Prognostic significance of angiogenic factors in uterine cervical cancer.

BACKGROUND/AIM: Angiogenesis is pivotal in tumour development and progress, and targeted tumour therapies, such as bevacizumab, have shown promising results. However, in unselected patient populations, the treatment with angiogenesis-targeted combination regimens is marred by a variable response, non-negligible toxicity and questionable economy. The present study summarizes research to identify individual circulating angiogenic factors as markers for disease severity and possibly treatment response. PATIENTS AND METHODS: A total of 125 patients with cervical cancer from the ongoing cervical cancer monitoring database of the University Hospital Charité, Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age, HER2, HPV, smoking and menopausal status, and serum concentrations of vascular endothelial growth factor (VEGF), VEGF-D, VEGF-C, endoglin, endostatin, angiogenin, basic fibroblast growth factor (FGFb), vascular endothelial growth factor receptor (VEGF-R1), VEGF-R2, soluble inter-cellular adhesion molecule 1 (sICAM 1), soluble vascular adhesion molecule 1 (sVCAM 1), insulin-like growth factor 1 (IFG-1) and insulin like growth factor binding protein 3 (IGF-BP3). RESULTS: There was a clear association of angiogenic factor concentrations with stage of disease. Angiogenin showed an independent discrimination for cervical intraepithelial neoplasia (CIN) and invasive stages, and endoglin did so for invasive stages vs. recurrent disease. However, none of the potential markers under investigation was anywhere near selective enough to allow for a clinically meaningful prediction of prognosis or response. CONCLUSION: The association of circulating angiogenic factors with disease progression in cervical cancer is confirmed, but its utility for prognosis prediction and patient stratification for targeted therapies is doubtful.

Tumor-specific correlation of tumor M2 pyruvate kinase in pre-invasive, invasive and recurrent cervical cancer.

UNLABELLED: The aim of this study was to investigate the diagnostic value of tumor M2 pyrurate kinase (Tu-M2-PK) as a tumor marker in patients with pre-invasive (CIN), invasive (PCC) and recurrent (RCC) cervical cancer. MATERIALS AND METHODS: Plasma samples were investigated from 125 patients, comprising 50 cases of CIN (I-III), 51 of PCC (FIGO I-IV) and 24 of RCC, before treatment. Tu-M2-PK levels were determined by using a quantitative sandwich enzyme immunoassay. RESULTS: With the increase in disease severity from CIN to PCC to RCC, levels of Tu-M2-PK significantly increased (p<0.001). Levels of Tu-M2-PK significantly increased with respect to the FIGO stage (p<0.001) and had significantly higher values in node+ patients (p=0.028). There was no significant difference in Tu-M2-PK levels in CIN I-III patients (p=0.626). Patients with distant metastasis had significantly elevated levels of Tu-M2-PK (p<0.001). CONCLUSION: Tu-M2-PK can be used as a marker to differentiate between malignant and premalignant cervical lesions. In addition, the concentration of Tu-M2-PK correlates with the clinical stage of the disease.

Chemotherapy treatment options for elderly women with breast cancer.

Due to improved life expectancy and the increase in incidence of breast cancer in old age, ever more older women are developing this disease. Although there is only limited evidence-based data from randomized trials on the treatment, older patients are still under-represented in clinical studies, and currently there is no clear consensus on chemotherapy treatment for older women with breast cancer. Adjuvant therapy strategies, in particular, suffer from a lack of uniform standards and reflect a generally less aggressive treatment. Recently published studies have shown that older women suffering from breast cancer can also profit from a treatment based on therapeutic standards and consensus guidelines. In spite of developments in adjuvant chemotherapy using increased amounts of therapeutic agent to improve survival, many older patients receive instead reduced quantities of chemotherapeutic agent. Thus, the questions arise, whether undertreatment of older patients with breast cancer can lead to a poorer outcome or whether new therapy strategies (e.g., dose-intensive chemotherapy) can be used with older patients. A common reason for dose reductions is neutropenia, but studies have shown that it is manageable by using granulocyte colony-stimulating factors (G-CSFs). In this review, the current status of clinical research in the area of adjuvant treatment and the necessity for clinical studies that take into account the special therapeutic requirements of older women are discussed.

Postoperative therapy modalities for cervical carcinoma.

Currently, the standard therapy for cervical carcinoma of FIGO stage IIB following adequate radical surgery is simultaneous radiochemotherapy with a platinous chemotherapeutic agent. According to the current state of scientific knowledge, all patients of FIGO stages IIA-IB with at least one additional risk factor (adenocarcinoma, pN1, L1, V1, pT1b2) also benefit from adjuvant radiochemotherapy. Various studies have shown that it is possible to successfully carry out a platinous radiochemotherapy. However, one disadvantage is that a number of patients have to break off therapy because of treatment-related toxicities. It has also been proven that a low hemoglobin level during radiochemotherapy is a negative prognostic factor for overall survival. The data regarding a possible survival advantage following an increase in the hemoglobin content in the blood of cancer patients by erythropoietin administration is still contradictory. As a result, the administration of new cytostatics, platinous combination chemotherapies, sequential instead of simultaneous regimens and appropriate supportive therapies have to be taken into account. Several studies are currently being conducted into the effectiveness of such new therapies on both life expectancy and quality of life (e.g., Cervix-NOGGO-AGO-Uterus 7-study).

Changes in the circulating plasma levels of VEGF and VEGF-D after adjuvant chemotherapy in patients with breast cancer and 1 to 3 positive lymph nodes.

BACKGROUND: The goal of the present study was to investigate the changes in concentration of the important lymph-angiogenesis factors vascular endothelium-derived growth factor (VEGF) and VEGF-D under adjuvant chemotherapy. MATERIALS AND METHODS: The blood plasma of a total of 142 patients with breast carcinoma and with 1 to 3 affected lymph nodes was investigated, using the quantitative sandwich enzyme immunoassay technique, prior to and following chemotherapy, within the framework of a randomized phase III study: the patients received either conventional or dose-intensified chemotherapy. RESULTS: In general, there was a significant reduction in VEGF levels after chemotherapy only in patients with large tumors (T3) (p = 0.043). There was also an almost significant reduction in patients with an overexpression of c-erbB-2 (Dako Score +3, p = 0.052). In contrast, the clearest reduction in VEGF-D occurred in patients with a positive hormone receptor status (p = 0.04) or in patients with a low expression of c-erbB-2 (Dako Score +1, p = 0.05). A significant effect of chemotherapy on VEGF-D was determined only in patients who had a baseline level that was above the normal (conventionel treatment p = 0.005; dose-intensified treatment p = 0.004). CONCLUSION: Both VEGF and VEGF-D levels changed after chemotherapy, depending on the patient and tumor characteristics. With respect to changes in the plasma levels of VEGF and VEGF-D, there were no significant differences between dose-intensified and conventional chemotherapy.