Adjuvant chemotherapy for resected biliary tract cancers: a systematic review and meta-analysis

Introduction: The use of adjuvant treatment (AT) in resected biliary tract cancers (BTC) is still controversial. No efficacy comparison has been performed between chemotherapy (CT) and chemoradiotherapy (CTRT). A systematic review of the available evidence regarding adjuvant chemotherapy (AC) in resected BTC was performed. Methods: PubMed, EMBASE, Web of Science, SCOPUS and The Cochrane Library databases were searched for relevant articles published. Only studies including at least 50 patients affected by tumors of gallbladder, intrahepatic, perihilar, and distal bile ducts were considered. Data were pooled using a random-effects model. The primary endpoint of the study was overall survival (OS). Results: Thirty studies were analyzed with a total of 22,499 patients, 3967 of whom received AC. Eleven cohorts included Western patients and 19 were Asiatic. Surgeries were classified as R0 with negative margins, R1 with positive microscopic and R2 with positive macroscopic margins. Weighted mean OS difference among experimental (AC) and control arm was 4.3 months (95% CI 0.88–7.79, P = 0.014). AC reduced the risk of death by 41% (Hazard ratio [HR] = 0.59, 95% CI 0.49–0.71; P < 0.001). Conclusions: AC administration gives an OS benefit in resected BTC. The results of prospective randomized studies are awaited in order to define the standard AT in BTC

Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis

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Chemotherapy-associated thromboembolic risk in cancer outpatients and effect of nadroparin thromboprophylaxis: results of a retrospective analysis of the PROTECHT study

<p>Abstract</p> <p>Background</p> <p>Cancer patients receiving chemotherapy are at increased risk of thrombosis. Nadroparin has been demonstrated to reduce the incidence of venous and arterial thrombotic events (TEs) by about 50% in cancer outpatients receiving chemotherapy. The aims of this retrospective analysis were to evaluate the thromboembolic risk and the benefit of thromboprophylaxis according to type of chemotherapy.</p> <p>Methods</p> <p>Cancer outpatients were randomly assigned to receive subcutaneous injections of nadroparin or placebo. The incidence of symptomatic TEs was assessed according to the type of chemotherapy. Results were reported as risk ratios with associated 95% CI and two-tailed probability values.</p> <p>Results</p> <p>769 and 381 patients have been evaluated in the nadroparin and placebo group, respectively. In the absence of thromboprophylaxis, the highest rate of TEs was found in patients receiving gemcitabine- (8.1%) or cisplatin-based chemotherapy (7.0%). The combination of gemcitabine and cisplatin or carboplatin increased the risk to 10.2%. Thromboprophylaxis reduced TE risk by 68% in patients receiving gemcitabine; with a further decrease to 78% in those receiving a combination of gemcitabine and platinum.</p> <p>Conclusions</p> <p>This retrospective analysis confirms that patients undergoing chemotherapy including gemcitabine, platinum analogues or their combination are at higher risk of TEs. Our results also suggest that outpatients receiving chemotherapy regimens including these agents might achieve an increased benefit from thromboprophylaxis with nadroparin. Clinical Trial registration number: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00951574">NCT 00951574</a></p

Attitude of Italian medical oncologists toward palliative care for patients with advanced cancer: results of the SIO project.

The aim of this survey was to describe the attitude of Italian oncologists towards palliative care. A survey on palliative care was carried out among 400 Italian oncologists. Seventy-two percent indicated that the management of patients with advanced stage cancer represents the majority of their practice. They are often involved in the management of pain (78%) and complications of chemotherapy (61%), and frequently, in the treatment of terminal patients (60%). Only 8.5% reported having frequent collaboration with psychiatrists in support of emotional and psychological patients' disturbances. About 40% are often directly involved in the management of existential or spiritual distress. Discussions on euthanasia and assisted suicide, which are illegal in Italy, took place never (68%) or occasionally (27%). Respondents agreed that all oncology centres should have access to palliative care service. These results are in line with those of the European Society of Medical Oncology survey and may be usefully employed to improve the organisation of palliative care

Careful breakthrough cancer pain treatment through rapid-onset transmucosal fentanyl improves the quality of life in cancer patients: results from the best multicenter study

Objectives: To explore the effect of breakthrough cancer pain (BTcP) treatment on quality of sleep and other aspects of the health-related quality of life (HRQoL) in patients with cancer pain. Methods: In an observational, multicenter, cohort study, cancer patients from palliative care units, oncology departments, and pain clinics and affected by BTcP were included. Enrolled patients were assessed at the four visits: T0 (baseline), T7, T14, and T28. Stable chronic background pain (numeric rating scale, NRS &lt;= 4) during the whole study period was mandatory. BTcP was treated through transmucosal fentanyl. Three questionnaires were used to measure the HRQoL: EORTC QLQ-C15-PAL, Pittsburgh Sleep Quality Index (PSQI), and the Edmonton Symptom Assessment System (ESAS). RESULTS: In 154 patients, the HRQoL showed a significant improvement for all physical and emotional characteristics in the EORTC QLQ-C15-PAL, except for nausea and vomiting (linear p-value = 0.1) and dyspnea (Linear p-value = 0.05). The ESAS and PSQI questionnaires confirmed these positive results (p &lt; 0.0001 and p = 0.002, respectively). Conclusions: This prospective investigation by an Italian expert group, has confirmed that careful management of BTcP induces a paramount improvement on the HRQoL. Because in cancer patients there is a high prevalence of BTcP and this severe acute pain has deleterious consequences, this information can have an important clinical significance

Phase II Randomized Study of Vandetanib Plus Gemcitabine or Gemcitabine Plus Placebo as First-Line Treatment of Advanced Non–Small-Cell Lung Cancer in Elderly Patients

Introduction:The aim of the present study was to evaluate the efficacy and tolerability of vandetanib plus gemcitabine (V/G) compared with gemcitabine alone in elderly patients with untreated advanced non–small-cell lung cancer.Methods:This was a phase II, randomized, double-blind study. A total of 124 elderly patients (mean age, 75 yr; age range, 70–84 yr; 73% men) received V/G (n = 61) or placebo plus gemcitabine (n = 63). Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival, objective response rate, duration of response, disease control rate, time to deterioration of performance status, and safety outcomes.Results:PFS was significantly prolonged with V/G (median, 183 days; 95% confidence interval, 116–214) compared with placebo plus gemcitabine (median, 169 days; 95% confidence interval, 95–194; p = 0.047). No statistically significant differences between arms were observed in all secondary endpoints, including overall survival. The addition of vandetanib to gemcitabine was well tolerated. The rate of patients with ≥1 treatment-related adverse event was comparable in the two arms, pyrexia, dyspnea, and neutropenia being the most common adverse events.Conclusions:V/G combination was associated with a statistically significant prolongation of PFS compared with gemcitabine alone in untreated elderly patients with advanced non–small-cell lung cancer, with an acceptable safety profile

An analysis of the social and economic costs of breast cancer in Italy

Background: Breast cancer is the most prevalent cancer affecting women and it represents an important economic burden. The aim of this study was to estimate the socio-economic burden of breast cancer (BC) in Italy both from the National Health Service (NHS) and the government perspectives (costs borne by the social security system). Methods: The economic analysis was based on the costs incurred by the NHS from 2008 to 2016 (direct costs related to hospitalizations) and by the National Social Security Institute (INPS) from 2009 to 2015 (costs of social security benefits) for patients with breast cancer. The analysis was based on the Hospital Information System (HIS) and Disability Insurance Awards databases. For both databases, patients affected by a malignant neoplasm of the female breast, carcinoma in situ, or secondary malignant neoplasm of the breast were considered. Results: Results show that more than 75,000 women were hospitalized for breast cancer every year, with an overall cost for hospitalization of about €300 million per year. From the Social Security analysis, a number of 29,000 beneficiaries each year was estimated. Considering per patient social costs, breast cancer at the primary stage cost €8828 per year, while secondary neoplasms cost €9780, with an average total economic burden of €257 million per year. Conclusions: This analysis focused on the economic impact of breast cancer in Italy, showing that an advanced stage of the disease was associated with a higher cost

Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: An open-label, 2 × 2 factorial, randomised phase 3 trial

Background: Whether addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel (EC-P) is favourable in adjuvant treatment of patients with node-positive breast cancer is controversial, as is the benefit of increased density of dosing. We aimed to address these questions in terms of improvements in disease-free survival. METHODS: In this 2 × 2 factorial, open-label, phase 3 trial, we enrolled patients aged 18-70 years with operable, node positive, early-stage breast cancer from 81 Italian centres. Eligible patients were randomly allocated in a 1:1:1:1 ratio with a centralised, interactive online system to receive either dose-dense chemotherapy (administered intravenously every 2 weeks with pegfilgrastim support) with fluorouracil plus EC-P (FEC-P) or EC-P or to receive standard-interval chemotherapy (administered intravenously every 3 weeks) with FEC-P or EC-P. The primary study endpoint was disease-free survival, assessed with the Kaplan-Meier method in the intention-to-treat population. Our primary comparisons were between dose schedule (every 2 weeks vs every 3 weeks) and dose type (FEC-P vs EC-P). This study is registered with ClinicalTrials.gov, number NCT00433420. FINDINGS: Between April 24, 2003, and July 3, 2006, we recruited 2091 patients. 88 patients were enrolled in centres that only provided standard-intensity dosing. After a median follow-up of 7·0 years (interquartile range [IQR] 4·5-6·3), 140 (26%) of 545 patients given EC-P every 3 weeks, 157 (29%) of 544 patients given FEC-P every 3 weeks, 111 (22%) of 502 patients given EC-P every 2 weeks, and 113 (23%) of 500 patients given FEC-P every 2 weeks had a disease-free survival event. For the dose-density comparison, disease-free survival at 5 years was 81% (95% CI 79-84) in patients treated every 2 weeks and 76% (74-79) in patients treated every 3 weeks (HR 0·77, 95% CI 0·65-0·92; p=0·004); overall survival rates at 5 years were 94% (93-96) and 89% (87-91; HR 0·65, 0·51-0·84; p=0·001) and for the chemotherapy-type comparison, disease-free survival at 5 years was 78% (75-81) in the FEC-P groups and 79% (76-82) in the EC-P groups (HR 1·06, 0·89-1·25; p=0·561); overall survival rates at 5 years were 91% (89-93) and 92% (90-94; 1·16, 0·91-1·46; p=0·234). Compared with 3 week dosing, chemotherapy every 2 weeks was associated with increased rate of grade 3-4 of anaemia (14 [1·4%] of 988 patients vs two [0·2%] of 984 patients; p=0·002); transaminitis (19 [1·9%] vs four [0·4%]; p=0·001), and myalgias (31 [3·1%] vs 16 [1·6%]; p=0·019), and decreased rates of grade 3-4 neutropenia (147 [14·9%] vs 433 [44·0%]; p<0·0001). Addition of fluorouracil led to increased rates of grade 3-4 neutropenia (354 [34·5%] of 1025 patients on FEC-P vs 250 [24·2%] of 1032 patients on EC-P; p<0·0001), fever (nine [0·9%] vs two [0·2%]), nausea (47 [4·6%] vs 28 [2·7%]), and vomiting (32 [3·1%] vs 15 [1·4%]). INTERPRETATION: In patients with node-positive early breast cancer, dose-dense adjuvant chemotherapy improved disease-free survival compared with standard interval chemotherapy. Addition of fluorouracil to a sequential EC-P regimen was not associated with an improved disease-free survival outcome