D. Pectasides

Docetaxel and Cisplatin With Granulocyte Colony-Stimulating Factor (G-CSF) Versus MVAC With G-CSF in Advanced Urothelial Carcinoma: A Multicenter, Randomized, Phase III Study From the Hellenic Cooperative Oncology Group

PURPOSE The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. PATIENTS AND METHODS Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. RESULT Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. CONCLUSION MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

BackgroundColorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma.MethodsWe studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters.ResultsHER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome.ConclusionHER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential.

Determination and biological relevance of serum cross-linked type I collagen N-telopeptide and bone-specific alkaline phosphatase in breast metastatic cancer.

Bone metastasis is a frequent complication of cancer disease. The metastatic spread of cancer to bone is common to many different malignancies, particularly breast (ca. 73%), prostate (ca. 68%) and lung (ca. 36%) cancers. Metastases to bone cause increased bone resorption both from direct effects of the tumor itself and thought osteoclastic activation. The diagnosis and follow-up of bone metastatic cancer patients usually relies on skeletal X-ray and bone scintigraphy. However, the development of biochemical markers, used as indicators of bone metabolism, provides data useful in the clinical practice. The most important markers for bone remodeling process, bone formation and resorption, are bone-specific alkaline phosphatase (BAP) and N-telopeptide of type I collagen (NTx), respectively. In this report, we applied two solid-phase immunoassays used for the determination of BAP and NTx in serum of breast cancer (BC) post-menopausal women with bone metastasis and healthy individuals. BAP level in patients was found to be 45.72 +/- 12.92 U/l, while the normal range for healthy individuals was 14.2 - 42.7 U/l. The respective level of serum NTx was 19.20 +/- 8.87 nM bone collagen equivalents (BCE) for patients and 15.9 +/- 3.8 nM BCE for healthy women. Correlation of the obtained data showed elevated levels for both markers indicating high rate of bone degradation in breast metastatic cancer.

Successful treatment of adult patients with idiopathic recurrent pericarditis with an interleukin-1 receptor antagonist (anakinra)

Idiopathic recurrent pericarditis (IRP) is observed in 10–30% of cases after a first episode of acute pericarditis, whereas a second recurrence appears in anevenhigher rate (~50%) [1,2]. Although severalmechanisms have been suggested to explain recurrence, most of them appear simply contributory. Today, there is increasing evidence that autoimmune and autoinflammatory pathways aremainly involved in its pathogenesis [3,4]. The optimal regimen for treating IRP has not been established [1]. Several medications either alone or in combination have been tested including nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin, colchicine, corticosteroids, and immunosuppressive agents. To date, the only available medication proved in randomized trials to decrease the recurrence rate is colchicine [2]. However, even with colchicine, a substantial proportion of patients experience recurrences [2]. Recently, Picco and et al. reported the successful use of an interleukin1β receptor antagonist anakinra in three children with resistant IRP [4]. Here, we present our experience in three adults with drug resistant or intolerant IRP. All patients were informed in detail regarding the management with anakinra and gave informed consent. Case#1: A 26-year-oldmale had suffered 8 episodes of IRP since 2004. He has received various regimens including NSAIDs, colchicine, steroids and azathioprine (Fig. 2A). In October 2006 treatment with prednisone was instituted but his symptoms recurred every time the dose was tapered below 15mg/day. Unfortunately, the patient developed steroidrelated complications including glaucoma, osteopenia and proximal myopathy of the lower extremities. In his latest admission inMarch 2010, the patient was started on anakinra (150 mg/day subcutaneously, SC) as monotherapy for 3 months and steroidswere tapered off. Administration of anakinrawas followed byan immediate and dramatic clinical response International Journal of Cardiology 160 (2012) 66–77

Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg-negative chronic hepatitis B patients under 4-year entecavir therapy

BACKGROUND & AIMS Serum HBsAg levels might represent an important predictor of sustained off-treatment response in HBeAg-negative chronic hepatitis B (CHB). We evaluated the changes of HBsAg and interferon-inducible protein 10 (IP10) serum levels in HBeAg-negative CHB patients treated with entecavir. METHODS 114 patients received entecavir for a median of 4.3 years. HBsAg levels were determined at baseline, 6 and 12 months and every year thereafter until year-4. IP10 levels were measured at baseline and annually until year-4 in 76 patients. RESULTS Virological remission rates were high (year-1: 94%, after year-2: 97-98%). Compared to baseline, HBsAg levels decreased by a median of 0.03, 0.13, 0.17, 0.22, and 0.32 log₁₀ IU/ml at 6 months and 1, 2, 3, and 4 years, respectively (p≤0.001 for all comparisons). The proportions of patients with HBsAg decline of ≥0.5 or ≥1 log₁₀ IU/ml were 9% or 6% at year-1 and 21% or 10% at the last visit. Median IP10 levels (pg/ml) did not change from baseline to year-1 or -2 (245 vs. 229 or 251), but increased at year-3 and -4 (275 and 323, p<0.030). HBsAg drop ≥0.5 log₁₀ was associated with baseline IP10 or IP10 >350 pg/ml (p≤0.002). HBsAg loss occurred in 4/114 (3.5%) patients or in 1/2, 3/21, and 0/91 patients with baseline HBsAg <100, 100-1000 and >1000 IU/ml, respectively (p<0.001). CONCLUSIONS In HBeAg-negative CHB patients, 4-year entecavir therapy decreases serum HBsAg levels, but the rate of decline is rather slow. Serum IP10 levels represent a promising predictor of HBsAg decline in this setting.

The Role of Neoadjuvant Chemotherapy in the Treatment of Advanced Ovarian Cancer

Primary cytoreductive surgery followed by chemotherapy represents the current standard treatment for patients with advanced ovarian cancer. Neoadjuvant chemotherapy followed by interval debulking surgery has been proposed as an alternative approach for the initial management of bulky ovarian cancer, aiming at the improvement of surgical efficiency and patients’ quality of life. According to the hitherto published studies, consisting mainly of retrospective observations, neoadjuvant chemotherapy followed by interval cytoreduction appears to improve the prognosis and quality of life in selected groups of patients. The survival outcome in these patients is similar to that of the conventional approach, or even better in some of the cases. Moreover, patients undergoing debulking surgery after having received neoadjuvant chemotherapy had a reduced perioperative morbidity compared to patients undergoing primary cytoreduction. Concurrently, neoadjuvant chemotherapy provides preoperative knowledge of tumor chemosensitivity, hence allowing the surgeon to choose appropriately aggressive treatment. However, until the results of prospective randomized trials become available, neoadjuvant chemotherapy followed by interval surgery should be applied only to individual cases and primarily in the context of clinical trials.

Gemcitabine (G) vs gemcitabine-carboplatin (GCB) for patients with advanced non-small cell lung cancer (NSCLC) and PS:2. A prospective randomized phase II study of the Hellenic Co-Operative Oncology Group

7058 Background: PS:2 is an independent negative prognostic factor for patients(pts) with NSCLC. Most of the information about prognosis, response, survival and treatment options was obtained from subset analysis of large trials. Single agent chemotherapy has been proven superior to best supportive care on survival or quality of life. Purpose was to evaluate prospectively if the combination chemotherapy GCb has superior efficacy compared to single agent G in pts with advanced NSCLC PS:2. Primary end-point was clinical benefit. METHODS Pts received either G: 1250 mg/m2 every 14 days (Arm A) or G: 1250 mg/m2 and Cb: 3AUC every 14 days (Arm B). Both treatments were given in cycles of 28 days. Four were the maximum number of cycles. 102 pts were enrolled. Ten pts were non -eligible. Baseline demographics were comparable for both groups. Median age was 73 and 70.5 for group A and B, male 83% and 72%, stage IV 64% and 72%, two disease sites 36% and 40.5% respectively. Relative dose intensity for G was 76% and 71% for arm A and B. For the clinical benefit, the following factors were evaluated: pain, cough, dyspnea, weight loss, appetite, weakness, nausea, vomiting and overall general feeling. RESULTS are summarized below. [Figure: see text] Conclusions: The combination GCb is not superior to G alone in terms of clinical benefit, TTP, m. survival and 1 -year survival. The combination causes more toxicity particularly neutropenia. No significant financial relationships to disclose.

Vinorelbine in Combination with Interleukin-2 as Second-Line Treatment in Patients with Metastatic Melanoma. A Phase II Study of the Hellenic Cooperative Oncology Group

Objectives: To evaluate the efficacy and toxicity of the combination of vinorelbine and interleukin (IL)-2 in patients with metastatic melanoma as second-line chemotherapy. Patients and Methods: Twenty-two patients with histologically confirmed stage IV melanoma previously treated with temozolomide-based chemotherapy—only one regimen of chemotherapy for disseminated disease was allowed—were treated with vinorelbine 30 mg/m2 on days 1 and 15 and IL-2 subcutaneous 9 × 106 once daily on days 2–6 and 16–19 every 4 weeks for maximum of six cycles. Results: From January 2000 to July 2001, 22 patients entered the study; the median age was 56 years. Among 20 evaluable patients there were 2 (9.1%) objective responses including 1 complete response and 1 partial response. Five (22.7%) had stabilization of their disease, and 13 (59.1%) progressed. The median time to progression (TTP) was 2.9 months and the median overall survival was 9.1 months. There was a significant difference in TTP in patients who responded or remained stable (median TTP 10.75 months) and those who progressed (median TTP 2.1 months) (p < 0.05). There was also a difference in survival in the two groups (p < 0.05 (28 vs. 8 months). The most common side effects were flulike symptoms, such as fever, chills, fatigue, and injection site reaction. Grade 3 hematological toxicity rarely occurred. One patient discontinued therapy because of fatigue and anorexia. There were no treatment-related deaths. Conclusions: The combination of vinorelbine and IL-2 provides clinical benefit in patients recurring or progressing on first-line chemotherapy for metastatic melanoma, with manageable toxicity.

Su1804 Is Caffeine Responsible for the Hepatoprotective Effect of Coffee Consumption in Patients With Chronic Liver Diseases? A Multicentre Study

Which Factors Influence the Accuracy of Liver Stiffness Measurements by Transient Elastography (TE) and by Acoustic Radiation Force Impulse (ARFI) Elastography for Liver Fibrosis Evaluation? The Analysis of a Large International Cohort of Patients Simona Bota, Ioan Sporea, Markus Peck-Radosavljevic, Roxana Sirli, Hidetsugu Saito, Hirotoshi Ebinuma, Monica Platon Lupsor, Radu I. Badea, Mireen Friedrich-Rust, Christoph Sarrazin, Fabio Piscaglia, Sara Marinelli, Petra Salzl, Alina Popescu, Mirela Danila

The Management of Stage I Nonseminomatous Testicular Germ Cell Tumors

Testicular germ cell tumors represent the most common malignancies in young males; 70% of patients with seminomas and 50% of those with nonseminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis. Lymphovascular invasion, embryonal-cell carcinoma component, absence of yolk sac histology and MIB1 proliferation rate represent predictors of micrometastatic diseasein stage I NSGCT. Therapeutic options following orchiectomy in patients with stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection, surveillance or adjuvant cisplatin-based chemotherapy. All available treatment modalities produce excellent results, with a long-term survival of almost 100%. Consequently, therapy-induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile as well as the patient’s preferences and their ability to comply with each one of the modalities is the key to the management of stage I testicular cancer.