Health Care Policy and Disparities in Health.

ABSTRACT: The United States has seen a 33% decline in age-adjusted cancer mortality since 1991. Despite this achievement, the United States has some of the greatest health disparities of any developed nation. US government policies are increasingly directed toward reducing health disparities and promoting health equity. These policies govern the conduct of research, cancer prevention, access, and payment for care. Although implementation of policies has played a significant role in the successes of cancer control, inconsistent implementation of policy has resulted in divergent outcomes; poorly designed or inadequately implemented policies have hindered progress in reducing cancer death rates and, in certain cases, exacerbated existing disparities. Examining policies affecting cancer control in the United States and realizing their unintended consequences are crucial in addressing cancer inequities.

Development and Testing of a Mobile App to Collect Social Determinants of Health Data in Cancer Settings: Interview Study.

BACKGROUND: Social determinants of health (SDOH) such as lack of basic resources, housing, transportation, and social isolation play an important role for patients on the cancer care continuum. Health systems' current technological solutions for identifying and managing patients' SDOH data largely focus on information recorded in the electronic health record by providers, which is often inaccessible to patients to contribute to or modify. OBJECTIVE: We developed and tested a patient-centric SDOH screening tool designed for use on patients' personal mobile phone that preserves patient privacy and confidentiality, collects information about the unmet social needs of patients with cancer, and communicates them to the provider. METHODS: We interviewed 22 patients with cancer, oncologists, and social workers associated with a US-based comprehensive cancer center to better understand how patients' SDOH information is collected and reported. After triangulating data obtained from thematic analysis of interviews, an environmental scan, and a literature search of validated tools to collect SDOH data, we developed an SDOH screening tool mobile app and conducted a pilot study of 16 dyadic pairs of patients and cancer care team members at the same cancer center. We collected patient SDOH data using 36 survey items covering 7 SDOH domains and used validated scales and follow-up interviews to assess the app's usability and acceptability among patients and cancer care team members. RESULTS: Formative interviews with patients and care team members revealed that transportation, financial challenges, food insecurity, and low health literacy were common SDOH challenges and that a mobile app that collected those data, shared those data with care team members, and offered supportive resources could be useful and valuable. In the pilot study, 25% (4/16) of app-using patients reported having at least one of the abovementioned social needs; the most common social need was social isolation (7/16, 44%). Patients rated the mobile app as easy to use, accurately capturing their SDOH, and preserving their privacy but suggested that the app could be more helpful by connecting patients to actual resources. Providers reported high acceptability and usability of the app. CONCLUSIONS: Use of a brief, patient-centric, mobile app-based SDOH screening tool can effectively capture SDOH of patients with cancer for care team members in a way that preserves patient privacy and that is acceptable and usable for patients and care team members. However, only collecting SDOH information is not sufficient; usefulness can be increased by connecting patients directly to resources to address their unmet social needs.

Tobacco Use and Tobacco Dependence Management.

Tobacco use is a major public health problem and the leading cause of preventable deaths in the United States and worldwide. Tobacco dependence determines tobacco use and is largely due to nicotine addiction. Such dependence is a disease resulting in a strong desire or compulsion to take tobacco, with difficulty in cessation of tobacco, along with persistent use despite overtly harmful consequences.

Clinical trial participation predicts improved survival in older adults receiving allogeneic blood and marrow transplant.

BACKGROUND: Older adults represent a large oncologic demographic and are under-represented within oncology research despite constituting nearly two-thirds of the oncologic population in the United States. Because many social factors influence research participation, those who enroll in research do not reflect the oncology population at large, introducing bias and creating issue with external validity of studies. The same factors that influence study enrollment may also impact cancer outcomes, meaning that those who enroll in studies may already have an improved chance of cancer survival, further skewing results of these studies. This study evaluates characteristics that influence study enrollment in older adults and explore to what degree these factors may influence survival after allogeneic blood or marrow transplantation. METHODS: This retrospective comparison study evaluates 63 adults aged 60 and above undergoing allogenic transplantation at one institution. Patients who elected and declined enrollment in a non-therapeutic observational study were evaluated. Demographic and clinical characteristics between groups were compared and assessed as predictors of transplant survival, including decision to enroll in the study. RESULTS: Participants who chose to enroll in the parent study were not different with regard to gender, race/ethnicity, age, insurance type, donor age, and neighborhood income/poverty level compared to patients who were invited to participate but declined enrollment. The research participant group had higher proportion assessed as being fully active (23.8% vs. 12.7%, p = 0.034) and lower mean comorbidity scores (1.0 vs 2.47, p = 0.008). Enrollment in an observational study independently predicted transplant survival (HR = 0.316, 95% CI 0.12-0.82, p = 0.017). When controlling for relevant confounders of disease severity, comorbidities, and transplant age, enrolling in the parent study was associated with a lower hazards of death following transplant (HR = 0.302, 95% CI 0.10-0.87, p = 0.027). CONCLUSIONS: Despite being demographically comparable, persons who enrolled in one non-therapeutic transplant study had significantly improved survivorship than those who did not participate in observational research. These findings suggest that there are unidentified factors that influence study involvement that may also impact disease survivorship, over-estimating outcomes from these studies. Results from prospective observational studies should be interpreted with the consideration that study participants have an improved chance of survival at baseline.

Disparities in Breast Cancer Outcomes and How to Resolve Them.

There has been a 40% decline in breast cancer age-adjusted death rate since 1990. Black American women have not experienced as great a decline; indeed, the Black-White disparity in mortality in the United States is greater today than it has ever been. Certain states (areas of residence), however, do not see such dramatic differences in outcome by race. This latter finding suggests much more can be done to reduce disparities and prevent deaths. Interventions to get high-quality care (screening, diagnostics, and treatment) involve understanding the needs and concerns of the patient and addressing those needs and concerns. Patient navigators are 1 way to improve outcomes.

Addressing multilevel barriers to clinical trial participation among Black and White men with prostate cancer through the PACCT study.

BACKGROUND: Cancer clinical trial participation is low and inequitable. Partnering Around Cancer Clinical Trials (PACCT) addressed systemic and interpersonal barriers through an observational study of eligibility and an intervention to improve patient-physician communication and trial invitation rates. METHODS: Physicians at two comprehensive cancer centers and Black and White men with prostate cancer participated. Patients were followed for 2 years to determine whether they became potentially eligible for an available therapeutic trial. Potentially eligible patients were randomized to receive a trials-focused Question Prompt List or usual care. Patient-physician interactions were video-recorded. Outcomes included communication quality and trial invitation rates. Descriptive analyses assessed associations between sociodemographic characteristics and eligibility and effects of the intervention on outcomes. RESULTS: Only 44 (22.1%) of participating patients (n = 199) became potentially eligible for an available clinical trial. Patients with higher incomes were more often eligible (>$80,000 vs. <$40,000, adjusted OR = 6.06 [SD, 1.97]; $40,000-$79,000 vs. <$40,000, adjusted OR = 4.40 [SD, 1.81]). Among eligible patients randomized to the intervention (n = 19) or usual care (n = 25), Black patients randomized to the intervention reported participating more actively than usual care patients, while White intervention patients reported participating less actively (difference, 0.41 vs. -0.34). Intervention patients received more trial invitations than usual care patients (73.7% vs. 60.0%); this effect was greater for Black (80.0% vs. 30.0%) than White patients (80.0% vs. 66.7%). CONCLUSIONS: Findings suggest the greatest enrollment barrier is eligibility for an available trial, but a communication intervention can improve communication quality and trial invitation rates, especially for eligible Black patients.

Physicians' use of plain language during discussions of prostate cancer clinical trials with patients.

OBJECTIVE: This study described physicians' use of plain language during patient-physician cancer clinical trial discussions. METHODS: Video-recorded clinical interactions and accompanying transcripts were taken from a larger study of communication and clinical trials (PACCT). Interactions (n = 25) were selected if they included invitations to participate in a clinical trial. We used descriptive, qualitative discourse analysis, a method that identifies language patterns at or above the sentence level. We first excerpted discussions of clinical trials, then identified instances of plain language within those discussions. Finally, we inductively coded those instances to describe physicians' plain language practices. RESULTS: The analysis identified four plain language practices. Lexical simplification replaced medical terminology with simpler words. Patient-centered definition named, categorized, and explained complex medical terminology. Metaphor explained medical terminology by comparing it with known concepts. Finally, experience-focused description replaced medical terminology with descriptions of patients' potential physical experiences. CONCLUSION: These plain language practices hold promise as part of effective information exchange in discussions of cancer clinical trials. Testing is needed to identify patient preferences and the extent to which these practices address patient health literacy needs. PRACTICE IMPLICATIONS: Pending further testing, these plain language practices may be integrated into physician clinical trial and other communication training.

Prevalence of Mental Health and Social Connection among Patients Seeking Tobacco Dependence Management: A Pilot Study.

INTRODUCTION: with regards to tobacco dependence management, there are certain barriers to successful smoking cessation for patients, such as untreated anxiety and depression. Complicating the impact of mental health morbidities on tobacco dependence may be the significant portion of patients whose mental health issues and limited social connections are undiagnosed and unaddressed. We hypothesize that patients with no prior mental health diagnoses who are treated for tobacco dependence have high rates of undiagnosed mental health morbidities. METHODS: patients were recruited from a tobacco treatment clinic in 2021. Every patient who came for an inaugural visit without a prior diagnosis of mental health disease was screened for depression, anxiety, social isolation and loneliness. Sociodemographic variables were collected. RESULTS: over a 12-month period, 114 patients were seen at the tobacco treatment clinic. Of these 114 patients, 77 (67.5%) did not have a prior diagnosis of a mental health disease. The mean age was 54.3 ± 11.2 years, 52 (67.5%) were females, and 64 (83.1%) were Black/African American. The mean age of starting smoking was 19.3 ± 5.2 years, and 43 (55.8%) had never attempted to quit smoking in the past. With regards to mental health screening, 32 (41.6%) patients had a score of 9 or greater on the Patient Health Questionnaire (PHQ) 9, 59 (76.6%) had a score of 7 or greater on the Generalized Anxiety Disorder (GAD) 7, 67 (87.0%) were identified with social isolation and 70 (90.1%) for loneliness on screening. CONCLUSION: there was a high prevalence of undiagnosed mental health morbidities and social disconnection in patients who were actively smoking and were struggling to achieve smoking cessation. While a larger scale study is necessary to reaffirm these results, screening for mental health morbidities and social disconnection may be warranted in order to provide effective tobacco dependence management.

"It All Depends": Patient and Decision Partner Experiences in Cancer Clinical Trial Decision-Making.

While the supporting role of families and friends has been widely recognized in cancer care, little data exist on how they influence patients' decisions regarding clinical trial participation, accounting for patients' decisional preferences. The goal of our study was to examine the process of clinical trial decision-making from the perspective of adults with cancer and their decision partners. Semi-structured interviews were conducted with 12 patients and 12 decision partners-family and friends engaged in the medical decision-making. Themes included: (1) having the ability and confidence to make decisions; (2) gaining insight about clinical trials; (3) trusting someone in the process; and (4) realizing readiness and context. Our findings will enhance understanding of how patients make clinical trial decisions based on decisional preferences from the perspectives of patients and decision partners. The findings may also help to increase clinician awareness and inclusion of decision partners in conversations regarding clinical trials.

Development and pilot test of a physician-focused cancer clinical trials communication training intervention.

Objective: We describe the development and pilot test of a physician-focused, web-based training module designed to improve physician communication related to clinical trials in a diverse cancer patient population. Methods: Researchers and stakeholders developed the training module, which included a video explaining patient-centered communication strategies for discussing trials, and re-enactments of actual clinical interactions. For the pilot test, the module was provided to physician participants in the Partnering Around Cancer Clinical Trials (PACCT) trial at two major urban cancer centers. Questionnaires assessed change in beliefs, behavioral attitudes, knowledge and comfort; and perceptions of the module. Results: Nineteen physicians participated in the pilot test. Most were experienced in discussing trials. Assessments of change were mixed regarding beliefs; they showed marginal improvement in attitudes, and significant improvement in knowledge, but no change in comfort. Feedback on the module was favorable. Conclusions: This stakeholder-developed physician communication training module was acceptable and effective, albeit in this small and highly-experienced physician sample. Future research should determine its effectiveness on communication in clinical settings. Innovation: This is the first physician training module to focus on communicating about clinical trials in a diverse patient population. It offers a web-based format and re-enactments of naturally-occurring clinical interactions.Trial Registration Number: NCT02906241.

Randomized trial of two artificial intelligence coaching interventions to increase physical activity in cancer survivors.

Physical activity (PA) has numerous health benefits. Personalized coaching may increase adherence to PA recommendations, but it is challenging to deliver personalized coaching in a scalable manner. The objective of our study was to determine whether novel artificially intelligent (AI) coaching interventions increase PA among overweight or obese, physically inactive cancer survivors compared to a control arm that receives health information. We conducted a single-center, three-arm randomized trial with equal allocation to (1) voice-assisted AI coaching delivered by smart speaker (MyCoach), (2) autonomous AI coaching delivered by text message (SmartText), and (3) control. Data collection was automated via sensors and voice technology, effectively masking outcome ascertainment. The primary outcome was change in mean steps per day from baseline to the end of follow-up at 4 weeks. Of the 42 randomized participants, 91% were female, and 36% were Black; mean age was 62.1 years, and mean BMI was 32.9 kg/m2. The majority were breast cancer survivors (85.7%). At the end of 4 weeks follow-up, steps increased in the MyCoach arm by an average of 3618.2 steps/day; the net gain in this arm was significantly greater [net difference = 3568.9 steps/day (95% CI: 1483-5655), P value <0.001] compared to control arm, and [net difference = 2160.6 steps/day (95% CI: 11-4310), P value 0.049] compared to SmartText. In conclusion, AI-based voice-assisted coaching shows promise as a practical method of delivering scalable, individualized coaching to increase physical activity in sedentary cancer survivors. Additional research is needed to replicate these findings in a broader population of cancer survivors and to investigate the effects of these interventions in the general population.ClinicalTrials.gov Identifier: NCT03212079, July 11, 2017, https://clinicaltrials.gov/ct2/show/NCT03212079 .

Effects of Behavioral Weight Loss and Metformin on IGFs in Cancer Survivors: A Randomized Trial.

CONTEXT: Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence. DESIGN: Randomized, 3-parallel-arm controlled clinical trial. INTERVENTIONS AND OUTCOMES: Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months. RESULTS: Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P < 0.0001), and -2.8% (P < 0.0001) in self-directed, coach-directed, and metformin groups, respectively. Compared with the self-directed group, participants in metformin had significant decreases on IGF-1 (mean difference in change: -5.50 ng/mL, P = 0.02) and IGF1:IGFBP3 molar ratio (mean difference in change: -0.0119, P = 0.011) at 3 months. The significant decrease of IGF-1 remained in participants with obesity at 6 months (mean difference in change: -7.2 ng/mL; 95% CI: -13.3 to -1.1), but not in participants with overweight (P for interaction = 0.045). There were no significant differences in changes between the coach-directed and self-directed groups. There were no differences in outcomes at 12 months. CONCLUSIONS: In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.

Willingness to Discuss Clinical Trials Among Black vs White Men With Prostate Cancer.

IMPORTANCE: Black individuals are underrepresented in cancer clinical trials. OBJECTIVE: To examine whether Black and White men with prostate cancer differ in their willingness to discuss clinical trials with their physicians and, if so, whether patient-level barriers statistically mediate racial differences. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study used baseline data from Partnering Around Cancer Clinical Trials, a randomized clinical trial to increase Black individuals' enrollment in prostate cancer clinical trials. Data were collected from 2016 through 2019 at 2 National Cancer Institute-designated comprehensive cancer centers; participants were Black and White men with intermediate-risk to high-risk prostate cancer. In mediation analysis, path models regressed willingness onto race and each potential mediator, simultaneously including direct paths from race to each mediator. Significant indirect effect sizes served as evidence for mediation. EXPOSURES: Race was the primary exposure. Potential mediators included age, education, household income, perceived economic burden, pain/physical limitation, health literacy, general trust in physicians, and group-based medical suspicion. MAIN OUTCOMES AND MEASURES: The primary outcome was the answer to a single question: "If you were offered a cancer clinical trial, would you be willing to hear more information about it?" RESULTS: A total of 205 participants were included (92 Black men and 113 White men), with a mean (range) age of 65.7 (45-89) years; 32% had a high school education or lower, and 27.5% had a household income of less than $40 000. Most (88.3%) reported being definitely or probably willing to discuss trials, but White participants were more likely to endorse this highest category of willingness than Black participants (82% vs 64%; χ22 = 8.81; P = .01). Compared with White participants, Black participants were younger (F1,182 = 8.67; P < .001), less educated (F1,182 = 22.79; P < .001), with lower income (F1,182 = 79.59; P < .001), greater perceived economic burden (F1,182 = 42.46; P < .001), lower health literacy (F1,184 = 9.84; P = .002), and greater group-based medical suspicion (F1,184 = 21.48; P < .001). Only group-based medical suspicion significantly mediated the association between race and willingness to discuss trials (indirect effect, -0.22; P = .002). CONCLUSIONS AND RELEVANCE: In this study of men with prostate cancer, most participants were willing to discuss trials, but Black men were significantly less willing than White men. Black men were more likely to believe that members of their racial group should be suspicious of the health care system, and this belief was associated with lower willingness to discuss trials. Addressing medical mistrust may improve equity in clinical research.

Problem Solving to Enhance Clinical Trial Participation Utilizing a Framework-Driven Approach.

Health professionals agree that increasing diversity in clinical trial participants is an important way to improve cancer care and address disparities in outcomes. However, trial participation among minority populations has been low historically and continues to be low. Underrepresentation has resulted in majority groups reaping greater benefit from research findings, thus widening cancer health disparities. Addressing these disparities effectively has proven to be challenging. To maximize diversity among participants, it is necessary to understand the steps patients take to enroll in trials; the barriers patients face at each step; and the needs and preferences of the patient population overall and subgroups specified by age, race, ethnicity, or sex, in order to develop interventions to address barriers to participation. To improve clinical trial participation, and most importantly to eliminate disparities, cancer centers should examine reasons patients fail to enroll in trials and develop interventions designed to meet their patients' needs and preferences.

Patient navigation and clinical trial participation: A randomized controlled trial design.

BACKGROUND: To our knowledge, no published studies utilizing a randomized controlled design have examined the efficacy of patient navigation for improving clinical trial enrollment. METHODS: This patient navigation and clinical trial participation study is a randomized controlled trial to assess the effect of a patient navigator on enrollment into therapeutic cancer clinical trials. Participants are randomly assigned to high intensity, patient navigator-delivered patient educational materials (PEM) and needs assessment vs. low intensity patient navigation (patient navigator-delivered patient educational materials [PEM] alone). Discussion: Effective enrollment strategies may include utilization of patient navigators as away to meet individual needs, barriers, and concerns of participants enrolled in clinical trials.

Increasing Physical Activity Amongst Overweight and Obese Cancer Survivors Using an Alexa-Based Intelligent Agent for Patient Coaching: Protocol for the Physical Activity by Technology Help (PATH) Trial.

BACKGROUND: Physical activity has established health benefits, but motivation and adherence remain challenging. OBJECTIVE: We designed and launched a three-arm randomized trial to test artificial intelligence technology solutions to increase daily physical activity in cancer survivors. METHODS: A single-center, three-arm randomized clinical trial with an allocation ration of 1:1:1: (A) control, in which participants are provided written materials about the benefits of physical activity; (B) text intervention, where participants receive daily motivation from a fully automated, data-driven algorithmic text message via mobile phone (Coachtext); and (C) Voice Assist intervention, where participants are provided with an in-home on demand autonomous Intelligent Agent using data driven Interactive Digital Voice Assist on the Amazon Alexa/Echo (MyCoach). RESULTS: The study runs for 5 weeks: a one-week run-in to establish baseline, followed by 4 weeks of intervention. Data for study outcomes is collected automatically through a wearable sensor, and data are transferred in real-time to the study server. The recruitment goal is 42 participants, 14 in each arm. Electronic health records are used to prescreen candidates, with 39 participants recruited to date. DISCUSSION: This study aims to investigate the effects of different types of intelligent technology solutions on promoting physical activity in cancer survivors. This innovative approach can easily be expanded and customized to other interventions. Early lessons from our initial participants are helping us develop additional advanced solutions to improve health outcomes. TRIAL REGISTRATION: Retrospectively registered on July 10, 2017 at ClinicalTrials.gov: NCT03212079; https://clinicaltrials.gov/ct2/show/NCT03212079 (Archived by WebCite at http://www.webcitation.org/6wgvqjTji).

Partnering around cancer clinical trials (PACCT): study protocol for a randomized trial of a patient and physician communication intervention to increase minority accrual to prostate cancer clinical trials.

BACKGROUND: Cancer clinical trials are essential for testing new treatments and represent state-of-the-art cancer treatment, but only a small percentage of patients ever enroll in a trial. Under-enrollment is an even greater problem among minorities, particularly African Americans, representing a racial/ethnic disparity in cancer care. One understudied cause is patient-physician communication, which is often of poor quality during clinical interactions between African-American patients and non-African-American physicians. Partnering Around Cancer Clinical Trials (PACCT) involves a transdisciplinary theoretical model proposing that patient and physician individual attitudes and beliefs and their interpersonal communication during racially discordant clinical interactions influence outcomes related to patients' decisions to participate in a trial. The overall goal of the study is to test a multilevel intervention designed to increase rates at which African-American and White men with prostate cancer make an informed decision to participate in a clinical trial. METHODS/DESIGN: Data collection will occur at two NCI-designated comprehensive cancer centers. Participants include physicians who treat men with prostate cancer and their African-American and White patients who are potentially eligible for a clinical trial. The study uses two distinct research designs to evaluate the effects of two behavioral interventions, one focused on patients and the other on physicians. The primary goal is to increase the number of patients who decide to enroll in a trial; secondary goals include increasing rates of physician trial offers, improving the quality of patient-physician communication during video recorded clinical interactions in which trials may be discussed, improving patients' understanding of trials offered, and increasing the number of patients who actually enroll. Aims are to 1) determine the independent and combined effects of the two interventions on outcomes; 2) compare the effects of the interventions on African-American versus White men; and 3) examine the extent to which patient-physician communication mediates the effect of the interventions on the outcomes. DISCUSSION: PACCT has the potential to identify ways to increase clinical trial rates in a diverse patient population. The research can also improve access to high quality clinical care for African American men bearing the disproportionate burden of disparities in prostate and other cancers. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT02906241 (September 8, 2016).

The impact of insurance on access to cancer clinical trials at a comprehensive cancer center.

PURPOSE: Cancer patients at Johns Hopkins undergo insurance clearance to verify coverage for enrollment to interventional clinical trials. We sought to explore the impact of insurance clearance on disparities in access to cancer clinical trials at this urban comprehensive cancer center. EXPERIMENTAL DESIGN: We evaluated the frequency of insurance-based denial of access to cancer clinical trials over a 5-year period after initiation of a formal insurance clearance process. We used a case-control design to compare demographic and clinical parameters of patients denied or approved for clinical trials participation by their insurance company in a 3-year interval. RESULTS: From July 2003 to July 2008, insurance requests for clinical trial participation were submitted on 4,617 consented cancer patients at Johns Hopkins. A total of 628 patients (13.6%) with health insurance were denied therapeutic trial enrollment owing to lack of insurance coverage for participation. A total of 254 patients denied enrollment from 2005 to 2007 were selected for further analysis. Two-hundred sixty randomly selected patients approved for clinical trial participation served as controls. Patients approved were on average older (59.2 versus 54.9 years) than patients denied (P = 0.0001). Residents of Pennsylvania, which lacks a state law mandating cancer clinical trial coverage for residents, were overrepresented among the denied patients (P = 0.0009). No statistically significant variance in the likelihood of insurance denial was found on the basis of sex, race, stage of disease, or presence of comorbidities. CONCLUSIONS: Denial of access to therapeutic clinical trials, even among insured patients, is a significant barrier to clinical cancer research. This barrier spans racial, ethnic, and gender categories.

Phase I trial of weekly trabectedin (ET-743) and gemcitabine in patients with advanced solid tumors.

PURPOSE: To determine the maximum tolerated dose (MTD) of trabectedin plus gemcitabine administered on a weekly schedule in patients with advanced solid tumors. METHODS: Patients with ECOG performance status 0-1 and adequate organ function were enrolled. On days 1, 8, and 15 of a 28-day cycle, patients received gemcitabine (starting dose, 800 mg/m(2)) followed by trabectedin (starting dose, 0.3 mg/m(2)). Strict liver function test treatment criteria were employed to avoid hepatic toxicity seen in previous trabectedin studies. Plasma samples were collected during cycles 1 and 2 for pharmacokinetic analyses. RESULTS: Fifteen patients received >or=1 dose, with a median of two treatment cycles (range 1-10). The most common drug-related toxicity was hepatic. Dose reductions were required for trabectedin in four (27%) patients and gemcitabine in six (40%) patients. Cycle delays/dose holds were required in 11 (73%) patients and doses above trabectedin 0.4 mg/m(2) and gemcitabine 1,000 mg/m(2), which is the recommended phase II dose, were not feasible. Seven patients maintained stable disease after two cycles. Gemcitabine and trabectedin pharmacokinetics were not altered substantially with concomitant administration. CONCLUSIONS: Given the lack of pharmacokinetic interaction and potential efficacy of trabectedin and gemcitabine combination therapy, further study is warranted with alternate schedules.