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Andrea Mancuso

Publications and source records attributed to Andrea Mancuso.

At least 19 recordsLinked to original sources
PubMed2006

Effective chemotherapy for hormone-refractory prostate cancer (HRPC): present status and perspectives with taxane-based treatments.

Prostate cancer is a significant health concern for men worldwide. It continues to be the most common lethal malignancy diagnosed in American men and the second leading cause of male cancer mortality. Hormone-refractory prostate cancer (HRPC) remains clinically challenging. Two large phase III studies have demonstrated a survival advantage in HRPC patients utilizing docetaxel chemotherapy, setting a new standard of care for this disease. This paper examines the progress that has been made in HRPC with the Taxanes (Docetaxel, Paclitaxel, and Epothilones) with a glimpse on mechanisms of resistance and on combinations able to overcome it. In addition, new targeted therapies under development in combination with taxanes are reviewed with an explanation of their molecular mechanisms of action.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Current therapies and advances in the treatment of pancreatic cancer.

Pancreatic cancer is a common, highly lethal disease with a rising incidence. In the last years continued efforts in pancreatic cancer research have led to a change in the classic approaches and to the development of new biological agents that appear to show promise. Adjuvant chemotherapy with gemcitabine has recently demonstrated better survival outcomes following surgical resection compared to no treatment, especially in patients with positive margins or lymph nodes. The addition of anti-VEGF agents to adjuvant regimens could improve long-term outcomes. In locally advanced disease, neoadjuvant regimens have not produced complete remissions, but partial responses have been reported ranging between 10 and 20%, with conflicting survival results. Combination trials with radiochemotherapy and new drugs appear well tolerated with encouraging preliminary results. In the metastatic setting, novel chemotherapeutic combinations and molecular targeted agents have shown promise in improving outcomes. To date, second line therapy is increasingly proposed and may even provide survival benefits in the future. This article summarizes the current standards of therapy for patients with resectable, advanced and metastatic pancreatic cancer.

Antimetabolites, Antineoplastic↗
PubMed2006

A prospective study of hepatocellular carcinoma incidence in thalassemia.

Hepatocellular carcinoma (HCC) is a complication of cirrhosis. Due to blood transfusions, patients with beta-thalassemia (thal) are often infected with either hepatitis C virus (HCV) or hepatitis B virus (HBV). In the past, many patients did not survive long enough to develop HCC. The recent improvements in prognosis have helped in the diagnosis of HCC that has developed. The aim of this study was to evaluate HCC incidence in beta-thal. We performed liver ultrasound (US) on all adults without a previous diagnosis of HCC. Risk factors (iron overload, HCV infection, HBV infection, cirrhosis) were evaluated. One hundred and eight thalassemia patients have been evaluated; of whom three were excluded (two patients as they were under the age of 18 years and one patient because he had a previous history of HCC). Seventy-two patients [31 had thalassemia major (TM), 41 had thalassemia intermedia (TI)] with risk factors (iron overload in 72, HCV infection in 46, HBV infection in two, cirrhosis in 10) and 33 (four with TM and 29 with TI) without risk factors underwent liver US. Overall, two patients were found to have a newly developed HCC. Of these two patients, one was treated with surgery and the other with percutaneous radiofrequency. Further follow-up did not show any evidence of recurrence after 23 and 15 months, respectively. Ultrasound screening can allow early detection and treatment of HCC in thalassemia patients.

Adolescent↗
PubMed2006

New treatment approaches in metastatic renal cell carcinoma.

PURPOSE OF REVIEW: Recent developments in the understanding of the molecular biology of renal cell carcinoma have led to the development of several biologic agents with different mechanisms of action. In 2005, promising results have been observed especially in second-line therapy following cytokine failures and in 2006 more mature data with regard to time to progression and overall survival should be available. This review, analyzing basic translational research principles, will summarize the available evidence with a glimpse of the future therapeutic approaches in renal cell carcinoma. RECENT FINDINGS: Vascular endothelial growth factor- and platelet-derived growth factor receptor-inhibiting drugs (SU11248, Bay 43-9006, Bevacizumab, AG-013736, etc.) report time to progression ranging between 4 and 9 months and variable benefits in overall survival. Confirmatory studies are ongoing regarding other novel treatments (CCI-779, Infliximab, PTK-787). SUMMARY: In renal cell carcinoma, there is a strong rationale for targeting multiple pathways and particularly angiogenesis. Vascular endothelial growth factor- and platelet-derived growth factor receptor-inhibiting drugs have been rapidly approved in the second-line setting and will soon be used as first-line therapy. In the next years, translational/clinical research will provide evidence for combination strategies to improve upon the results of the biologic agents and hopefully offer more hope to patients with renal cell carcinoma.

Angiogenesis Inhibitors↗
PubMed2005

Colorectal cancer and antiangiogenic therapy: what can be expected in clinical practice?

Angiogenesis is a strongly regulated process, which is dependent upon a complex interplay between inhibitory and stimulatory angiogenic factors. It is essential for tumor growth and metastasis: increased angiogenesis is correlated with poor prognosis in cancer patients. Many novel compounds that potently inhibit formation of neoplastic blood vessels have been recently developed. Major categories of angiogenesis antagonists include protease inhibitors, direct inhibitors of endothelial cell proliferation and migration, angiogenic growth factor suppressors, inhibitors of endothelial-specific integrin/survival signalling, copper chelators, and inhibitors with other specific mechanisms. There is increasing interest in developing angio-suppressive agents for colorectal cancer treatment. Some 20 direct and indirect antiangiogenesis drugs are currently being evaluated in clinical trials in colorectal cancer (CRC). Promising results have been reported. These include an increase in overall survival and reduction in the risk of death (Bevacizumab), reversal of cellular resistance (Cetuximab) and activity as second-line therapy in patients who have exhausted other available treatment options (Cetuximab, ABX-EGF, PTK-787, Gefitinib, Erlotinib). This review will outline the mechanisms of action of the principal antiangiogenic drugs, summarize the available data on the use of these new drugs in colorectal cancer, discuss their impact in clinical practice and offer a glimpse into how antiangiogenetic therapy will be integrated into the future care of patients with gastrointestinal cancers.

Angiogenesis Inhibitors↗
PubMed2005

New treatments for metastatic kidney cancer.

Renal cell carcinoma accounts for approximately 3% of adult malignancies and 90%-95% of neoplasms arising from the kidney. It is characterized by a lack of early warning signs, diverse clinical manifestations, resistance to radiation and chemotherapy, and infrequent but reproducible responses to immunotherapy with agents such as interferon alpha (IFNa) and interleukin 2 (IL-2). International studies have shown objective response rates of < 15% in patients with advanced and metastatic disease, with 5-year disease-specific survival ranging between 0-20%. Considering these poor outcomes, renal cancers' very vascular nature and overexpression of receptors for vascular endothelial growth factor (VEGF), various biologic and angio-suppressive therapies are being evaluated in clinical trials. Promising results in terms of overall response rate and median time to progression have been reported especially as second-line therapy following cytokine failure, a setting where no effective systemic therapy has been recognized (SU011248, Bay 43-9006, Bevacizumab and Erlotinib). While confirmatory studies are ongoing, other novel treatments in first line trials (CCI-779, Infliximab, PTK-787, and Thalidomide) have drawn international attention. This review, analyzing basic translational research principles, will summarize the available data on the use of these new therapeutic approaches in RCC.

Adult↗
PubMed2004

A new induction schedule of epoetin alfa 40.000 IU in anemic patients with advanced lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) treatment with new drugs in combination with platinum salts induce anemia G1/2 and G3/4 WHO in about 35 and 10-20% of patients, respectively, with a chemotherapy (CT) dose intensity decrease in 20% of cases. Epoetin alfa, administered at standard dosages has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy. OBJECTIVE: This open-label, non-randomized study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa 40.000 IU in lung cancer patients with moderate or severe anemia who were receiving CT. PATIENTS AND METHODS: Twenty-four patients (8 SCLC and 16 NSCLC) were enrolled in the study to receive single subcutaneous (s.c.) injections of epoetin alfa 40.000 IU on days 1, 4, 7, 10, and 13, followed by standard treatment (10.000 IU t.i.w.) for the further 2 weeks. Nine patients had been previously treated with epoetin alfa 10.000 IU t.i.w. Twenty-two patients were receiving first-line CT and two patients were receiving docetaxel as second-line CT. RESULTS: After 15 days of treatment, in 21 evaluable patients, Hb was 10.5 +/- 1.3 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.0 g/dL (95%CI: 1.3-2.7). Hb increase was > or =2g/dL in 11 patients, 1-1.9 g/dL in 5 patients, and <1g/dL in 5 patients. After 30 days of treatment, Hb was 11.5 +/- 0.8 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.9 g/dL (95%CI: 2.4-3.4) in 20 evaluable patients. No adverse events possibly related to epoetin alfa treatment were observed. CONCLUSION: An induction therapy with epoetin alfa 40.000 IU for 2 weeks followed by standard treatment allows an Hb increase of 2.9 g/dL even in advanced lung cancer patients with a moderate/severe anemia, without RBC transfusion requirements. A randomized study of the proposed induction dose of epoetin alfa 40.000 IU is actually ongoing.

Aged↗
PubMed2004

Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy.

BACKGROUND: Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.Objective. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy. METHODS: Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study. RESULTS: Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups. CONCLUSIONS: Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.

Adult↗
PubMed2003

TIPS for acute and chronic Budd-Chiari syndrome: a single-centre experience.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a technically challenging but feasible treatment for Budd-Chiari syndrome (BCS). However, information about the outcome, particularly in patients with liver failure, is scarce. We report our experience of TIPS for BCS. METHODS: Fifteen patients with BCS underwent TIPS. Eight had hepatic failure and seven underwent TIPS for BCS uncontrolled by medical treatment. RESULTS: Fourteen out of 15 had successful TIPS placement. Out of the eight hepatic failure patients, four died soon after TIPS: one liver rupture, one portal vein rupture, one liver failure and one pulmonary oedema. Another patient had a significant intrahepatic haematoma, which resolved with conservative management. TIPS was successfully placed in all of the seven patients with chronic BCS, in whom there was an average follow-up of 20 months. Ascites resolved and liver function improved in all. One patient died after 18 months from the original hepatic metastatic disease. Four patients have had evidence of TIPS dysfunction requiring three balloon dilatations and one restenting. No patient has required liver transplantation. CONCLUSIONS: TIPS should be the first line treatment for BCS uncontrolled by medical therapy. However, mortality in BCS with hepatic failure is high and liver transplantation could be a better option.

Adult↗
PubMed2003

Assessment of blood coagulation in severe liver disease using thromboelastography: use of citrate storage versus native blood.

Thromboelastography evaluates the viscoelastic properties of blood coagulation. Using native blood, measurement must start soon after sampling. With normal coagulation, native and citrated blood values correlate well. No data exists from cirrhotic patients. We compared native and citrate thromboelastography parameters in 30 cirrhotic patients (20 Child-Pugh C class, two liver failure). Thromboelastography was performed within 4 min using native blood and after recalcification within 1-2 h of citrate storage. Thromboelastography variables (, alpha, ) were compared using the Mann-Whitney test, correlation investigated with the Pearson method and the degree of agreement with the Bland-Altman method. There was no significant difference between citrated and native blood for all variables. Median values for native and citrated were, respectively, 16.4 (range 2.3-22.5) and 15.1 (range 9.8-29.9); 6.3 (range 3.5-11.3) and 6.2 (range 2.8-10.9); 48.3 (range 30.7-62.9) and 46.2 (range 30.4-60.4); angle alpha 30.8 (range 18.7-46.8) and 33.2 (range 19.9-55.8). Correlation for each variable was significant ( 0.01). There was a good degree of agreement for all but two patients (both bleeding) for all variables. Citrated blood can substitute native blood using thromboelastography in cirrhotic patients, allowing more time between sampling and the thromboelastography measurement.

Adult↗
PubMedDate not supplied

Atrial fibrillation during adjuvant chemotherapy with docetaxel: a case report.

A 46-year-old woman had an episode of atrial fibrillation during infusion of docetaxel as adjuvant chemotherapy for an infiltrating ductal carcinoma of the breast. All cardiological tests performed before treatment were normal and there was no evidence of thyroid dysfunction nor any objective or anamnestic data indicating acute or chronic cardiovascular disease. None of the drugs administered has ever shown any proarrhythmic activity. In controlled clinical trials docetaxel was found to have a very low cardiotoxicity.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer.

BACKGROUND: Oxaliplatin, a new DACH-platinum compound, has provided high response rates both in untreated and 5-FU-resistant patients. AIM: To define the feasibility and toxicity profile of Oxaliplatin administered as a continuous hepatic aterial infusion. PATIENTS AND METHODS: Seventeen patients with pretreated metastatic liver colorectal cancer were treated with Oxaliplatin 20 mg/m2/day by HACI x 5 days every 3 weeks. RESULTS: Toxicity grade 3 included pain (4 out of 17), asthenia (1 out of 17) and nausea (1 out of 17). Abdominal pain grade 4 (WHO) was noted in only one patient. Overall, severe abdominal pain (main dose-limiting toxicity) was observed in 41% of patients and no chemical hepatitis and sclerosing cholangitis pain-related was proven by an endoscopic retrograde cholangiography. The response rate was not a primary end-point; nonetheless among 15 evaluable patients we observed partial responses (PR) in 7 patients (46%) and stable disease (SD) in 21% of cases for an overall tumor growth control of 67%. Progression to disease (PD) was 33%. Following chemotherapy, one patient underwent surgical removal of residual metastases, with curative intent. The 1-year survival rate was 64%. The median duration of survival was 19 months. The median delay to hepatic progression was 10 months. CONCLUSION: Further studies are required to define the role of HACI Oxaliplatin, the schedule of administration (bolus vs continuous infusion) and the combination, also in this setting, with fluoropyrimidines.

Aged↗
PubMedDate not supplied

Weekly paclitaxel and 5-fluorouracil in pretreated patients with metastatic breast cancer: a phase I study.

BACKGROUND: Recent studies have shown a good activity/tolerability for weekly paclitaxel and 5-fluorouracil in protracted continuous infusion (p.c.i.) in metastatic breast cancer patients pretreated with anthracyclines. MATERIALS AND METHODS: To define the MTD of weekly paclitaxel (days 1-8-15-22, every 4 weeks with a starting dose of 75 mg/m2 and subsequent dose escalation: 90 mg/m2 and 105 mg/m2) in combination with a fixed dose of 5-fluorouracil in p.c.i. (250 mg/m2/day for 3 weeks + 1 week of rest). RESULTS: Eleven patients were enrolled; on Step III two patients experienced DLT (1 G 3 mucositis and 1 febrile neutropenia). G 3-4 toxicities were: G 3 mucositis (2 out of 11), G 3-4 neutropenia (1 out of 11). CONCLUSION: The recommended schedule for phase II studies is: paclitaxel 90 mg/m2/w + 5-fluorouracil 250 mg/m2 in p.c.i. for 21 days. This is the first phase I trial with the combination of weekly paclitaxel and 5-fluorouracil p.c.i. in advanced breast cancer patients.

Aged↗