Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the XELBEVOCT study.

Background: We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset.

Methods: This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites.

Changes of bone turnover markers and serum PTH after night or morning administration of zoledronic acid in breast cancer patients with bone metastases.

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times.

Prognostic significance of disordered calcium metabolism in hormone-refractory prostate cancer patients with metastatic bone disease.

Bone metabolic disruption that occurs in bone metastatic prostate cancer could lead to disturbances of calcium metabolism. The prognostic role of either hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone-refractory bone metastatic prostate cancer patients. Serum calcium was measured in 192 patients.

Variations along the 24-hour cycle of circulating osteoprotegerin and soluble RANKL: a rhythmometric analysis.

Unlabelled: The variability of serum osteoprotegerin (OPG) and soluble RANKL (sRANKL) along the 24-h cycle was assessed in 20 healthy women. No rhythmic variations of serum OPG, sRANKL or sRANKL/OPG ratio were detected as a group phenomenon. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL.

Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study.

Elevated circulating chromogranin A (CgA) levels are found in neuroendocrine tumors (NETs), but the diagnostic usefulness of this marker is still debatable. To assess the role of CgA for the diagnosis of gastroenteropancreatic (GEP) NETs and the identification of metastatic patients, an Italian multicenter observational study has been performed. CgA was evaluated in 202 GEP NET patients by IRMA and ELISA.

Chromogranin A expression in patients with hormone naïve prostate cancer predicts the development of hormone refractory disease.

Purpose: We assessed chromogranin A as a tissue biomarker in prostate needle biopsies or as a plasma biomarker, a risk factor for hormone refractory prostate cancer.

Materials And Methods: A total of 211 patients with newly diagnosed prostate cancer treated with luteinizing hormone releasing hormone analogues constituted the study cohort. Univariate and multivariate Cox regression analyses were used to assess the predictive role of tissue and plasma chromogranin A expression.

Comparison between two commercially available chromogranin A assays in detecting neuroendocrine differentiation in prostate cancer and benign prostate hyperplasia.

Background: Chromogranin A (CgA) is the neuroendocrine (NE) marker most frequently employed in detecting NE differentiation in prostate cancer patients, either at the tissue level or in the general circulation.

Methods: We compared the two commercially CgA assay kits in detecting NE differentiation, in benign hyperplasia (BPH) or prostate cancer (PC) patients (pts). 170 pts with BPH, 107 with BPH+inflammation, and 136 PC pts entered the study.

The neuroendocrine phenotype in prostate cancer: basic and clinical aspects.

Most of the conventional adenocarcinomas of the prostate display focal neuroendocrine (NE) differentiation at diagnosis, usually revealed by immunohistochemistry as solitary or clusters of cells, in the context of predominantly exocrine tumors. Even though the biological and clinical significance of NE differentiation in prostate cancer is still to be elucidated, NE phenotype is emerging as an important factor in the prognosis, evolution and progression of prostate cancer. It seems to be particularly relevant in facilitating prostate cancer progression during the ordinary androgen-suppression therapy (LHRH-analogs +/- anti-androgens).

Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study.

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated.

Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease.

The presence of neuroendocrine (NE) differentiation in the context of predominantly exocrine prostate cancer may play a key role in androgen-independent tumor growth. The prognostic significance of plasma chromogranin A (CgA) was assessed in a series of consecutive prostate cancer patients with hormone-refractory disease. One hundred and eight patients with newly diagnosed hormone-refractory prostate cancer entered the study.

Metabolic effects of single-dose pamidronate administration in prostate cancer patients with bone metastases.

Background: Increased osteolysis usually accompanies sclerotic bone metastases from prostate cancer. This provides a rationale for the use of bisphosphonates to treat bone pain and prevent skeletal complications.

Methods: The fasting urinary levels of calcium, hydroxyproline (OHPRO), pyridinolines (PYD), deoxypyridinolines (DPYD), collagen cross-linked N-telopeptide (NTX) and the serum values of calcium, total alkaline phosphatase and relevant bone isoenzyme, bone gla protein (BGP), carboxy-telopeptide of type I collagen (ICTP) and parathyroid hormone (PTH) were determined at baseline and on the 15th, 30th, 60th and 90th days after single-dose (90 mg) pamidronate administration in 35 consecutive prostate cancer patients with bone metastases.

Circulating chromogranin A in the assessment of patients with neuroendocrine tumours. A single institution experience.

Background: Chromogranin A (CgA) is a secretory protein present in dense-core vesicles of neuroendocrine (NE) cells. Its ubiquitous presence in NE tissues makes it a suitable circulating marker of neoplasms of NE origin.

Patients And Methods: Plasma CgA was determined in 178 patients with NE tumors and in 36 patients with non-endocrine malignancies.

Potential clinical value of circulating chromogranin A in patients with prostate carcinoma.

Background: Neuroendocrine (NE) differentiation of prostate adenocarcinoma has received increasing attention in recent years as a result of possible implications for prognosis and therapy. The presence of NE tumor subpopulation can be gauged non invasively by measuring circulating levels of secretory products, primarily chromogranin A (CgA).

Methods: This article provides a review on published papers evaluating circulating CgA in prostate cancer patients.

Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients.

Background: The concept that neuroendocrine cells detected within prostate adenocarcinoma produce paracrine factors, that may exert a proliferative effect on exocrine prostate tumor cells, provides a rationale for the use of somatostatin analogs with the aim to counteract or delay the tumor progression. This study was designed to provide preliminary information on the effect of the administration of a long-acting somatostatin analog, lanreotide, on plasma levels of chromogranin A (CgA). Secondary aims were the evaluation of changes in circulating prostate-specific antigen (PSA) and insulin-like growth factor-1 (IGF-1).

Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline.

Purpose: We evaluated the incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease. We also assessed the predictive role of bone turnover markers determined at baseline.

Materials And Methods: A total of 112 patients were consecutively enrolled in our study from July 1990 to July 1998 and followed until death or the last followup.

Circulating neuroendocrine markers in patients with prostate carcinoma.

Background: Circulating neuroendocrine markers were measured in patients with prostate carcinoma (PC), prostatic intraepithelial neoplasia (PIN), and benign prostatic hypertrophy (BPH) with the goal to: 1) evaluate the differences in the expression of these markers in patients with benign, premalignant, and primary or metastatic PC; 2) evaluate their prognostic significance; 3) compare values in patients with hormone-naive and hormone-refractory disease; and 4) assess changes after androgen deprivation or chemotherapy.

Methods: Serum neuron specific enolase (NSE) (immunoradiometric assay) and plasma chromogranin A (CgA) (enzyme-linked immunoadsorbent assay) were evaluated in 141 patients with BPH, 54 patients with PIN, and 159 patients with PC; 119 patients were bearing hormone-naive disease and 40 were bearing hormone-refractory disease. CgA was monitored in 31 patients submitted to androgen deprivation and in 24 patients receiving chemotherapy.

Differential patterns of bone turnover in relation to bone pain and disease extent in bone in cancer patients with skeletal metastases.

Background: The alteration of the bone microenvironment as a consequence of skeletal metastases is poorly understood. The aim of this study was to search for patterns of bone markers in relation to primary tumor type, bone pain, and number of sites involved in patients with bone metastases.

Methods: We studied 323 patients with bone metastases from various primary malignancies.

Changes in free and free-to-total prostate specific antigen after androgen deprivation or chemotherapy in patients with advanced prostate cancer.

Purpose: To provide preliminary data on whether the diagnostic role of serum prostate specific antigen (PSA) in assessing the response to treatment is improved by concomitant free PSA evaluation both markers were evaluated in 42 patients with advanced prostate cancer who received hormonal therapy and 57 with hormone refractory disease who received chemotherapy.

Materials And Methods: PSA was assessed at baseline and every 3 months during treatment. Free PSA was assessed in stored serum samples obtained at baseline and at maximum PSA decrease.

Pamidronate administration improves the secondary hyperparathyroidism due to "Bone Hunger Syndrome" in a patient with osteoblastic metastases from prostate cancer.

Background: The so-called Bone Hunger Syndrome is a metabolic derangement that sometimes complicates the natural history of prostate cancer patients with osteoblastic bone metastases. An excessive bone formation leads to calcium entrapment in bone and the subsequent increase of parathyroid hormone (PTH) levels, in response to calcium demand. PTH elevation stimulates the osteoclasts in sites distant from those involving the tumor, leading to osteomalacia.

Comparison of assay of total and bone-specific alkaline phosphatase in the assessment of osteoblast activity in patients with metastatic bone disease.

The evaluation of response of osseous metastases to systemic treatments is often low as a consequence of the different radiologic appearances that make objective assessment not only difficult but sometimes impossible. Radiographic evidence of recalcification, the UICC criterion of response, is often evident for 6 months and sometimes may be delayed even more. This accounts for lower response rates in bone with respect to other metastatic sites in clinical trials.

Cohort study of association of risk of breast cancer with cyst type in women with gross cystic disease of the breast.

Objective: To assess correlation between type of breast cyst and risk of breast cancer in women with gross cystic disease of the breast.

Design: Cohort study of women with breast cysts aspirated between 1983 and 1993 who were followed up until December 1994 for occurrence of breast cancer.

Setting: Major cancer prevention centre.

Relationship between CA 15-3 serum levels and disease extent in predicting overall survival of breast cancer patients with newly diagnosed metastatic disease.

In order to study the relationship between circulating levels of CA 15-3 and the disease extent in predicting survival, we prospectively followed 312 breast cancer (BC) patients, from October 1988 to March 1995, from the time of first relapse. CA 15-3 values were assessed before treatment onset. Disease extent was defined as the percentage of liver or lung involvement and the number of bone segments positive at scintigraphy.