Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer.

We examined the use of MGI-114 (6-hydroxymethyacylfulvene) for the treatment of patients with advanced colorectal carcinoma. Twenty-six patients were enrolled, with a median age of 60 years (range 41-75); 64% were male and all patients had a performance status of 0 or 1. We administered a dose of 11 mg/m2/d x 5 days every 4 weeks. With a median of two cycles (range 0-6) administered, no complete responses or partial responses were observed. Four patients had no change in disease (16%); 15 patients (57%) had progressive disease; seven patients were inevaluable (27%). Toxicity was evaluated in 25 of 26 patients. The main toxicities were hematologic, including granulocytopenia and thrombocytopenia. Neuropsychiatric adverse events included hallucination (7.7%), depression/anxiety (15.4%), and/or insomnia (19.2%). Given the lack of antitumor activity, further study of MGI-114 in colorectal cancer does not appear warranted.

Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries waiting to be "translated" into useful therapies and diagnostics. In addition to highlighting the major research advances over the past year, this report also identifies key barriers to accelerating the pace of cancer research and outlines ASCO's recommendations for overcoming them. Despite these and other challenges, there is much good news on the front lines of cancer research. This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States.

Medical and nursing education and training opportunities to improve survivorship care.

Improving the quality of care for cancer survivors is contingent on having physicians, nurses, and other professionals with adequate training in survivorship care. Previous literature has documented the deficiencies in existing formal education programs regarding the complex needs of this growing population. Continuing education programs and basic curricula need to incorporate the expanding body of knowledge regarding the physiologic and psychosocial sequelae of survivorship. This article reviews the current status of survivorship education and provides direction for essential content in future education. Topics such as prevention of secondary cancers, long-term complications, rehabilitation services, quality-of-life issues, pain and symptom management, and treatment of recurrent cancer are critical competencies of education that should then become routine care for cancer survivors.

Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients.

BACKGROUND: Isotretinoin (13-cis-retinoic acid) is a synthetic vitamin A derivative, or retinoid, widely used in the treatment of cystic acne. Preclinical and clinical studies of high-dose isotretinoin in patients with head and neck squamous cell cancer (HNSCC) have produced encouraging results. We conducted a phase III randomized trial of low-dose isotretinoin versus placebo in early-stage HNSCC patients to assess its effect on second primary tumor incidence and survival. METHODS: We randomly assigned 1190 patients who had been treated for stage I or II HNSCC to receive either low-dose isotretinoin (30 mg/day) or placebo for 3 years. The patients were monitored for up to 4 more years. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazards models were used for multivariable survival analysis. All statistical tests were two-sided. RESULTS: Isotretinoin did not statistically significantly reduce the rate of second primary tumors (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 0.83 to 1.35) or increase survival (HR = 1.03, 95% CI = 0.81 to 1.32) compared with placebo in patients with early-stage HNSCC. Current smokers had a higher rate of second primary tumors than that of never (HR = 1.64, 95% CI = 1.08 to 2.50) or former (HR = 1.32, 95% CI = 1.01 to 1.71) smokers. The hazard ratio of death from any cause for current smokers versus never smokers was 2.51 (95% CI = 1.54 to 4.10) and for current smokers versus former smokers was 1.60 (95% CI = 1.23 to 2.07). Major sites of second primary tumors (n = 261) included lung (31%), oral cavity (17%), larynx (8%), and pharynx (5%). CONCLUSIONS: Low-dose isotretinoin was not effective in reducing the rate of second primary tumors or death or smoking-related disease. Smoking statistically significantly increased the rate of second primary tumors and death. Ongoing trials are testing higher doses of isotretinoin as part of combination bioadjuvant therapeutic methods for patients with locally advanced HNSCC.

2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline.

PURPOSE: To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). UPDATE METHODOLOGY: The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. RECOMMENDATIONS: The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF.

Clinical Cancer Advances 2005: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the lives of so many. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report, and I hope you find it useful.

Ongoing care of patients after primary treatment for their cancer.

Nearly nine million people living in the United States have had a diagnosis of cancer. As the population ages, this number will increase. Most of these people will need follow-up care to deal with problems related to their cancer. Depending on the cancer, they may or may not benefit from surveillance to detect recurrence. Most will be more likely than average to develop a second primary cancer. Some will be genetically susceptible to another type of cancer. Many will have complications from their treatment that need attention. Also, their treatment may have altered certain physiologic functions. Finally, many will have suffered psychosocial difficulties either as a result of their cancer or its treatment. This article deals with these issues for the most commonly encountered cancers. Its major goal is to alert physicians to be aware of and help them to deal with these issues. Clearly, such an ambitious goal can only be partly achieved in a single journal article. Hopefully, the references included will allow physicians to proceed further if they wish.

The NCCN clinical practice guidelines in oncology: a primer for users.

Guidelines are becoming increasingly important as potential tools in improving clinical decision making. Because oncology practice encompasses a large number of tumors and their variants and because each tumor is characterized by heterogeneous presentations and clinical evolutions, an oncology guidelines program must be large in scope. Oncology practice is slowly moving toward evidence-based status, but guideline developers still must rely on less than perfect information to achieve this scope. By formalizing the consensus process, the NCCN program relies on the expertise of a broad range of cancer specialists to interpret the major clinical studies and apply their evaluative skills in assessing the relevance of these studies to clinical practice. In areas in which data are meager or contradictory, these experts are still charged with making recommendations if they believe their collective clinical experience points to a reasonable approach to disease management. It follows, therefore, that guidelines represent one of the most dynamic areas in medicine. The annual review process is designed to incorporate change as new evidence or innovative therapies become available. Therefore, the guidelines should be a true reflection of the state-of-the-art in oncology. The ultimate goal, as always, is improving care for the cancer patient.

What are the most important symptom targets when treating advanced cancer? A survey of providers in the National Comprehensive Cancer Network (NCCN).

We derived a set of brief, clinically relevant symptom indices for assessing symptomatic response to chemotherapy for advanced bladder, brain, breast, colorectal, head and neck, hepatobiliary/pancreas, lung, ovarian, and prostate cancers. Questions were extracted from a multidimensional cancer quality of life (QOL) measurement system, the Functional Assessment of Cancer Therapy (FACT). Surveys of disease-related symptoms were presented to expert physicians and nurses at 17 National Comprehensive Cancer Network (NCCN) member institutions. In a two-step procedure, each expert narrowed the list to no more than five of the very most important to attend to when assessing the value of drug treatment for advanced disease. Symptoms endorsed at a frequency greater than chance probability were retained for the nine symptom indices. The resulting NCCN/FACT symptom indices are comprised of 6-15 items, depending on disease. Fatigue, pain, nausea, weight loss, worry about worsening condition, and contentment with current QOL were consistently selected by experts as priority symptoms across tumor sites. These nine tumor-specific symptom indices indicate the most important clinician-rated targets of chemotherapy for many advanced cancers. These results await validation in patient populations and examination of the extent to which changes in symptomatology translate into meaningful improvement to the patient.