Giovanni Bernardo

First-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain metastases from non-small-cell lung cancer: a phase II study.

On the basis of the hypothesis that responsiveness of brain metastases (BM) to chemotherapy is primarily determined by the chemosensitivity of primary tumor, rather than the ability of cytotoxic agents to penetrate the blood–brain barrier, we addressed the role of a new combination regimen with Vinorelbine (VNR), Gemcitabine (GEM), and Carboplatin (CBDCA) as a primary treatment modality in non-small-cell lung cancer (NSCLC) patients with BM. Twenty-two consecutive chemotherapy-naïve patients with documented BM from NSCLC and at least 1 evaluable extracerebral lesion were enrolled in this phase II study. Vinorelbine (25 mg/m2) and GEM (1000 mg/m2) were given on day 1, combined with a fixed daily dose of CBDCA at AUC=5.0 for three consecutive days. The cycle was repeated every three weeks in an outpatient setting. A total of 116 cycles was given (median 4, range 3–9 per patient). Specific evaluation of BM by contrast-enhanced computed tomography (CT) scan showed an overall response rate of 45% in 20 evaluable patients (95% confidence interval, 26–66%), with 3 (15%) complete and 6 (30%) partial remissions; in addition, three minor regressions, five disease stabilizations, and three progressions were found. Patients who responded for the brain also had a response at the extracerebral sites, and a benefit by a remission of symptoms and improvement of performance index was observed in 77% of the whole group. Median time to response was 10 weeks (range 6–12 weeks) and median response duration was 25 weeks (range 12–32 weeks). Median survival time was 33 weeks (range 18–62+weeks) in the whole group and 48 weeks in responders (range 26–62+weeks). The adopted schedule was well tolerated and easy to use in the outpatient setting, with good patient compliance. Our results, which are consistent with the study hypothesis, suggest that BM respond to chemotherapy in the same way as systemic disease and primary tumor, and further support the need for reconsideration of the role of chemotherapy in such a clinical setting. Controlled trials comparing chemotherapy with radiotherapy or concomitant sequential chemo-radiotherapy would be appropriate.

Intravenous or Oral Vinorelbine Plus Capecitabine As First-Line Treatment in HER2– Metastatic Breast Cancer: Joint Analysis of 2 Consecutive Prospective Phase II Trials

BACKGROUND The purpose of this study was to assess the activity and safety of the combination of vinorelbine (VNR) and capecitabine (CAP) as first-line treatment in HER2-negative (HER(-)) metastatic breast cancer (MBC). PATIENTS AND METHODS Patients (42) enrolled in trial A received intravenous (i.v.) VNR 25 mg/m2 on days 1 and 8 of a 21-day cycle combined with CAP 1000 mg/m2 twice daily for 14 consecutive days followed by 1 week of rest. Trial B (46 patients) followed trial A when the oral formulation of VNR became available at our institution. Patients received oral VNR (60 mg/m(2) on days 1-8) combined with the same CAP schedule as in trial A. RESULTS The response rate (RR) in trial A was 73.2% (95% confidence interval [CI], 56.4-82.8), including 12.2% complete responses (CRs). Clinical benefit was achieved in 78% of patients (95% CI, 63.2-87.9). In trial B, overall RR was 76% (95% CI, 62.0-86.0), with 13% CRs and clinical benefit of 80.4% (95% CI, 66.8-89.3). In trial A, median progression-free survival (PFS) was 8.2 months (range, 6-14+ months) and median overall survival (OS) was 32.4 months (range, 17-36+ months). In trial B, median PFS and OS were 8.8 months (range, 8-21+ months) and 34.3 months (14-39+ months), respectively. Treatment-related toxicity was manageable. Quality of life assessment showed a statistically significant difference regarding body image (p = .001), sexual functioning (p = .02), and future perspectives (p = .03) in women receiving chemotherapy fully by the oral route. CONCLUSION This joint analysis shows that both tested schedules can produce high objective RRs with encouraging PFS, manageable toxicity profile, and suggested benefit on some aspects of quality of life for the fully oral combination.

Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions

Accumulation of 99m Tc-Sn-pyrophosphate in pleural effusions has been evaluated in 56 patients grouped as follows: 8 with bacterial effusion (Group A), 27 with malignant effusion treated by local and/or parenteral antitumor chemotherapy (Group B), 21 with malignant effusion treated only by supportive therapy (Group C).Results, expressed as effusion to plasma PPi ratio, ranged from 0.1 to 0.28 in group A, from 0.04 to 0.64 in group B and from 0.60 to 1.73 in group C, with significant differences among the three groups. In no case was uptake found in cells of the sediment. Chemical analysis (including total and ionized calcium, total protein, acid and alkaline phosphatase) of plasma and exudate in neoplastic patients showed a slight, but significant, difference between groups B and C as regards plasma-effusion gradient for total calcium and acid phosphatase. Negative correlation also exists between effusion to plasma PPi ratio and plasma-exudate gradient for ionized calcium in neoplastic patients.The data support the hypothesis that acid phosphatase content and calcium gradient are among the factors involved in the mechanism of PPi accumulation in pleural effusions.

Multimodality treatment of unresectable hepatic metastases from pancreatic glucagonoma.

Glucagonomas are pancreatic islet cell tumors arising from the alpha cells which belong to neuroendocrine tumors. They frequently metastasize to the liver. We report the case of a 52- year old man with a pancreatic glucagonoma with synchronous multiple liver metastases treated by surgery, transarterial chemoembolization, percutaneous radiofrequency thermal ablation and long-acting octreotide. Our report confirms that a multimodal approach is very effective in patients with unresectable liver metastases from pancreatic endocrine tumors providing long-lasting palliation and probably prolonging survival.

Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

Treatment of Chronic Hepatitis C in a Patient Affected by Systemic Sclerosis

The currently recommended treatment for patients infected with hepatitis C virus (HCV) is pegilated interferon α (IFN α) plus ribavirin. Despite the numerous benefits of this therapy, there is an increasing concern regarding his tolerance. Among the most common side effects, interferon may trigger the onset or exacerbation of autoimmune diseases. When chronic hepatitis C coexists with an autoimmune disorder, it is not clear whether using interferon is better than avoiding it. We evaluated the disease state of a 55-year old female affected by sistemic sclerosis (SSc), during and after therapy with IFNα pegilated plus ribavirin for chronic HCV infection. We were worried about the potential worsening of the autoimmune disease during the therapy, but we were confident that we would give our patient a short course of peginterferon and ribavirin. A mild, asymptomatic worsening of lung SSc was observed during IFN administration, without life threatening symptoms. After 24 months follow up we observed the maintenance of the virological response and a good control of the rheumatological disease. Thus, in liver disease at high risk of progression and concomitant SSc, the antiviral therapy with IFNα is a feasible approach.

Trattamento loco regionale dell’epatocarcinoma non resecabile mediante chemioembolizzazione con microparticelle caricate con epirubicina: valutazione di efficacia, tollerabilità e analisi farmacocinetica in uno studio clinico monocentrico

Image-guided transcatheter arterial chemoembolization (TACE) is the first-line treatment for patients with intermediate stage HCC not candidate for curable therapies. Recently, microembolizing particles have been introduced in clinical practise; they are able to be loaded with chemotherapic agents, in particular doxorubicin, cisplatin and epirubicin. By now, two types of microparticles are mostly used in clinical practise: DC Bead® and HepaSphere Microsphere®. Drug Eluting Beads (DEBs)-TACE reduces side effects and improve local efficacy because the microparticles have a double effect: they embolize the arteries feeding the neoplastic lesion and they gradually realise the chemotherapic agent in the tumoral bed, to obtain high intratumoral drug levels and low systemic drug concentrations. The purpose of this study is to determine the prevalence of complication in patients affected by intermediate stage HCC treated with DEBs-TACE. Between January 2007 and December 2009, 80 patients have been treated with DEBs-TACE for a total of 125 treatments. Everyone was affected by intermediate stage HCC, mostly BCLC B; they received Drug Eluting Beads (DEBs)-TACE with DC Bead or HepaSphere MicroSphere pre-loaded with epirubicin (50 mg/vial). Biochemical blood analysis were performed before, 4 and 24 hours after the procedure to monitor some hematologic parameters. Side effects were reported following the Common Toxicity Criteria in order to evaluate post-TACE tossicity. Tumor response was assessed after 40 days from the procedure with CT scans according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). This study shows that the use of drug-eluting microspheres did not increase the risk of post-procedural complication and the prevalence of major adverse events are similar to conventional TACE, according to data reported in literature. We, also, noticed no differences in the prevalence of adverse events between patients treated with DC Bead-TACE and HepaSphereTACE. Moreover, in a selected group of 20 patients, 12 treated with DC Bead and 8 with HepaSphere, we performed peripheral blood samples analysis at the end of the embolic solution delivery and at 5, 10, 20, 40, 60, 120, 180, 360, 1,440 minutes after the procedure to assess epirubicin serum pharmacokinetic. The pharmacokinetic study showed low peak serum epirubicin concentrations as median peak level was 73.5+/-24.5 ng/mL for the DC Bead group and 33.9+/-11.0 ng/mL for the HepaSphere cohort. The highest drug concentration was observed after microspheres injection at 5 minutes in all 20 patients. The PK profile never dropped to zero up until the end of the experiment. In the time-interval included between 1 and 24 hours, persisting levels of epirubicin were detected in patients’peripheral blood samples, ranging from 2.3 to 24.2 ng/mL for both embolics. This study suggests that, after an earlier release effect, occurring during the very first few minutes, both microspheres are capable of a sustained kinetic release.

Analisi retrospettiva della prevalenza di complicanze correlate alle procedure di chemioembolizzazione intra-arteriosa epatica (TACE) nelle differenti classi di rischio

Transcatheter hepatic chemoembolization (TACE) is widely used in the treatment of unresectable hepatic tumors. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of complications and correlate them with some know risk factors. Between 2004 and 2009 we treated 155 patients (106 men and 49 women) with 297 sessions of TACE. 193 patients had primitive liver tumor and 104 had metastases from different primitivities. The patients were aged 49–86 years. TACE procedures were performed either with drug loaded microspheres (136 sessions with DCBead®; 124 with Hepasphere®) and with iodized oil (33 with Lipiodol®). The chemoterapeutic agent used was Epidoxorubicin in 217 sessions, Irinotecan in 30 and Oxaliplatin in 50. Our data showed that major complications occurred in 16.5% of patients. Specifically we found acute pancreatitis (2.7%), liver abscess (3%), cholecystistis (3.7%) and autoimmune thrombocytopenia (3.4%). Around 80 % of patients had postembolization syndrome that is not considered a complication but rather an expected outcome of embolotherapy. Complications occurred more frequently in diabetic than in non diabetic patients (26.7% vs 13.1%; p=0.006). Conversely we didn’t find any statistically significant differences according to the embolization agents used (Lipiodol® vs microspheres), the chemotherapic agent (Epidoxorubin vs Oxalplatin vs Irinotecan ), the age of the patients and the histology (primary vs metastatic tumors). All patients received antibiotic therapies before and after TACE; no statistically significant differences were found among the different classes of antibiotics used. Also no more complications were found with combined therapies (TACE+RFTA) than with TACE alone. Among the know risk factors only diabetes increases the prevalence of complications of TACE. TACE with Lipiodol® is more painful than drug loaded microspheres.

Unusual Complication of Percutaneous Radiofrequency Thermal Ablation of Hepatic Tumor: The Split Electrode

beneficial to our patient. If the emboli were composed of tumor cells, anticoagulation would not have prevented further embolization. Alternatively, if thrombus developed at the site of the tumor, providing another source of thromboembolism distinct from the popliteal vein aneurysm, anticoagulation may have been beneficial; however, this would have to be balanced against an increased risk of hemorrhage from the necrotic tumor center. In retrospect, it is arguable that earlier investigation of his liver as a possible source of emboli and cause of raised venous back pressure may have resulted in different management. However, with such an advanced hepatic malignancy, the prognosis would have been unchanged. In summary, we present a patient with long-standing hemochromatosis who had an incidental popliteal vein aneurysm and subsequently developed PE despite the absence of any peripheral deep venous thrombosis. The initial management did not include a complete study of the venous system or a search for hepatic tumor. Anticoagulation resulted in bleeding from a previously undiagnosed HCC, and further imaging demonstrated this to be causing IVC obstruction and also providing an alternative embolic source. Surgical treatment of the popliteal vein aneurysm would not have prevented further PE in this case. This case highlights the need to examine the entire venous system in patients with popliteal vein aneurysms and to search for all possible sources in those who present with PEs and also serves as a reminder that the diagnosis of HCC should always be considered in cases of hemochromatosis. Acknowledgment: We thank Vipin Uthappa, MD, for his help in providing images in this letter.