…
The use of fentanyl buccal tablets for breakthrough pain by using doses proportional to opioid basal regimen in a home care setting.
Abstract The dose of rapid onset opioids to be given for breakthrough cancer pain (BTcP) is controversial. Dose proportional to the basal opioid regimen seem to be safe and effective in hospital units. However, data in other less protected settings, like home care, are lacking. The aim of this open-label study was to assess the efficacy and safety in a group of patients with BTcP followed at home, after giving a dose of fentanyl buccal tablets (FBT) proportional to the opioid basal regimen, skipping the steps for dose titration. Consecutive patients admitted to a home care program presenting BTcP episodes and receiving stable doses of opioids for background pain were selected. Data from fou…
<p>Weekly alternate intensive regimen FIrB/FOx in metastatic colorectal cancer patients: an update from clinical practice</p>
Background Several trials evaluated the role of intensive regimens, made of triplet chemotherapies plus bevacizumab, as first-line treatment for patients with metastatic colorectal cancer (mCRC). We previously reported, in a Phase II prospective study, the efficacy and the tolerability of FIrB/FOx regimen, reporting interesting results in terms of received dose intensities (rDIs) and safety. Methods We reported a retrospective update of 85 patients treated with FIrB/FOx, an intensive regimen of 5-fluorouracil, bevacizumab, and weekly alternate irinotecan and oxaliplatin, to confirm its feasibility in "real life". Subgroup analyses were performed, particularly among patients treated with sta…
PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting
Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients. Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS). Results: Patients who received a first-l…
Tapentadol in cancer pain management: a prospective open-label study.
OBJECTIVES: The aim of this prospective, open-label study was to evaluate the efficacy and tolerability of tapentadol (TP) in the management of cancer pain. METHODS: A 4 weeks' prospective study was carried out in 50 opioid-naive cancer patients with moderate-severe pain. Each patient initially received twice-daily doses of slow-release TP 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity, on the basis of the clinical response. The following parameters were recorded at weekly intervals for 4 weeks: pain and opioid-related adverse effects, quality of life measured with the Spitzer score, TP escalation index percent (TPEI%) and TP escalation index in mg (TPE…
Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience
Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At…
Additional file 1 of Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study
Additional file 1.
The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes1. Additional sources of breast cancer heterogeneity may raise during the disease course. In BC patients whose disease was initially diagnosed in the early stage and subsequently progressed with metastatic involvement of one single or multiple site/s, the molecular characteristics of metastatic lesions do not necessary mimic those of the disease initially diagnosed. A well-depicted molecular landscape is crucial for subtype definition, prognostic evalu…
Second-line Eribulin in Triple Negative Metastatic Breast Cancer patients. Multicentre Retrospective Study: The TETRIS Trial
Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95…
Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma
The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…
Sleep Disturbances in Patients with Advanced Cancer in Different Palliative Care Settings.
Abstract Context Information regarding sleep disturbances in the population with advanced cancer is meager. Objectives To assess the prevalence of sleep disturbances and possible correlations with associated factors in a large number of patients with advanced cancer admitted to different palliative care settings. Methods This was an observational study performed in different settings of palliative care. A consecutive sample of patients with advanced cancer was prospectively assessed for a period of six months. Epidemiological and clinical data, treatments received in the last month, Karnofsky status, Edmonton Symptom Assessment System scores, and concomitant medical treatment were recorded.…
Sustained-release oral morphine versus transdermal fentanyl and oral methadone in cancer pain management.
The aim of this study was to compare the analgesic and adverse effects, doses, as well as cost of opioid drugs, supportive drug therapy and other analgesic drugs in patients treated with oral sustained-release morphine, transdermal fentanyl, and oral methadone.One hundred and eight cancer patients, no longer responsive to opioids for moderate pain, were selected to randomly receive initial daily doses of 60 mg of oral sustained-release morphine, 15 mg of oral methadone, or 0.6 mg (25 microg/h) of transdermal fentanyl. Oral morphine was used as breakthrough pain medication during opioid titration. Opioid doses, pain intensity, adverse effects, symptomatic drugs, were recorded at week interva…
Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine. Real-world evidence
Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5-24.9, 25-29.9, and 30.0-34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 70…
Prognostic clinical factors in patients affected by non-small-cell lung cancer receiving Nivolumab
Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab. Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC. Results: Of the more than 50 variables analyzed, five showed a signifi…
Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study
AbstractBackgroundHER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to d…
Is There Still a Role for Endocrine Therapy Alone in HR+/HER2- Advanced Breast Cancer Patients? Results from the Analysis of Two Data Sets of Patients Treated with High-Dose Fulvestrant as First-Line Therapy in the Real-World Setting: The EVA and GIM-13 AMBRA Studies
<b><i>Background:</i></b> Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. <b><i>Methods:</i></b> For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). <b><i>Res…
Evaluation of Second-line Anti-VEGF after First-line Anti-EGFR Based Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Multicenter “SLAVE” Study
: Background: The optimal anti-angiogenic strategy as second-line treatment in RAS wild-type metastatic colorectal cancer (mCRC) treated with anti-EGFR (Epidermal Growth Factor Receptor) based first-line treatment is still debated. Methods: This multicenter, real-world, retrospective study is aimed at evaluating the effectiveness of second-line Bevacizumab- and Aflibercept-based treatments after an anti-EGFR based first-line regimen. Clinical outcomes measured were: objective response rate (ORR), progression free survival (PFS), overall survival (OS) and adverse events (AEs) profiles. Results: From February 2011 to October 2019, 277 consecutive mCRC patients received Bevacizumab-based (228,…
Switching from Transdermal Drugs: An Observational "N of 1" Study of Fentanyl and Buprenorphine
The aim of this study was to confirm that the concomitant presence of transdermal fentanyl (TTS FE) and buprenorphine (TTS BU) may be feasible without important consequences, using doses presumed to be equianalgesic. A prospective "N of 1" study was carried out in a sample of volunteers with cancer pain receiving stable doses of TTS FE or TTS BU, with adequate pain and symptom control. In the study design, each patient provided data before and after a switch from one opioid to the other and then back to the previous one. Sixteen patients receiving daily stable doses of 0.6 or 1.2 mg of TTS FE were switched to TTS BU using an FE-BU ratio of 0.6-0.8. After three days, the TTS BU patch was rem…
sj-docx-1-tam-10.1177_17588359211059873 ��� Supplemental material for PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting
Supplemental material, sj-docx-1-tam-10.1177_17588359211059873 for PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting by Laura Pizzuti, Eriseld Krasniqi, Isabella Sperduti, Maddalena Barba, Teresa Gamucci, Maria Mauri, Enzo Maria Veltri, Icro Meattini, Rossana Berardi, Francesca Sofia Di Lisa, Clara Natoli, Mirco Pistelli, Laura Iezzi, Emanuela Risi, Nicola D���Ostilio, Silverio Tomao, Corrado Ficorella, Katia Cannita, Ferdinando Riccardi, Alessandra Cassano, Emilio Bria, Maria Agnese Fabbri, Marco Mazzotta, Giacomo Barchiesi, Andrea Botticelli, Giuliana D���Auria, Anna Ceribe…
Dose-finding study of oxaliplatin associated to capecitabinebased preoperative chemoradiotherapy in locally advanced rectal cancer
// Gemma Bruera 1, 2 , Mario Di Staso 3 , Pierluigi Bonfili 3 , Antonio Galvano 4 , Rosa Manetta 5 , Gino Coletti 6 , Roberto Vicentini 7 , Stefano Guadagni 2, 8 , Corrado Ficorella 2, 9 , Ernesto Di Cesare 2, 3 , Antonio Russo 4 and Enrico Ricevuto 1, 2 1 Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L'Aquila, L'Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Radiotherapy, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 4 Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo,…
EGFR genomic alterations in cancer: prognostic and predictive values.
The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy num…
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 exami…
Post-Induction Management in Patients With Left-Sided RAS and BRAF Wild-Type Metastatic Colorectal Cancer Treated With First-Line Anti-EGFR-Based Doublet Regimens: A Multicentre Study
BackgroundFew data regarding post-induction management following first-line anti-epidermal growth factor receptor (EGFR)-based doublet regimens in patients with left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) are available.MethodsThis multicenter, retrospective study aimed at evaluating clinicians’ attitude, and the safety and effectiveness of post-induction strategies in consecutive patients affected by left-sided RAS/BRAF wild-type mCRC treated with doublet chemotherapy plus anti-EGFR as first-line regimen, who did not experience disease progression within 6 months from induction initiation, at 21 Italian and 1 Spanish Institutions. The measured clinical outcomes were: p…
Additional file 2 of Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study
Additional file 2.
INfluenza Vaccine Indication during therapy with Immune checkpoint inhibitors: A multicenter prospective observational study (INVIDIa-2)
BackgroundUntil now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs).MethodsThe prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety.ResultsThe study enrolle…
Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting
We analyzed data from 738 HER2‐positive metastatic breast cancer (mbc) patients treated with pertuzumab‐based regimens and/or T‐DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression‐free survival at first‐line (mPFS1) was 12 months. Pertuzumab as first‐line conferred longer mPFS1 compared to other first‐line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second‐line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T‐DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing b…
A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: A real-world experience
We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreat…
Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study
The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival a…