Precision medicine clinical trials: defining new treatment strategies.

OBJECTIVES: To discuss the role of clinical trials in the changing landscape of cancer care resulting in individualized cancer treatment plans including a discussion of several innovative randomized studies designed to evaluate multiple targeted therapies in molecularly defined subsets of individuals. DATA SOURCES: Medical and nursing literature, research articles, and clinicaltrials.gov. CONCLUSION: Recent advancements in cancer biomarkers and biomedical technology have begun to transform fundamentals of cancer therapeutics and clinical trials through innovative adaptive trial designs. The goal of these studies is to learn not only if a drug is safe and effective but also how it is best delivered and who will derive the most benefit. IMPLICATIONS FOR NURSING PRACTICE: Implementation of clinical trials in the cancer biomarker era requires knowledge, skills, and expertise related to the use of biomarkers and molecularly defined processes underlying a malignancy, as well as an understanding of associated ethical, legal, and social issues to provide competent, safe, and effective health care and patient communication.

A web-based screening and accrual strategy for a cancer prevention clinical trial in healthy smokers.

Screening and recruitment of qualified subjects for clinical trials is an essential component of translational research, and it can be quite challenging if the most efficient recruitment method is not utilized. In this report, we describe a successful web-based screening and accrual method used in a randomized prospective chemoprevention clinical trial with urinary biomarker endpoints. The targeted study population was a group of at-risk healthy current smokers with no evidence of lung disease. Craigslist was used as the sole recruitment modality for this study. All interested subjects were directed to a pre-screening website, in which subject questionnaire responses were linked to the study coordinator's secure e-mail account. Of the 429 initial inquiries, 189 individuals were initially eligible based on the questionnaire response. One hundred twenty-two people were telephone-screened, of whom 98 subjects were consented, 84 were randomized and 77 subjects completed the study successfully. Utilizing this single web-based advertising strategy, accrual for the trial was completed 7 months prior to the projected date. Craigslist is a cost effective and efficient web-based resource that can be utilized in accruing subjects to some chemoprevention trials.

Biomarkers as molecular targets of drug interventions.

OBJECTIVES: To present an overview of biomarkers used in a multiplicity of roles, including as targets of therapeutic intervention for several organ sites. DATA SOURCES: Journal articles and book chapters from medical and nursing literature, and internet resources. CONCLUSION: A single molecular marker may function in a variety of roles (ie, markers of risk, diagnostics, prognostics, intermediate endpoints). In some instances the molecule can also function as a target of therapeutic intervention. IMPLICATIONS FOR NURSING PRACTICE: Nursing implications include a better understanding of the nature of biomarkers and the multiplicity of their applications, especially with regard to therapeutic targets.

Lung cancer screening: promise and pitfalls.

OBJECTIVES: To provide an overview of the status of lung cancer screening. DATA SOURCES: Published articles, book chapters, websites, and research studies. CONCLUSION: Screening with chest x-ray and sputum cytology has not been shown to be effective in reducing lung cancer mortality. Although screening with helical CT is currently under investigation in randomized clinical trials, observational studies have not shown evidence that it can detect lung cancer that is curable. IMPLICATIONS FOR NURSING PRACTICE: As health care educators and caregivers, nurses should be informed of the status and current controversies associated with lung cancer screening.

Chemoprevention: a primary cancer prevention strategy.

OBJECTIVES: To review cancer chemoprevention clinical trials, and to discuss associated roles, responsibilities, and challenges for nursing. DATA SOURCES: Journal articles, textbooks, and government reports. CONCLUSION: Chemoprevention offers a promising approach to primary cancer prevention for a variety of organ systems. Candidate agents are rigorously evaluated for safety and efficacy through the chemoprevention clinical trials process. IMPLICATIONS FOR NURSING PRACTICE: Chemoprevention is an emerging discipline in which complex clinical trials are being conducted. Nurses play key roles in planning, coordinating, and implementing these studies.

Pentoxifylline in the treatment of radiation-induced fibrosis.

PURPOSE: Fibrotic sequelae remain the most important dose-limiting toxicity of radiation therapy to soft tissue. Functionally, this is reflected in loss of range of motion and muscle strength and the development of limb edema and pain. Tumor necrosis factor alpha and fibroblast growth factor 2 (FGF2), which are abnormally elevated in irradiated tissues, may mediate radiation fibrovascular injury. PATIENTS AND METHODS: In an open label drug trial, we studied the effects of pentoxifylline (400 mg orally tid for 8 weeks) on 30 patients who displayed late, radiation-induced fibrosis at 1 to 29 years posttreatment (40 to 84 Gy). The primary outcome measurement was change in physical impairments thought to be secondary to radiation, including active and passive range of motion (AROM and PROM), muscle strength, limb edema, and pain. Plasma levels of cytokines (tumor necrosis factor alpha and FGF2) also were measured. Twenty-seven patients completed baseline and 8-week assessments, and 24 patients completed baseline, 8-week, and 16-week assessments. RESULTS: After 8 weeks of pentoxifylline intervention, 20 of 23 patients with impaired AROM and 19 of 22 with impaired PROM improved; 11 of 19 patients with muscle weakness showed improved motor strength; five of seven patients with edema had decreased limb girth; and nine of 20 patients had decreased pain. Pretreatment FGF2 levels dropped from an average of 44.9 pg/mL to 24.0 pg/mL after 8 weeks of treatment. CONCLUSION: Patients receiving pentoxifylline demonstrated improved AROM, PROM, and muscle strength and decreased limb edema and pain. Reversal of these delayed radiation effects was associated with a decrease in circulating FGF2.