Use of Adjuvant Cisplatin-Based Versus Carboplatin-Based Chemotherapy in Non-Small-Cell Lung Cancer: Findings From the Florida Initiative for Quality Cancer Care.

PURPOSE: For patients with resected non-small-cell lung cancer, national guidelines recommend cisplatin-based doublet chemotherapy as the preferred treatment. However, many patients receive a carboplatin-based regimen instead. We aimed to identify factors associated with use of a cisplatin-based regimen and explore its association with other quality-of-care measures. METHODS: This analysis was part of the Florida Initiative for Quality Cancer Care, an audit and feedback project among 11 medical oncology practices. Feedback-sharing sessions based on findings of year 2006 took place in 2008. Eligible patients were random samples of those with resected stage I to III non-small-cell lung cancer treated in 2006 and 2009. RESULTS: In both years combined, 81 patients received adjuvant platinum-based doublets: 33 patients (41%) received cisplatin, and 48 patients (59%) received carboplatin. Use of a cisplatin-based doublet significantly increased in 2009 compared with 2006, from 24% to 56% (P = .006). Multivariable analysis determined that academic practices used cisplatin more frequently than nonacademic practices (odds ratios, 3.26; 95% CI, 1.19 to 8.91; P = .02). Moreover, patients treated in 2009 were more likely to receive cisplatin than those treated in 2006 (odds ratio, 4.89; 95% CI, 1.75 to 13.67; P = .002). No significant association between use of cisplatin and other quality-of-care measures was found. CONCLUSION: In this study, academic practice status and treatment year predicted use of adjuvant cisplatin-based chemotherapy. The increase in use of cisplatin in 2009, as compared with 2006, suggests that audit and feedback may be effective ways to promote such use.

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention.

Preclinical, epidemiologic, and prior clinical trial data suggest that green tea catechins (GTC) may reduce prostate cancer risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E (PolyE), a proprietary mixture of GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms. No differences in the number of prostate cancer cases were observed: 5 of 49 (PolyE) versus 9 of 48 (placebo), P = 0.25. A secondary endpoint comparing the cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3 of 26 (PolyE) versus 10 of 25 (placebo), P < 0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared with the placebo arm (5/25). A decrease in serum prostate-specific antigen (PSA) was observed on the PolyE arm [-0.87 ng/mL; 95% confidence intervals (CI), -1.66 to -0.09]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP.

Florida Initiative for Quality Cancer Care: Changes in Psychosocial Quality of Care Indicators Over a 3-Year Interval.

PURPOSE: Identifying and addressing psychosocial concerns is increasingly recognized as an important aspect of cancer care that needs to be improved. As part of the Florida Initiative for Quality Cancer Care, medical record reviews were conducted to evaluate cancer care, including psychosocial care, at oncology practices in Florida in 2006. Results were subsequently disseminated to the practices, and performance was reassessed at the same practices in 2009. METHODS: Data were available for patients with colorectal, breast, and non-small-cell lung cancer first seen by a medical oncologist in 2006 (n = 1,609) and 2009 (n = 1,720) at the same 10 practice sites. Performance on each psychosocial indicator was evaluated for overall change over time and for variability in change based on practice site and cancer type. RESULTS: The percentage of patients identified as having a problem in emotional well-being increased significantly over time, from 24% to 31% among those assessed (P = .002) and from 13% to 16% overall (P = .026). In contrast, there no significant changes over time in assessment of emotional well-being (53% to 51%, P = .661) or in action taken to address problems (57% to 45%, P = .098). CONCLUSION: Findings suggest more intensive efforts than audit and feedback will be required to improve the quality of psychosocial care and that greater recognition of problems with emotional well-being may tax the ability of practices to link patients with appropriate services. Systematic research is needed to identify and disseminate effective strategies for implementing routine assessment of well-being and addressing the increased demands for care this will generate.

Florida Initiative for Quality Cancer Care: improvements in breast cancer quality indicators during a 3-year interval.

BACKGROUND: The Florida Initiative for Quality Cancer Care (FIQCC), composed of 11 practice sites across Florida, conducted its initial evaluation of adherence to breast cancer quality of care indicators (QCI) in 2006, with feedback provided to encourage quality improvement efforts at participating sites. In this study, our objective was to reassess changes over time resulting from these efforts. STUDY DESIGN: Quality care indicators were derived from the Quality Oncology Practice Initiative, the National Comprehensive Cancer Network, the American College of Surgeons, and expert panel consensus. Medical records were reviewed for breast cancer patients first seen by medical oncologists in 2009 at the FIQCC sites, using the same performance indicators as in 2006. Statistical comparisons of 2006 vs 2009 data across sites were made by Pearson chi-square exact test using Monte Carlo estimation. RESULTS: Charts of 602 patients in 2006 and 636 patients in 2009 were compared. Performance on medical oncology QCI improved over time for documentation of clinical trial participation discussion (p = 0.001), documentation of consent for chemotherapy (p = 0.047), definitive surgery done after neoadjuvant chemotherapy (p = 0.017), and planned dose of chemotherapy consistent with published regimens (p = 0.02). Improvements in surgical QCI were seen for documentation of specimen orientation (p < 0.001), inking of margins (p < 0.0001), and performance of sentinel lymph node biopsy (p = 0.035). CONCLUSIONS: The 2006 FIQCC study identified several medical and surgical oncology QCI improvement needs. Quality improvement efforts resulted in better performance for numerous metrics, therefore speaking to the benefits of reassessment of adherence to performance indicators to guide QCI efforts.

Changes in the care of non-small-cell lung cancer after audit and feedback: the Florida initiative for quality cancer care.

PURPOSE: Audit and feedback have been widely used to enhance the performance of various medical practices. Non-small-cell lung cancer (NSCLC) is one of the most common diseases encountered in medical oncology practice. We investigated the use of audit and feedback to improve the care of NSCLC. METHODS: Medical records were reviewed for patients with NSCLC first seen by a medical oncologist in 2006 (n = 518) and 2009 (n = 573) at 10 oncology practices participating in the Florida Initiative for Quality Cancer Care. In 2008, feedback from 2006 audit results was provided to practices, which then independently undertook steps to improve their performance. Sixteen quality-of-care indicators (QCIs) were evaluated on both time points and were examined for changes in adherence over time. RESULTS: A statistically significant increase in adherence was observed for five of 16 QCIs. Adherence to brain staging using magnetic resonance imaging or computed tomography scan for stage III NSCLC (57.8% in 2006 v 82.8% in 2009; P = .001), availability of chemotherapy flow sheet (89.2% v 97.0%; P < .001), documentation of performance status for stage III and IV disease (43.4% v 51.3%; P < .001), availability of pathology report for patients undergoing surgery (95.2% v 99.2%; P = .02), and availability of signed chemotherapy consent (69.5% v 76.3%; P = .04). There were no statistically significant decreases in adherence on any QCIs. CONCLUSION: Audit with feedback was associated with a modest but important improvement in the treatment of NSCLC. Whether these changes are durable will require long-term follow-up.

Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer.

PURPOSE: We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients were randomly assigned 2:1 to the trial's experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if both were high. In the control arm, patients received gemcitabine/carboplatin. The trial was powered for a 32% improvement in 6-month progression-free survival (PFS). RESULTS: Of 331 patients registered, 275 were eligible. The median number of cycles given was four in both arms. A tumor rebiopsy specifically for expression analysis was required in 17% of patients. The median time from informed consent to expression analysis was 11 days. We found no statistically significant differences between the experimental arm and the control arm in PFS (6.1 months v 6.9 months) or overall survival (11.0 months v 11.3 months). A subset analysis revealed that patients with low levels for both proteins who received the same treatment in both treatment arms had a statistically better PFS (P = .02) in the control arm (8.1 months) compared with the experimental arm (5.0 months). CONCLUSION: This demonstrates that protein expression analysis for therapeutic decision making is feasible in newly diagnosed patients with advanced-stage NSCLC. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% (47 of 53) of patients.

Effects of a brief multimedia psychoeducational intervention on the attitudes and interest of patients with cancer regarding clinical trial participation: a multicenter randomized controlled trial.

PURPOSE: The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. PATIENTS AND METHODS: A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. RESULTS: Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. CONCLUSION: A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials.

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

OBJECTIVE: The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. METHODS: We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. RESULTS: Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. CONCLUSION: A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures.

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention.

Degree of variability in performance on breast cancer quality indicators: findings from the Florida initiative for quality cancer care.

PURPOSE: The Florida Initiative for Quality Cancer Care (FIQCC) comprises 11 Florida practice sites that participate in comprehensive reviews of quality of care specific to patients with cancer. Here, we examined site adherence to performance indicators to assess quality of care for patients with breast cancer (BC). METHODS: Quality indicators were scripted on the basis of accepted guidelines from the Quality Oncology Practice Initiative, National Comprehensive Cancer Network, American College of Surgeons, and site-specific expert panel consensus. Comprehensive chart reviews, including both medical and surgical oncology quality measures, were conducted for patients with BC first seen in 2006 by a medical oncologist at one of the sites. Statistical comparisons were made by the Pearson χ(2) exact test, using Monte Carlo estimation. RESULTS: Charts of 622 patients were reviewed. Of the 34 indicators, seven for medical oncology and four for surgical oncology fell below the 85% level of adherence. A statistically significant difference (P < .001) in variation of performance across the sites was found for the following medical and surgical oncology indicators: documentation of menopausal status, family history, informed consent, planned chemotherapy regimen and flow sheet, American Joint Committee on Cancer staging, HER2/neu status, reporting of margin orientation and inking of the margins, histological grade, having a sentinel lymph node biopsy for invasive BC, and obtaining a mammogram within 14 months of definitive surgery. CONCLUSION: The FIQCC has identified how multiple aspects of BC care can be improved. Findings are being used at the participating institutions to guide quality improvement efforts.

Evaluating the quality of psychosocial care in outpatient medical oncology settings using performance indicators.

OBJECTIVE: An American Psychosocial Oncology Society workgroup has developed indicators of the quality of psychosocial care that can be measured through review of medical records. The present report describes the first large-scale use of these indicators to evaluate psychosocial care in outpatient medical oncology settings. METHODS: Medical records of 1660 colorectal, breast and non-small cell cancer patients first seen by a medical oncologist in 2006 at 11 practice sites in Florida were reviewed for performance on indicators of the quality of psychosocial care. RESULTS: Assessment of emotional well-being was significantly less likely to be documented than assessment of pain (52 vs 87%, p<0.001). A problem with emotional well-being was documented in 13% of records and evidence of action taken was documented in 58% of these records. Ten of eleven practice sites performed below an 85% threshold on each indicator of psychosocial care. Variability in assessment of emotional-well being was associated (p<0.02) with practice site and patient gender and age while variability in assessment of pain was associated (p<0.001) with practice site and cancer type. CONCLUSIONS: Findings illustrate how use of the psychosocial care indicators permits identification of specific practice sites and processes of care that should be targeted for quality improvement efforts. Additionally, findings demonstrate the extent to which routine assessment of emotional well-being lags behind routine assessment of pain in cancer patients.

Quality of care in non-small-cell lung cancer: findings from 11 oncology practices in Florida.

BACKGROUND: Limited data on the quality of care in non-small-cell lung cancer (NSCLC) are available. This study aims to assess the quality of care in NSCLC among 11 medical oncology practices in Florida and to explore the impact of practice volume on care. METHODS: Clinical guidelines and existing indicators were reviewed, and an expert survey was conducted to identify a set of process-based quality of care indicators (QI). Medical records of new patients with NSCLC seen in 2006 were retrospectively reviewed for the adherence to these QIs. RESULTS: We reviewed the compliance with a set of 11 QIs (four general and seven NSCLC specific) among 531 patients. The patient median age was 68 years; 51% were male, and 49% had advanced NSCLC. The median adherence rates to general QIs and NSCLC-specific QIs were 95% (range 69% to 99%) and 69% (range 29% to 91%), respectively. We identified three main areas of deficiencies: chemotherapy consenting (69%), brain staging for stage III NSCLC (59%), and performance status assessment for advanced stages (42%). Significant variation in the adherence rates across practice sites was observed in five of 11 QIs. CONCLUSION: On the basis of this data set of participating institutions in Florida, several areas in the care of patients with NSCLC were identified as targets for future quality improvement efforts.

A phase II trial of vinflunine as monotherapy or in combination with trastuzumab as first-line treatment of metastatic breast cancer.

We investigated the microtubulin inhibitor vinflunine­with trastuzumab in human epidermal growth factor receptor-2 (HER2)-positive patients­as first-line metastatic breast cancer therapy. HER2-negative patients received vinflunine on day 1; HER2-positive patients received vinflunine/trastuzumab every 21 days. Forty-eight patients in each treatment group were planned; the sponsor terminated the study early. Thirty-two evaluable patients (vinflunine, 11; vinflunine/trastuzumab, 21) were enrolled. In HER2-positive patients, vinflunine/trastuzumab produced an objective response rate (33%), clinical benefit rate (71%), and progression-free survival (6.2 months). Grade-3/4 neutropenia occurred in 14 (44%) patients; gastrointestinal toxicities were common and six patients were hospitalized for treatment-related toxicity. The vinflunine/trastuzumab combination was active and well tolerated, but our results do not suggest advantages over taxane/trastuzumab or vinorelbine/trastuzumab.

Phase II trial of thalidomide and daily oral dexamethasone for treatment of hormone refractory prostate cancer progressing after chemotherapy.

BACKGROUND: Responses to monotherapy corticosteroid or thalidomide have been described in prostate cancer, in chemotherapy naïve subjects. METHODS: A total of 39 men with hormone refractory, metastatic prostate cancer who had progression during or after at least 1 conventional cytotoxic drug were treated on a single-arm Phase II trial with dexamethasone, 0.75 mg twice a day plus thalidomide, 100-400 mg/day. RESULTS: Best-observed responses included >50% prostate-specific antigen (PSA) reduction with no radiologic progression: 10 of 39 (26%; 95% confidence interval 13% to 42%). An additional 14 of 39 had decreased PSA but then with radiologic or other progression by 12 weeks. Median progression-free survival was 84 days. Toxicity appeared treatable; there were 5 nonfatal thromboses. There was 1 subject who had complete PSA and radiologic response; 4 responders tolerated treatment without progression for more than 1 year. CONCLUSIONS: PSA responses were frequent. Mostly, these were not durable, but some lasted more than a year. Further investigation on determinants of response durability for these or related compounds should be considered. The response rate of the present data does not support Phase III testing of this regimen for this population.