Advocacy for clinical trials: do the Royal Colleges and State cancer councils play an appropriate role?

Background: Endorsement of clinical trials by prominent local or national organisations may help to promote public awareness of and enhance patient and doctor participation in randomised trials.

Method: A survey was undertaken of the specialist medical colleges of Australia, State and Territory cancer councils and national cancer organisations, inquiring about their formal position on patient participation in randomised clinical trials and any activities they undertake to promote clinical trial participation.

Results: Responses were received from 18 of 20 organisations surveyed.

Lessons learned from the Decision Board: a unique and evolving decision aid.

One session of the conference was devoted to the presentation of different types of decision aids. This paper reports the experience and lessons learned through the development and use of the Decision Board. This is a uniquely interactive decision aid administered by the clinician during the medical consultation.

Quantification of matrix metalloproteinase activity in plasma of patients enrolled in a BAY 12-9566 phase I study.

The expression of matrix metalloproteinases (MMPs) is often associated with invasiveness or grade of tumours. Increased blood levels of MMP proteins, including MMP-1, MMP-2, MMP-3 and MMP-9 have been detected in various types of cancers. With the exception of one study, MMPs in serum and plasma have been determined using ELISA.

A diffusion theory model of spatially resolved fluorescence from depth-dependent fluorophore concentrations.

A photon diffusion model has been developed to calculate the steady-state spatially resolved fluorescence from pencil beam excitation in layered tissue. The model allows the calculation of both the excitation reflectance and the fluorescence escape for an arbitrary continuous depth distribution of tissue optical properties and fluorophore concentration. The validity of this model was verified by comparison with Monte Carlo simulations and experimental measurements using phantoms with tissue-like optical properties.

Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials.

Purpose: Two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials were conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy (HCM).

Patients And Methods: Patients with moderate to severe HCM (corrected serum calcium [CSC] > or = 3.00 mmol/L [12.

A phase I dose escalation study of the matrix metalloproteinase inhibitor BAY 12-9566 administered orally in patients with advanced solid tumours.

Background: This phase I study was performed to evaluate the safety, tolerability, and efficacy of the oral matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced solid tumours, and to identify the maximum tolerated dose and dose for use in subsequent studies.

Patients And Methods: BAY 12-9566 was administered to 29 patients at doses ranging from 100 mg o.d.

Improving clinical practice guidelines for the 21st century. Attitudinal barriers and not technology are the main challenges.

Through the use of three scenarios, this paper presents the challenges for clinical practice guidelines in the 21st century. Such challenges relate to technological developments to improve the efficiency and pace of the development process, to ensure that clinical practice guidelines are kept up to date, and to facilitate implementation of guidelines in the clinical setting. To improve and ensure the validity of the content of clinical practice guidelines, we need to address the important problem of publication bias, for which researchers, granting agencies, industry, and journal editors share responsibility.

Scavenging of extracellular H2O2 by catalase inhibits the proliferation of HER-2/Neu-transformed rat-1 fibroblasts through the induction of a stress response.

High levels of reactive oxygen species (ROS) are associated with cytotoxicity. Alternatively, nontoxic levels of ROS like hydrogen peroxide (H(2)O(2)) can mediate the transmission of many intracellular signals, including those involved in growth and transformation. To identify pathways downstream of endogenous cellular H(2)O(2) production, the response of Rat-1 fibroblasts exhibiting differential HER-2/Neu receptor tyrosine kinase activity to removal of physiological H(2)O(2) concentrations was investigated.

Novel strategies for systemic treatment of endometrial cancer.

The median survival of women with advanced or recurrent endometrial cancer is less than one year. Of the women with early stage endometrial cancer and poor prognostic factors like high grade or deep myometrial invasion, 40% will recur. Over the last decade, incredible strides have been taken in evaluating systemic therapy for this disease, however, survival rates remain poor.

The multidimensional pain inventory profiles in patients with chronic cancer-related pain: an examination of generalizability.

This study examined the generalizability of the non-malignant pain patient profiles based on the Multidimensional Pain Inventory (MPI) to patients with cancer-related pain. Data were collected from 112 cancer patients. In total, 107/112 patients completed the MPI.

A comparison of elderly patients with aggressive histology lymphoma who were entered or not entered on to a randomized phase II trial.

The purpose of this study was to compare the baseline patient characteristics, treatments and outcomes of elderly patients with aggressive histology lymphoma who were entered or not entered onto a randomized phase II trial. We previously conducted a randomized phase II trial in patients > or = 65 years of age who had advanced stage intermediate grade lymphoma. A registry of all patients meeting the inclusion criteria for that trial was maintained.

The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomized trial. Ontario Clinical Oncology Group.

Background: The purpose of this study was to evaluate the effect of breast irradiation on quality of life, including cosmetic outcome, for patients enrolled in a clinical trial.

Methods: Between 1984 and 1989, a randomized trial was conducted in Ontario, Canada, in which women with lymph node negative breast carcinoma who had undergone lumpectomy and axillary lymph node dissection were randomized to either breast irradiation or no further treatment. A modified version of the Breast Cancer Chemotherapy Questionnaire (BCQ) was administered to women at baseline, 1 month (4 weeks), and 2 months (8 weeks) after randomization.

Endometrial cancer. Prevention, detection, management, and follow up.

Objective: To review risk factors for uterine cancer; to discuss strategies for detecting uterine cancer; to outline prognostic factors and treatment; and to review the role of follow up for patients who have completed primary therapy.

Quality Of Evidence: MEDLINE was searched from January 1996 to June 1998 using the terms endometrial neoplasms, estrogen replacement therapy, hormone replacement therapy, tamoxifen, and screening. Only English language articles were reviewed.

Human metastatic prostate PC3 cell lines degrade bone using matrix metalloproteinases.

Bone metastases are often associated with osteolysis and subsequent pathological fractures. To determine if metastatic human cancer cells can directly degrade non-mineralized and mineralized bone, we used prostate PC3 adenocarcinoma cell lines, which were originally established from skeletal metastases. We show that PC3 cells and their conditioned medium degraded non-mineralized, osteoid-like radiolabelled extracellular matrices from human Saos2 and U2OS osteoblast-like cells.

Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis.

Purpose: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted.

Use of an electron reflector to improve dose uniformity at the vertex during total skin electron therapy.

Purpose: The vertex of the scalp is always tangentially irradiated during total skin electron therapy (TSET). This study was conducted to determine the dose distribution at the vertex for a commonly used irradiation technique and to evaluate the use of an electron reflector, positioned above the head, as a means of improving the dose uniformity.

Methods And Materials: Phantoms, simulating the head of a patient, were irradiated using our standard procedure for TSET.

Influence of the proto-oncogene c-fos on cisplatin sensitivity.

Cisplatin resistance has been associated with overexpression of the c-fos gene in a human ovarian carcinoma cell line. To determine whether the correlation between c-fos overexpression and cisplatin resistance was limited to this cell line or was a more generalized phenomenon, we investigated cisplatin sensitivity in rat fibroblast cells that overexpressed the c-fos gene. The cisplatin Ic50 values for two different c-fos transfectants, CMVc-fos and L1-3c-fos, were 7.

Multitargeted antifolate LY231514 as first-line chemotherapy for patients with advanced non-small-cell lung cancer: A phase II study. National Cancer Institute of Canada Clinical Trials Group.

Purpose: To evaluate the efficacy and safety of the multitargeted antifolate LY231514 (MTA) in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC).

Patients And Methods: Patients with measurable, advanced NSCLC who had not received previous chemotherapy for advanced disease were considered for this study. Eligible patients who gave written informed consent initially received MTA 600 mg/m(2) intravenously (IV) for 10 minutes every 3 weeks.

In vivo resistance to photofrin-mediated photodynamic therapy in radiation-induced fibrosarcoma cells resistant to in vitro Photofrin-mediated photodynamic therapy.

The effects of Photofrin-mediated photodynamic therapy (PDT) on the in vitro cell survival and in vivo tumor growth of murine radiation-induced fibrosarcoma (RIF) cell tumors have been examined following in vivo PDT treatment of tumors. The response to in vivo PDT is examined in tumors derived from RIF-1 mouse fibrosarcoma cells and in tumors derived from RIF-8A cells, which show in vitro resistance to PDT. A significant reduction in tumor volume is observed over the first three days following in vivo PDT treatment of either 5 or 10 mg/ kg.

Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells.

Bone metastases are a common complication in prostate and breast cancer patients. It leads to extensive morbidity and eventually mortality. Matrix metalloproteinases (MMPs) are known to be involved in the metastatic process.

Changes in mitochondrial mass, membrane potential, and cellular adenosine triphosphate content during the cell cycle of human leukemic (HL-60) cells.

Oxidative phosphorylation within the inner mitochondrial membrane generates the majority of cellular adenosine triphosphate (ATP) required for normal physiological functions (including regulation of cell volume and solute concentration, maintenance of cellular architecture, and synthesis of essential macromolecules). Its efficient functioning depends on the maintenance of an electrochemical gradient and is tightly coupled to the energetic demands of the cell and/or tissue. Commitment to and completion of the cell division cycle are sensitive to changes in the availability of mitochondrially derived ATP, although the relationship between cell cycle and mitochondrial physiology is poorly understood.

Treatment of venous thromboembolism in cancer patients.

The occurrence of venous thromboembolism complicates the management of the patient with malignant disease because of the need for anticoagulant therapy. Cancer patients have an ongoing thrombotic stimulus due to the underlying cancer and its associated treatments, but are also considered to be at increased risk for anticoagulant-related bleeding. In recent years, the results of clinical trials have demonstrated the safety and efficacy of weight-adjusted subcutaneous low molecular weight heparin, administered at home, for patients with acute deep vein thrombosis.