Vincenzo Bianco

New Approach for Modeling the Contribution of NSM FRP Strips for Shear Strengthening of RC Beams

This paper presents the main features of an analytical model recently developed to predict the near-surface mounted (NSM) fiber-reinforced polymer (FRP) strips shear strength contribution to a reinforced concrete (RC) beam throughout the beams loading process. It assumes that the possible failure modes that can affect the ultimate behavior of an NSM FRP strip comprise: loss of bond (debonding); concrete semiconical tensile fracture; mixed shallow-semicone-plus-debonding; and strip tensile fracture. That model was developed by fulfilling equilibrium, kinematic compatibility, and constitutive law of both the adhered materials and the bond between them. The debonding process of an NSM FRP strip to concrete was interpreted and closed-form equations were derived after proposing a new local bond stress-slip relationship. The model proposed also addressed complex phenomena such as the interaction between the force transferred to the surrounding concrete through bond stresses and concrete fracture as well as the interaction among adjacent strips. The main features of the proposed modeling strategy are shown along with the main underlying physical-mechanical concepts and assumptions. Using recent experimental data, the predictive performance of the model is assessed. The model is also applied to single out the influence of relevant parameters on the NSM technique effectiveness for the shear strengthening of RC beams.

Raltitrexed plus weekly oxaliplatin as first-line chemotherapy in metastatic colorectal cancer

AbstractAim: The primary aims of this study were activity and toxicity evaluation of a new raltitrexed and oxaliplatin-based regimen, as a first-line chemotherapy, in patients with metastatic colorectal cancer (MCC). Survival evaluation was considered a secondary endpoint. Patients and Methods: Forty-four patients were enrolled into this phase II trial. Treatment consisted of raltitrexed 3 mg/m2 iv on d 1 and oxaliplatin 70 mg/m2 iv on d 1 and d 8 every 3 wk. Results: Twenty patients (45.5%) achieved a response [95% confidence interval (CI): 30.1% to 54.1%], 18 (40.9%) had stable disease, and only 6 (13.6%) developed progressive disease. After a median follow-up time of 14.7 mo (range 6.3–18.6 mo), the median time to disease progression was 6 mo (range 2.0–16.7) (95% CI: 4.4–7.6) and the overall survival was 14.8 mo (range 3–23) (95% CI: 11.2–18.4). Neutropenia was the most common hematological side effect, while transient AST/ALT increase, neurotoxicity, asthenia, and diarrhea were the most common nonhematological side effects. Conclusions: Our data confirmed that oxaliplatin administered weekly plus raltitrexed is an active combination in newly diagnosed patients with advanced colorectal carcinoma that merits further investigation versus the classic schedule in a randomized, phase III trial.

Bevacizumab in ovarian cancer: A critical review of phase III studies

Bevacizumab (BV) is a humanized monoclonal antibody targeting vascular endothelial growth factor and it is the first molecular-targeted agent to be used for the treatment of ovarian cancer (OC). Randomized Phase III trials evaluated the combination of BV plus standard chemotherapy for first-line treatment of advanced OC and for platinum-sensitive and platinum-resistant recurrent OC. These trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, BV effectively improved the quality of life with regard to abdominal symptoms in recurrent OC patients. Bevacizumab is associated with adverse events such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed. This review describes the latest evidence for BV treatment of OC and selection of patients for personalized treatment.

Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer

The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41–0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.

Low-Dose Estramustine Phosphate and Concomitant Low-Dose Acetylsalicylic Acid in Heavily Pretreated Patients With Advanced Castration-Resistant Prostate Cancer.

BACKGROUND The aim of this phase 2 study was to evaluate the activity and tolerability of low-dose estramustine phosphate (EMP) with concomitant low-dose acetylsalicylic acid (ASA) as a thromboprophylactic agent in heavily pretreated patients with advanced castration-resistant prostate cancer. METHODS Patients received 420 mg of oral EMP twice daily and oral ASA 100 mg once daily. The primary endpoint was prostate-specific antigen response. All of the patients had been previously treated with docetaxel and abiraterone acetate, and 12 had also received cabazitaxel. RESULTS Thirty-one patients were enrolled. Prostate-specific antigen response was observed in 9 patients (29.0%; 95% confidence interval [CI], 14-48). Median progression-free survival was 3.6 months (95% CI, 2.2-5.6), and median overall survival was 7.6 months (95% CI, 6.9-9.7). Treatment was generally well tolerated, and no grade 3/4 toxicity was observed. Ten patients (32.2%) had grade 2 nausea and vomiting. No cardiovascular event and no major bleeding occurred. No venous thromboembolism event was observed. CONCLUSION Low-dose EMP with concomitant low-dose ASA seems to be a safe treatment option with some activity for patients with advanced castration-resistant prostate cancer who have been heavily pretreated.

Cisplatin, Etoposide, and Bevacizumab Regimen Followed by Oral Etoposide and Bevacizumab Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer: A Single-Institution Experience

UNLABELLED Cisplatin and etoposide (PE) is the most used chemotherapy regimen in extensive-stage disease small-cell lung cancer (ED-SCLC), and usually achieves a high initial response rate. An intriguing maintenance strategy could be the combination of the angiogenic agent bevacizumab (Bev) with a convenient and well tolerated chemotherapy agent such as oral etoposide. Results of the current single-institutional phase II study suggest that a regimen that includes conventional PE chemotherapy combined with Bev followed by oral etoposide and Bev as maintenance treatment is feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC. BACKGROUND In the present study we evaluated the efficacy and safety of a cisplatin (P), etoposide (E), and bevacizumab (Bev) regimen followed by maintenance oral E and Bev in patients with extensive-stage disease small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS Patients were administered 3-day fractionated P 25 mg/m(2) and E 100 mg/m(2) on days 1 to 3, every 3 weeks. After 3 PE cycles, all patients whose disease did not progress continued treatment with PE combined with Bev 15 mg/kg on day 3 every 3 weeks. After completion of 3 PE/Bev cycles, patients who did not experience tumor progression continued maintenance treatment with oral E 50 mg on days 1 to 14 every 21 days combined with Bev 3 times per week until occurrence of disease progression or unacceptable toxicity. RESULTS At our institution, 22 patients were enrolled and their median age was 66 years (range, 38-79 years). After completion of induction chemotherapy (3 PE cycles with 3 PE/Bev cycles) the objective response rate was in 17 patients (77.2%) (95% confidence interval [CI], 54.6-92.1). Twenty-one patients received maintenance treatment with oral E and Bev. The 9-month disease control rate was 8 patients (36.3%). Median progression-free survival was 7.8 months (95% CI, 7.0-11.3 months) and median overall survival was 13.2 months (95% CI, 11.8-18.7 months). Grade 3 to 4 neutropenia occurred in 12 patients (54.4%) and 14 patients (63.6%) of patients during cycles 1 to 3 and cycles 4 to 6 of induction chemotherapy, respectively. Severe adverse events during maintenance treatment were rarely observed. CONCLUSION A PE and Bev regimen followed by oral E and Bev maintenance treatment appears feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC.

Safety of sorafenib therapy in elderly adults with advanced hepatocellular carcinoma.

To the Editor: The incidence of hepatocellular carcinoma (HCC) is increasing worldwide and even more significantly with advancing age, reaching a peak at approximately age 75. Therefore, the proportion of elderly adults with HCC is expected to rise steadily in the coming years. Sorafenib represents the standard of care for individuals with advanced HCC, but data on the safety of this drug in elderly adults is lacking in the literature. Because a cancer treatment in older adults should be evaluated first in terms of tolerability and quality of life and only secondarily in terms of efficacy, it was decided to assess the safety of sorafenib-based therapy in elderly adults with advanced HCC. Therefore, a consecutive cohort of 51 individuals with advanced HCC aged 70 to 83, Child-Pugh A or B, and Eastern Cooperative Oncology Group performance status 0 to 2 who were not suitable candidates for or had progressed after locoregional therapies were retrospectively analyzed. Treatment with single-agent sorafenib at a standard dose of 400 mg was administered twice daily orally after informed consent was obtained. Therapy was continued until disease progression or unacceptable toxicity. Effect of treatment on quality of life and self-sufficiency were evaluated according to the instrumental activity of daily living (IADL) scale at baseline and every clinic visit. Adverse events were reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. Because the study population was composed of elderly individuals, comorbidities were frequent, with cardiovascular diseases being the most common (72.6%), with hypertension the most represented. The median duration of sorafenib treatment was 217.5 days (~7 months; range 1–48 months). Nonhematological toxicity was reported in all participants, mostly during the first month and of Grade 1 or 2 according to NCI CTCAE version 3.0 grading scale. The most common were hypertransaminasemia (74.5%), fatigue (64.7%), hand–foot syndrome (49.0%), hyperbilirubinemia (49.0%), diarrhea (47.1%), abdominal pain (41.2%), anorexia (29.4%), high blood pressure (11.7%), and nausea (9.8%). The most frequent Grade 3 adverse reactions were fatigue (15.7%), hand–foot syndrome (15.7%), abdominal pain (11.7%), and hyperbilirubinemia (11.7%). Of the six individuals with high blood pressure, who were receiving proper antihypertensive treatment before starting sorafenib, only one interrupted sorafenib therapy because of progressive disease and hypertensive crises; the antihypertensive therapy was modified according to the increases in blood pressure during sorafenib treatment in the remaining five. Hematological toxicity, commonly of Grade 1, was observed as thrombocytopenia in 60.7% of cases, of which 11.7% were Grade 3. No Grade 4 was reported (Table 1). Dose reduction (from 800 to 400 mg/d) due to toxicity was required in 28 individuals (54.9%), mainly because of thrombocytopenia (15.7%). Twenty-four individuals (47.1%) interrupted treatment, mostly because of fatigue (13.7%), thrombocytopenia (11.7%), and diarrhea (11.7%). Data obtained in other studies of sorafenib in elderly adults with cancer confirm these data. As reported in studies of older adults with renal cell carcinoma, those adverse events could be attributable to greater sensitivity of elderly adults than of younger individuals to the drug, although lower efficacy was not described in older adults. In the current study, the disease control rate, which was higher in the first 12 weeks than during the rest of the follow-up, was 45.1%, and partial response was achieved in five individuals over the first 12 weeks and in one individual over the first 24 weeks; furthermore, over the first 48 weeks, partial response was seen in one individual and complete response was obtained and maintained in two individuals for 5 and 4 years, respectively. Finally, stable disease was achieved during treatment in most individuals, as frequently reported in the literature. All participants showed good self-sufficiency (IADL score >5 in 68.6%, median at baseline 5.8 1.7). During treatment, IADL score decreased in 13 patients (25.5%). Mean IADL score was 5.5 2.2 at Day 30, 5.8 2.0 at Day 60, 5.9 1.8 at Day 90, 6.1 1.4 at day 120, and 6.1 1.3 at Day 150, indicating that the observed toxicity only modestly affected the quality of life and selfsufficiency of most participants.

Capecitabine in elderly patients with metastatic breast cancer

AIMS AND BACKGROUND Capecitabine is the reference treatment for anthracycline- and/or taxane-pretreated metastatic breast cancer (MBC). This study examined its efficacy, tolerability and impact on the quality of life of elderly patients with MBC. MATERIALS AND METHODS Between January 2002 and December 2009, 75 consecutive elderly patients with MBC received first-line chemotherapy with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks. Endpoints were efficacy, tolerability and clinical-benefit response measured every 3 cycles. RESULTS Median age was 76 years (range 65-88); median ECOG performance status was 1 (range 0-2); 51 patients (68%) had received adjuvant chemotherapy and all patients had received hormonal therapy. Median exposure was 6 cycles. After 3 cycles, 11 patients (14.7%) had a partial response, one patient experienced a complete response, and 49 patients (65.3%) had stable disease, amounting to a disease control rate of 81.3%. Stable disease was maintained in 45 patients (60%) after 6 cycles, in 21 patients (28%) after 9 cycles, and in 13 patients (17.3%) after 12 cycles. A clinical-benefit response was experienced by 42 patients (56%), indicating a positive impact on quality of life. Treatment was well tolerated, the most common grade 3 events being diarrhea (12%) hand-foot syndrome (8%), and mucositis (8%). Adverse events were managed with dose adjustments and supportive therapy when required. CONCLUSIONS Our results indicate that capecitabine is active and well tolerated in elderly patients with MBC. This dosing regimen warrants further study in the first-line setting for patients with less aggressive MBC who are not candidates for combination therapy.

Tolerability of single-agent sorafenib in the treatment of elderly patients with hepatocellular carcinoma (HCC).

We appreciate the valuable comments made by Dr. Lo. We agree that serum a-fetoprotein (AFP) levels sometime fluctuate during serial observations. Therefore, we used the average AFP integration value in our study, as previously described, and an AFP fluctuation that may have occurred during our observation period was not likely to affect the average AFP result. We also agree that a 1-month interval between AFP measurements for lowrisk patients is too frequent. In our study, the AFP measurement interval depended on an individual patient’s risk for hepatocellular carcinoma (HCC), and in accordance with the Japanese Evidencebased Clinical Guidelines for the Diagnosis and Treatment of HCC, our AFP measurement interval was every 6 months for low-risk patients. Unlike other cross-sectional studies that examined AFP values as a tumor marker to detect current HCC, our longitudinal cohort study determined the clinical significance of posttreatment AFP values and evaluated whether AFP values could be used as a predictive risk factor for “future” HCC development. We hypothesized that the AFP values during the observation period associate with the risk for “future” HCC development because elevated serum AFP is sometimes observed in patients with advanced chronic hepatitis C virus (CHC) in the absence of HCC. The positive predictive value of AFP was low. However, the extremely high negative predictive AFP value (0.960) suggested that the postinterferon (post-IFN) treatment AFP value <6.0 ng/mL predicted a decreased likelihood of “future” HCC development. In the HALT-C study, the AFP was 20 ng/mL in 50% of patients who developed HCC, suggesting that the AFP predictive criterion of 20 ng/mL is insufficient to predict a low risk for HCC development. Therefore, post-IFN treatment predictive AFP levels should be <6.0 ng/mL to suppress the risk for “future” HCC development. The HCC incidence is largely different between Western countries and Japan (Western< Japan). Therefore, future studies are needed to determine whether our results are in agreement with long-term, large cohort studies that include various population subgroups. Nevertheless, we believe that our results have important clinical implications for clinicians considering an individual patient’s HCC surveillance and/or treatment strategy. We also appreciate the valuable comments made by Drs. Toyoda, Kumada, and Tada. We are also aware that there are two distinct patterns of HCC development after sustained virological response (SVR) has been achieved. Although we carefully ruled out the existence of HCC by imaging modalities, we agree that the limit of detection of our imaging apparatus did not allow us to detect and completely exclude minute HCC. However, this raises the question as to whether incidences of minute HCC are capable of producing detectable AFP. We agree with Dr. Toyoda et al. that an AFP fucosylated fraction (AFP-L3) may be useful to address this question. Unfortunately, pre-IFN treatment AFP-L3 levels were not available in our patients who had post-IFN AFP 10 ng/ mL and developed HCC after achieving SVR (n 5 11). AFP-L3 values were available from nine patients at the time of HCC development and were 10% in eight (89%) patients, suggesting that AFP production was unlikely specific to HCC in these patients. In addition, AFP levels at the time of HCC development were not higher than AFP levels during follow-up for 8 out of 11 patients. Therefore, although the possibility of minute undetectable HCC before IFN treatment existed, elevated AFP was unlikely associated with preexisting HCC in patients with post-IFN AFP 10 ng/mL who had HCC after SVR was achieved.

Prevention of delayed emesis induced by moderately emetogenic chemotherapy in patients with acute emesis

The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients.During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy).In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as ≤ 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects.The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial.