V Gebbia

La Maddalena Cancer Center, Palermo, Sicily, Italy

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Publications (257)1124.11 Total impact

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    ABSTRACT: Information about symptomatic toxicities of anticancer treatments is not based on direct report by patients, but rather on reports by clinicians in trials. Given the potential for under-reporting, our aim was to compare reporting by patients and physicians of six toxicities (anorexia, nausea, vomiting, constipation, diarrhea, and hair loss) within three randomized trials. In one trial, elderly patients with breast cancer received adjuvant chemotherapy; in two trials, patients with advanced non-small-cell lung cancer received first-line treatment. Toxicity was prospectively collected by investigators (graded by National Cancer Institute Common Toxicity Criteria [version 2.0] or Common Terminology Criteria for Adverse Events [version 3]). At the end of each cycle, patients completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaires, including toxicity-related symptom items. Possible answers were "not at all," "a little," "quite a bit," and "very much." Analysis was limited to the first three cycles. For each toxicity, agreement between patients and physicians and under-reporting by physicians (ie, toxicity reported by patients but not reported by physicians) were calculated. Overall, 1,090 patients (2,482 cycles) were included. Agreement between patients and physicians was low for all toxicities. Toxicity rates reported by physicians were always lower than those reported by patients. For patients who reported toxicity (any severity), under-reporting by physicians ranged from 40.7% to 74.4%. Examining only patients who reported "very much" toxicity, under-reporting by physicians ranged from 13.0% to 50.0%. Subjective toxicities are at high risk of under-reporting by physicians, even when prospectively collected within randomized trials. This strongly supports the incorporation of patient-reported outcomes into toxicity reporting in clinical trials. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 01/2015; 33(8). DOI:10.1200/JCO.2014.57.9334 · 17.88 Impact Factor
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    ABSTRACT: The management of biliary tract cancers (BTCs) is complex due to limited data on the optimal therapeutic approach. This phase II multicenter study evaluated the efficacy and tolerability of vandetanib monotherapy compared to vandetanib plus gemcitabine or gemcitabine plus placebo in patients with advanced BTC. Patients were randomized in a 1:1:1 ratio to 3 treatment groups: vandetanib 300mg monotherapy (V), vandetanib 100mg plus gemcitabine (V/G), gemcitabine plus placebo (G/P). Vandetanib (300mg or 100mg) or placebo were given in single oral daily doses. Gemcitabine 1000mg/m(2) was intravenously infused on day 1 and day 8 of each 21-day cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints were: objective response rate (ORR), disease control rate, overall survival, duration of response, performance status and safety outcomes. 173 patients (mean age 63.6 years) were recruited at 19 centers across Italy. Median (95% confidence intervals) PFS (days) were 105 (72-155), 114 (91-193) and 148 (71-225) respectively for the V, V/G and G/P-treatment groups, with no statistical difference among them (P=0.18). No statistical difference between treatments was observed for secondary endpoints, except ORR, which slightly favored the V/G combination over other treatments. The proportion of patients reporting adverse events (AEs) was similar for the 3 groups (96.6% in V arm, 91.4% in the V/G arm and 89.3% in the G/P arm). Vandetanib treatment did not improve PFS in patients with advanced BTC. The safety profile of vandetanib did not show any additional AEs or worsening of already known AEs. NCT00753675. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 12/2014; 26(3). DOI:10.1093/annonc/mdu576 · 6.58 Impact Factor
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    ABSTRACT: Cisplatin/pemetrexed (CP) and carboplatin/paclitaxel/bevacizumab (CbTB) are standard first-line treatments for patients with advanced non-squamous non-small-cell lung cancer (NS-NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, impact on QoL could be an additional factor in the choice of treatment.
    Clinical Lung Cancer 12/2014; DOI:10.1016/j.cllc.2014.12.002 · 3.22 Impact Factor
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    ABSTRACT: We conducted a phase III multicenter randomized trial to compare the efficacy of the combination of liposome encapsulated doxorubicin (Myocet©) plus either cyclophosphamide (MC) or vinorelbine (MV). Since July 2006, 233 patients affected with metastatic breast cancer were randomized to receive the combination of Myocet (M) 60 mg/m2 i.v. plus cyclophosphamide (C) 600 mg/m2 on Day 1 of a 21‑day cycle (Arm A) or Myocet (M) at 50 mg/m2 plus vinorelbine (V) 25 mg/m2 i.v. on Day 1 and V 60 mg/m2 orally on Day 8 on a 21‑day cycle (Arm B). The primary endpoints of the study was time to progression (TTP); secondary endpoints were RR, toxicity and OS. Response was observed in 53/116 (45.7%) evaluable patients of Arm A vs. 51/112 (45.5%) of Arm B, respectively (P=NS). Median TTP was 41 weeks (95% CI, 32‑51) and 34 weeks (95% CI, 26‑39), for M/C and M/V, respectively (P=0.0234). The difference in median OS was not statistically significant (131 vs. 122 weeks; P=0.107). With regard to toxicity, patients treated with MV showed a slight increase of neutropenia and constipation, as compared to those treated with MC. No clinical signs of cardiotoxicity were observed. The MC combination remains as an unbeaten 'standard' in first line treatment of MBC.
    International Journal of Oncology 08/2014; 45(5). DOI:10.3892/ijo.2014.2604 · 2.77 Impact Factor
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    Article: New Opioids
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    ABSTRACT: Despite the skilled use of opioid analgesics, which is crucial to the relief of cancer pain, there is a lack of evidence to support many aspects of current clinical practice. Therefore, there is a significant need for more effective treatment options. New opioids have been marketed in the past years, including hydrocodone and oxymorphone. Moreover, mixed opioids with combined mechanisms of action have been developed; one such agent, tapentadol, is a centrally acting oral analgesic that possesses a combined mechanism of action: μ -opioid receptor activation with norepinephrine reuptake inhibition. Drug development strategies involving naloxone have been initiated to reduce peripheral opioid-related adverse effects. The rationale is based on the local antagonist activity of naloxone in intestinal opioid receptors and the negligible oral bioavailability of naloxone, particularly in a prolonged-release formulation. New delivery systems have been developed to provide rapid analgesia with potent opioid drugs such as fentanyl. Despite the upcoming availability of these new drugs and technologies that will add to existing types of opioid medication, their benefits and liabilities will ultimately need to be determined by the individual physician and individual patient experiencing pain.
    Journal of Clinical Oncology 05/2014; 32(16). DOI:10.1200/JCO.2013.51.8662 · 17.88 Impact Factor
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    ABSTRACT: In vitro data suggest that panobinostat (LBH589), a pan-deacetylase inhibitor, may add therapeutic benefit in the treatment of small-cell lung cancer (SCLC) with regression of tumors. This multicenter, nonrandomized phase 2 trial was designed to evaluate antitumor activity of LBH589 in patients with previously treated SCLC. Patients received LBH589 administered intravenously at a dose of 20 mg/mq (days 1-8) every 21 days. A total of 21 patients with extensive- or limited-stage SCLC were enrolled. Patients received a median of two cycles (range, 1-6). LBH589 was well tolerated, and the most common toxicities were grade 1 to 2 gastrointestinal disorders (nausea 38%, diarrhea 24%, vomiting 19%), grade 1 to 2 thrombocytopenia (14.3%). Of 19 patients evaluable for efficacy, two cases showed shrinkages more than 30% at first assessment, with time to progression of 14 and 21 weeks, respectively, and there were three long disease stabilizations of 12, 10, and 13 weeks. The study was prematurely closed because of a lack of activity. This is the first report of a pan-deacetylase inhibitor inducing tumor shrinkage and sustained stable disease in SCLC. We believe that although the trial was prematurely discontinued, modest clinical activity of LBH589 combined with a favorable safety profile in pretreated SCLC patients was observed, which warrants further exploration of the potential contribution of LBH589 in other trials.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2013; 8(8):1091-1094. DOI:10.1097/JTO.0b013e318293d88c · 5.80 Impact Factor
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    ABSTRACT: This survey was performed to draw information on pain prevalence, intensity, and management from a sample of patients who were admitted to an oncologic center where a palliative care unit (PCU) has been established for 13 years. Cross-sectional survey in an oncological department performed 1 day per month for six consecutive months. Of the 385 patients, 69.1, 19.2, 8.6, and 3.1 % had no pain, mild, moderate, and severe pain, respectively. Inpatients and patients with a low Karnofsky score showed higher levels of pain intensity (p < 0.0005). One hundred twenty-eight patients with pain or receiving analgesics were analyzed for pain management index (PMI). Only a minority of patients had negative PMI score, which was statistically associated with inpatient admission (p = 0.011). Fifty of these 128 patients had breakthrough pain (BTP), and all of them were receiving some medication for BTP. It is likely that the presence of PCU team providing consultation, advices, and cultural pressure, other than offering admissions for difficult cases had a positive impact on the use of analgesics, as compared with previous similar surveys performed in oncological setting, where a PCU was unavailable. This information confirms the need of the presence of a PCU in a high volume oncological department.
    Supportive Care in Cancer 07/2013; DOI:10.1007/s00520-013-1899-z · 2.50 Impact Factor
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    ABSTRACT: The aim was to determine if combined pemetrexed, cisplatin, and cetuximab was efficacious and safe as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC). In this single-arm, multicenter clinical trial, patients with Stage IIIB/IV nonsquamous NSCLC received first-line therapy consisting of pemetrexed (500mg/m(2)) and cisplatin (75mg/m(2)) on Day 1 (21-day cycles) plus weekly cetuximab (400mg/m(2) loading dose, then 250mg/m(2)) for 4-6 cycles. Non-progressing patients received maintenance therapy consisting of pemetrexed and cetuximab as above until disease progression. All patients received vitamin supplementation, dexamethasone, and antihistamine prophylaxis. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), 1-year survival rate, translational research (TR) and safety. Of the 113 patients receiving study drug, 109 were protocol-qualified. All patients completed ≥1 cycle of induction, and 51 (45%) and 49 (43%) patients completed ≥1 cycle of maintenance with pemetrexed and cetuximab, respectively. The ORR (n=109) was 38.5% (80% confidence interval [CI], 32.3-45.1%), all partial responses. Median PFS was 5.8 (80% CI, 4.4-6.7) months. One-year survival rate was 45% (80% CI, 39-51%). In exploratory analyses, there was some preliminary evidence of potential prognostic relationships with efficacy outcomes for epidermal growth factor receptor and thyroid transcription factor-1 protein expression, but not for KRAS mutation or for thymidylate synthase or folate receptor-alpha protein expression. Seventy-three (64.6%) patients had study drug-related Grade 3/4 adverse events (AEs). Drug-related serious AEs were reported in 31 (27.4%) patients. There were 3 (2.7%) potentially drug-related deaths on-study or within 30 days of follow up. Pemetrexed, cisplatin, and cetuximab appeared efficacious and tolerable in advanced nonsquamous NSCLC patients. The TR outcomes are hypothesis-generating given the study's size and nonrandomized nature.
    Lung cancer (Amsterdam, Netherlands) 06/2013; 81(3). DOI:10.1016/j.lungcan.2013.05.010 · 3.74 Impact Factor
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    ABSTRACT: Platinum-based chemotherapy is the standard treatment for patients with advanced non-small cell lung cancer (NSCLC), but the evidence of its efficacy among ECOG performance status (PS)2 patients is weak because these patients are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard chemotherapy in these patients. No prospective randomized trial has tested the addition of cisplatin to single-agent chemotherapy in patients with advanced NSCLC and PS2. CAPPA-2 was a multicenter, randomized phase 3 study for first-line treatment of PS2 patients with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI edition) and adequate organ function. Patients in standard arm received gemcitabine 1200mg/m(2) days 1 and 8. Patients in experimental arm received cisplatin 60mg/m(2) day 1 plus gemcitabine 1000mg/m(2) days 1 and 8. All treatments were repeated every 3 weeks, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. The study was stopped in June 2012 after the enrolment of 57 patients, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin plus gemcitabine (HR 0.52, 95% CI 0.28-0.98, p=0.039). Combination chemotherapy produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p=0.017) and higher response rate (4% vs. 18%, p=0.19), without substantial increase in toxicity. The addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC.
    Lung cancer (Amsterdam, Netherlands) 05/2013; 81(1). DOI:10.1016/j.lungcan.2013.04.008 · 3.74 Impact Factor
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    ABSTRACT: Aims and background. In recent years, the number of oral anticancer drugs used in clinical practice has rapidly increased. The Italian Society of Medical Oncology (AIOM) conducted a survey to describe the impact of the use of oral anticancer drugs on the daily activity of Italian oncology practices. Methods and study design. A survey questionnaire was distributed to the coordinators of the regional sections of AIOM. A 6-month period was considered, from January 1, 2010 to June 30, 2010. The survey addressed (1) quantitative aspects of the use of oral anticancer drugs; (2) practical aspects in the management of patients treated with these drugs; (3) issues related to treatment costs and reimbursement procedures. Results. Thirty-six questionnaires were received from institutions distributed throughout the Italian territory. Oral anticancer drugs (both chemotherapy and molecularly targeted agents) accounted for a significant proportion (17%) of prescribed treatments. Among the responding institutions, there were different dispensation procedures of oral drugs to patients: drugs were dispensed by the pharmacist (57%) or directly by the medical oncologist (23%) or nurse (20%). The medical oncologist played a major role in the communication with patients (73% alone and a further 24% in cooperation with other professional figures) and was the point of reference in the event of side effects in 97% of cases. In most cases, the reimbursement of drug costs was separated ("File F" procedure) from the flat fare received by the hospital for outpatient visits or day-hospital access. Conclusions. Optimal organization of oral anticancer treatment warrants the cooperation and integration of multiple professional figures. At least three figures are involved in patient management in the hospital: the medical oncologist, the nurse, and the hospital pharmacist. Oral anticancer treatments are associated with specific reimbursement issues: in the majority of cases, the cost of the drug is reimbursed separately from the cost of patient access.
    04/2013; 99(1):35-8. DOI:10.1700/1248.13785
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    ABSTRACT: BACKGROUND: Adherence to erlotinib could be a determinant for clinical outcome and treatment toxicity in patients with advanced non-small-cell lung cancer (A-NSCLC). PATIENTS AND METHODS: In an observational study, the Basel Assessment of Adherence Scale (BAAS), a visual analogue scale (VAS), pill counting, and missed appointment rate were used to evaluate adherence in a first cohort of patients who was prescribed erlotinib without a specifically designed management strategy and in a second cohort of patients followed by an oral treatment monitoring program. RESULTS: Adherence > 95% by BAAS at 2 months of treatment in the first and second cohorts was 72% and 84%, respectively (P = .042). Adherence by pill counting was 78% and 87% in the first and second cohorts, respectively (P = .0021). Disease control rate (DCR) (complete response [CR] + partial response [PR] + stable disease [SD]) was significantly higher in all patients whose adherence by BAAS at 2 months was ≥ 95% (P = .0266). DCR was higher in the second cohort compared with the first, being 63% (95% confidence interval [CI], 53%-72%) and 44% (95% CI, 30%-58%) in the second and the first cohort, respectively (P = .0368). A significant correlation between the number of adverse events and patient-reported adherence was observed (r = 0.105; P = .0001). CONCLUSION: Nonadherence may be related to poorer rates of response to erlotinib. Effective interventions to reduce nonadherence need to be implemented.
    Clinical Lung Cancer 01/2013; DOI:10.1016/j.cllc.2012.11.007 · 3.22 Impact Factor
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    ABSTRACT: INTRODUCTION:: The TORCH (Tarceva or Chemotherapy) trial randomized patients with advanced non-small-cell lung cancer to first-line erlotinib followed by second-line cisplatin/gemcitabine versus. standard inverse sequence. The trial, designed to test noninferiority in overall survival, was stopped at interim analysis because of inferior survival in the experimental arm. Quality of life (QoL), a secondary outcome, is reported here. METHODS:: QoL was assessed at baseline and every 3 weeks during first-line, using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 and QLQ-lung cancer specific module (LC13). Mean changes from baseline within arms were reported. QoL response and time-to-deterioration of QoL using a competing-risk approach were compared between treatment arms. RESULTS:: Six hundred and thirty patients (83%) completed baseline questionnaires. Compliance was affected by differential treatment efficacy, but was similar between arms for patients without progression or death. Significant differences in QoL responses were observed favoring chemotherapy for pain, sleeping, dyspnea, diarrhea, and favoring erlotinib for vomiting, constipation, sore mouth, and alopecia. In the small subset of patients with EGFR-mutated tumors, all selected items (global QoL, physical functioning, cough, dyspnea and pain) improved, whereas worsening or no change was observed in wild-type patients. Improvement was particularly evident in the first-line erlotinib arm as for global QoL and physical functioning. CONCLUSIONS:: QoL was impacted by differential toxicity and efficacy between arms. Functional domains and global QoL did not differ, although some symptoms were better controlled with chemotherapy in unselected non-small-cell lung cancer patients.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2012; 7(12):1830-1844. DOI:10.1097/JTO.0b013e318275b327 · 5.80 Impact Factor
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    ABSTRACT: Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence. Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned. At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation. In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.
    Journal of Clinical Oncology 07/2012; 30(24):3002-11. DOI:10.1200/JCO.2011.41.2056 · 17.88 Impact Factor
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    ABSTRACT: Tamoxifen (TAM) has been shown to be active against the bicalutamide-induced breast events (BEs) gynecomastia, and breast pain in patients with prostate cancer (PC). Optimal doses and schedules are not yet established. Debate still exists about whether prophylaxis with TAM is more effective than treatment of BEs when diagnosed. The results of a randomized study comparing TAM prophylaxis vs. TAM therapy are presented. One hundred seventy-six patients with prostate cancer (PC) who were candidates for bicalutamide monotherapy were randomized to receive TAM 20 mg daily orally within 1 month from the onset of BEs (arm A) vs. TAM 10 mg daily starting simultaneously with bicalutamide (arm B). TAM was administered for up to 1 year. BEs were evaluated by a self-administered visual analogue scale. Neither ultrasonography nor calipers were used to measure the degree of gynecomastia. In arm A, BEs showed a prevalence, increasing with time up to 78.3%. After therapy with TAM they persisted in 27.7% of cases. Two patients (3%) interrupted TAM therapy because of dizziness, and 3 patients (4%) interrupted bicalutamide therapy because of painful gynecomastia. In arm B, the prevalence of BEs was 35% after 12 months of therapy. The difference in BEs between the 2 arms was statistically significant (P < .0001). The differences in prevalence of gynecomastia and breast pain between the 2 arms both favored TAM prophylaxis (P < .0001 and P < .001, respectively). Up to 35% of patients had BEs of low intensity, never requiring bicalutamide withdrawal. Two patients (3%) interrupted the treatment because of gastrointestinal intolerance. No difference emerged between the 2 arms in terms of prostate-specific antigen (PSA) response, plasma testosterone levels, and tumor progression. Bicalutamide-induced BEs can be prevented to a significant degree by prophylaxis with TAM 10 mg/day or effectively treated with TAM therapy 20 mg/day. Persisting BEs are of higher intensity after therapy than after prophylaxis.
    Clinical Genitourinary Cancer 04/2012; 10(3):174-9. DOI:10.1016/j.clgc.2012.03.002 · 1.69 Impact Factor
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    ABSTRACT: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (> 18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m(2) or AUC 5 with gemcitabine 1000 mg/m(2)) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥ 1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5-5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25-0·54; p < 0·0001). Main grade 3 or 4 toxicities were rash (11 [13%] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.
    The Lancet Oncology 03/2012; 13(3):239-46. DOI:10.1016/S1470-2045(11)70393-X · 24.73 Impact Factor
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    ABSTRACT: Oral metronomic chemotherapy is a therapeutic option which is particularly attractive due to its ease of administration and low toxic burden. Its mechanism of action probably involves antiangiogenetic effect rather than a classical antiproliferative effect like standard maximally tolerated dose-based regimens. A retrospective analysis of 61 patients with advanced breast carcinoma was carried out with the aim of reporting activity in terms of response rate, control of tumor-related symptoms, outcome, and toxicity. All patients had hormonal therapy-resistant metastatic disease and had previously received two lines of chemotherapy. The first cohort of 22 patients received oral cyclophosphamide at 50 mg/day without interruption until re-evaluation or progressive disease, while the second cohort of 39 patients had oral cyclophosphamide at the above dose plus oral low-dose methotrexate at 2.5 mg orally twice a week. Overall, a partial response with a median duration of 6 months (range 4-9 months) according to the RECIST criteria was recorded in 18% of patients (95% confidence intervals, CI=8%-28%), and stable disease with a median duration of 5 months (range 3-8 months) was recorded in 35% of cases (95% CI=22%-49%) for a tumor growth control rate of 52%. Symptom control was achieved in 54% of cases. Toxicity was very mild and easily manageable. No cases of extra-hematological grade 3 toxicity were observed. Grade 3 non-febrile neutropenia were recorded in 3% of cases. Liver toxicity was represented by elevation of transaminases in 20 cases (33%), mainly in the cohort of patients receiving cyclophosphamide plus methotrexate. Although retrospectively recorded, the data presented in this study support the use of oral metronomic chemotherapy for patients with metastatic breast cancer. Significant clinical activity was seen in heavily pretreated patients without severe grade 3-4 side-effects. Further studies are warranted to optimise the treatment schedule and to select patients who may benefit from such an approach.
    Anticancer research 02/2012; 32(2):529-36. · 1.87 Impact Factor
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    ABSTRACT: Socioeconomic status can potentially affect prognosis of cancer patients. Our aim was to describe potential differences in demographic and clinical characteristics, treatment, and survival by education level in patients with advanced non-small cell lung cancer (NSCLC) enrolled in clinical trials of first-line treatment. Individual data of Italian patients with advanced NSCLC (stage IV, or IIIB with supraclavicular nodes or malignant pleural effusion), ECOG performance status (PS) 0-2, enrolled in four phase III randomized trials conducted between 1996 and 2005 were pooled. Information about education was available for 1680 of 1709 patients (98.3%). Patients were divided in two groups according to education level: high (patients with at least high school diploma) or low (those with less than high school diploma). Survival analyses were stratified by treatment arm within trial. There were 312 (19%) and 1368 (81%) patients with high and low education, respectively. Education level was significantly different among birth cohorts, with a time-trend toward higher education level. Patients with high education were significantly younger (median age 65 vs. 70), were less frequently unfit at diagnosis (ECOG PS2 5% vs. 16%), and their tumor type was more frequently adenocarcinoma (47% vs. 37%). Number of treatment cycles received was not significantly different between education groups. Median survival was 9.4 and 7.6 months in high and low education, respectively (p=0.012). At multivariable analysis, female sex, better PS and high education level (Hazard Ratio 0.85, 95%CI 0.73-0.99, p=0.03) were independently associated with longer survival. In Italian patients enrolled in four randomized trials of first-line chemotherapy for advanced NSCLC, high education was significantly more frequent among younger patients, and was associated with lower proportion of PS2 patients. Education level did not significantly affect number of chemotherapy cycles received. Overall survival was longer in patients with high education, after adjustment for PS and other prognostic factors. The exact underlying mechanisms of the independent prognostic role of education level are substantially unknown, but lead-time bias (anticipation in diagnosis and time to inclusion in the trial), differences in adherence to care outside the trial procedures, differences in comorbidities and life-style factors may all contribute.
    Lung cancer (Amsterdam, Netherlands) 01/2012; 76(3):457-64. DOI:10.1016/j.lungcan.2012.01.002 · 3.74 Impact Factor
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    ABSTRACT: INTRODUCTION: To date, orally administered chemotherapy and biologic agents represent a significant percentage of all antineoplastic treatments in several types of cancer, which are most likely to increase in the near future. In this scenario, the issue of adherence and persistence to oral therapy is a key issue since poor compliance to oral antineoplastic treatments may negatively influence patients' clinical outcomes and, in turn, cause an increase in costs, number of hospitalizations and time spent in the hospital. AREAS COVERED: The issue of adherence to new oral chemotherapeutic and/or biologic agents has not been deeply evaluated and data published in medical literature are quite scarce. Adherence is a multidimensional phenomenon, which may be influenced by patient- and health-care provider-related factors, anticancer therapy itself, education and socioeconomic aspects. Patients' selection plays, therefore, a key role in maximizing adherence and persistence to oral therapies. Treating health-care practitioners should first evaluate patient reliability to avoid prescribing oral treatments to patients with socioeconomic and medical conditions, which may predict poor adherence. EXPERT OPINION: Adherence and persistence to new oral biologic agents, which are linked to several side effects and whose use is constantly widening, should represent a main endpoint of clinical research in the nearest future.
    Expert Opinion on Drug Safety 12/2011; 11 Suppl 1:S49-59. DOI:10.1517/14740338.2011.645803 · 2.74 Impact Factor
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    ABSTRACT: To investigate the activity and toxicity of metronomic chemotherapy with low-dose oral cyclophosphamide (CTX) and methotrexate (MTX) in patients with metastatic CRPC that progresses after docetaxel. Patients with castration-resistant prostate cancer (CRPC) that progresses after docetaxel may benefit from receiving further chemotherapy. Patients were treated with CTX 50 mg/d p.o. plus MTX 2.4 mg p.o. twice per week without rest periods. All patients received simultaneous luteinizing hormone-releasing hormone analogue. Prostate-specific antigen (PSA) response was defined as a 50% reduction on 2 evaluations at least 4 weeks apart. Objective response was measured according to the RECIST criteria. Pain relief was analyzed with the McGill-Melzack Pain Questionnaire. Simon's 2-stage design for phase II study was used. Time to progression and progression-free and overall survival were computed. Toxicity was recorded according to the CTC-NCCN criteria. A PSA decrease ≥50% was recorded in 15 of 58 evaluable patients (25%), and objective partial response in 3 (18%) and stable disease in 4 (24%) of 17 patients with measurable disease. Disease in 10 patients (59%) progressed. Pain intensity decreased in 16 (30%), increased in 18 (33%), and remained stable in 18 (33%) patients. Five patients discontinued narcotic analgesics for a mean duration of 12 weeks. Transitory grade 3 leukopenia was observed in 4 cases (7%), grade 3 thrombocytopenia in 2 (3%), and grade 2 anemia in 4 (7%). This study demonstrates the feasibility, activity, and tolerability of oral low-dose CTX and MTX given on a metronomic schedule in patients with CRPC progressing after docetaxel-based chemotherapy.
    Urology 11/2011; 78(5):1125-30. DOI:10.1016/j.urology.2011.08.010 · 2.13 Impact Factor
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    ABSTRACT: Patient-centered home care is a new model of assistance, which may be integrated with more traditional hospital-centered care especially in selected groups of informed and trained patients. Patient-centered care is based on patients' needs rather than on prognosis, and takes into account the emotional and psychosocial aspects of the disease. This model may be applied to elderly patients, who present comorbid diseases, but it also fits with the needs of younger fit patients. A specialized multidisciplinary team coordinated by experienced medical oncologists and including pharmacists, psychologists, nurses, and social assistance providers should carry out home care. Other professional figures may be required depending on patients' needs. Every effort should be made to achieve optimal coordination between the health professionals and the reference hospital and to employ shared evidence-based guidelines, which in turn guarantee safety and efficacy. Comprehensive care has to be easily accessible and requires a high level of education and knowledge of the disease for both the patients and their caregivers. Patient-centered home care represents an important tool to improve quality of life and help cancer patients while also being cost effective.
    Therapeutics and Clinical Risk Management 09/2011; 7:387-92. DOI:10.2147/TCRM.S22119 · 1.34 Impact Factor

Publication Stats

5k Citations
1,124.11 Total Impact Points

Institutions

  • 2002–2014
    • La Maddalena Cancer Center
      Palermo, Sicily, Italy
  • 2005–2013
    • La Casa di Cura Calabrodental
      Cotrone, Calabria, Italy
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      Giovanni Rotondo, Apulia, Italy
  • 1988–2013
    • Università degli Studi di Palermo
      • Sezione di Cardiologia
      Palermo, Sicily, Italy
  • 2012
    • Instituto Universitario USP Dexeus
      Barcino, Catalonia, Spain
  • 2009
    • Ospedale Oncologico "Giovanni Paolo II" di Bari
      Bari, Apulia, Italy
    • Istituto Regina Elena - Istituti Fisioterapici Ospitalieri
      Roma, Latium, Italy
  • 2005–2006
    • American Oncology Institute
      Bhaganagar, Telangana, India