A phase I dose-escalation study of Selumetinib in combination with Erlotinib or Temsirolimus in patients with advanced solid tumors.

Unlabelled: Background Combinations of molecularly targeted agents may provide optimal anti-tumor activity and improve clinical outcomes for patients with advanced cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. We investigated the safety, tolerability, and pharmacokinetics (PK) of selumetinib in combination with molecularly targeted drugs erlotinib or temsirolimus in patients with advanced solid tumors.

A phase I dose-escalation study of selumetinib in combination with docetaxel or dacarbazine in patients with advanced solid tumors.

Background: The RAS/RAF/MEK/ERK pathway is constitutively activated in many cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric MEK1/2 inhibitor with a short half-life that has shown clinical activity as monotherapy in phase I and II studies of advanced cancer. Preclinical data suggest that selumetinib may enhance the activity of chemotherapeutic agents.

Estimation of tumour regression and growth rates during treatment in patients with advanced prostate cancer: a retrospective analysis.

Background: We applied mathematical models to clinical trial data available at Project Data Sphere LLC (Cary, NC, USA), a non-profit universal access data-sharing warehouse. Our aim was to assess the rates of cancer growth and regression using the comparator groups of eight randomised clinical trials that enrolled patients with metastatic castration-resistant prostate cancer.

Methods: In this retrospective analysis, we used data from eight randomised clinical trials with metastatic castration-resistant prostate cancer to estimate the growth (g) and regression (d) rates of disease burden over time.

AZD1480: a phase I study of a novel JAK2 inhibitor in solid tumors.

Background: AZD1480 is a novel agent that inhibits Janus-associated kinases 1 and 2 (JAK1 and JAK2). The primary objective of this phase I study was to investigate the safety and tolerability of AZD1480 when administered as monotherapy to patients with solid tumors.

Methods: Thirty-eight patients with advanced malignancies were treated at doses of 10-70 mg once daily (QD) and 20-45 mg b.

Phase I/II multicenter study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD4877 in patients with refractory acute myeloid leukemia.

Eg5 (kinesin spindle protein) is a microtubule motor protein, essential for centrosome separation during mitosis. This Phase I/II, open-label, multicenter, two-part study investigated AZD4877, a potent Eg5 inhibitor, in patients with acute myeloid leukemia. Primary objectives were to determine the maximum tolerated dose (MTD) (part A), assess efficacy (part B) and determine the pharmacokinetic profile (parts A and B).

Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

Cancer fatigue: the way forward.

Research in cancer-related fatigue lags far behind research in cancer-related pain and is astonishingly underdeveloped given the magnitude of the problem among cancer patients. This was recently recognized at the State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue, held at the U.S.

Clinical trial design for target-based therapy.

Anticancer drug discovery has shifted from an empiric random screening directed approach to a more rational and mechanistic, target-based approach, which reflects our rapidly expanding knowledge of the pathogenesis of a variety of forms of cancer at the molecular level, providing new targets for drug discovery and development. The clinical development of target-based anticancer drugs will require fundamental changes to the traditional clinical trial design and end points that have been used for conventional cytotoxic drugs. In the phase I and II settings, traditional end points (toxicity and response) may not be suitable for more selective, cytostatic target-based agents, and these end points may be replaced by biological or pharmacokinetic end points to define the optimal doses and the therapeutic effects of these drugs on their targets.

Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors.

Purpose: To evaluate the proposed cancer-related fatigue (CRF) diagnostic criteria in a sample of cancer survivors. More accurate prevalence estimates of CRF may result in improved diagnosis and management of one of the most common symptoms associated with cancer and its treatment.

Methods: Three hundred seventy-nine individuals who had been treated with chemotherapy, either alone or in combination with radiation therapy, were surveyed.

[Fatigue syndrome caused by malignant tumor. An increasing priority in patient care].

As oncologists have become more effective in alleviating pain, nausea and depression, fatigue has emerged as the most important symptom suffered by cancer patients. Indeed, the current literature suggests that fatigue is currently the most important untreated symptom in cancer medicine. In recent surveys of patients and their caregivers, fatigue is more important for the quality of life than pain, nausea or depression.

Impact of fatigue on quality of life in oncology patients.

Fatigue is the most commonly reported symptom in cancer patients and has a profound effect on patient quality of life (QOL). The Fatigue-1 and Fatigue-2 surveys performed by the Fatigue Coalition have shown that fatigue occurs on a consistent basis in approximately three quarters of patients treated for cancer. Fatigue-2 study results show that fatigue is associated with significant physical, emotional, psychologic, and social consequences, with virtually every aspect of daily life being affected.

Use of complementary medicine by adult patients participating in HIV/AIDS clinical trials.

Objective: To identify and characterize patterns of use of complementary and alternative (CAM) therapies by human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients participating in clinical trials in a research setting.

Design: A descriptive survey using a nonrandom sample of 100 patients was conducted over 17 months, using a 99-item interview schedule adapted from a previous study.

Setting: National Institutes of Health (NIH) Warren G.

Impact of cancer-related fatigue on the lives of patients: new findings from the Fatigue Coalition.

Purpose: This survey was designed to confirm the prevalence and duration of fatigue in the cancer population and to assess its physical, mental, social, and economic impacts on the lives of patients and caregivers. Patients and Methods. A 25-minute telephone interview was completed with 379 cancer patients having a prior history of chemotherapy.

The impact of fatigue on patients with cancer: overview of FATIGUE 1 and 2.

Fatigue is a complex, multifactorial disorder with physical, mental, and psychological dimensions that has been associated with diminished quality of life (QOL) in patients with cancer. The prevalence and severity of fatigue, however, has only recently been studied systematically. Two national surveys commissioned by The Fatigue Coalition, a multidisciplinary group of medical practitioners, researchers, and patient advocates, whose mission is to study the importance of fatigue for patients with cancer and their caregivers, have assessed the prevalence, severity, and QOL consequences of fatigue in patients with cancer.

The Impact of Fatigue on Patients with Cancer: Overview of FATIGUE 1 and 2.

Fatigue is a complex, multifactorial disorder with physical, mental, and psychological dimensions that has been associated with diminished quality of life (QOL) in patients with cancer. The prevalence and severity of fatigue, however, has only recently been studied systematically. Two national surveys commissioned by The Fatigue Coalition, a multidisciplinary group of medical practitioners, researchers, and patient advocates, whose mission is to study the importance of fatigue for patients with cancer and their caregivers, have assessed the prevalence, severity, and QOL consequences of fatigue in patients with cancer.

Use of complementary medicine by adult patients participating in cancer clinical trials.

Purpose/objectives: To document the prevalence, demographic correlates, patterns of use, and beliefs about complementary and alternative medicine (CAM) therapies of adult patients enrolled in National Cancer Institute (NCI) clinical trials.

Design: Prospective, cross-sectional, descriptive survey.

Setting: W.

10th NCI-EORTC Symposium on New Drugs in Cancer Therapy: Dutch Treat Revisited.

Scientific meetings, like living organisms, tend to evolve over time. For example, the yearly ASCO meeting, which began as a small American academic oncology gathering emphasizing clinical research, has grown into a large, international forum which increasingly emphasizes best standard of care and reimbursement issues [Editor's note: see ASCO review by Chabner, Friedberg in this issue, page 263]. One meeting which has remained true to its initial mission is the NCI-EORTC Symposium on New Drugs in Cancer Therapy which occurs every two years in Amsterdam.