Use of a web-based app to improve postoperative outcomes for patients receiving gynecological oncology care: A randomized controlled feasibility trial.

OBJECTIVE: Nearly 1 in 5 patients hospitalized for ovarian cancer surgery are readmitted for complications that may have been prevented with monitoring. We conducted a randomized controlled feasibility trial to evaluate a postoperative web-based app intervention to provide real-time symptom monitoring among patients diagnosed or with suspected gynecological cancer who had open bilateral salpingo-oophorectomy surgery. METHODS: Participants were randomized into two groups: (1) App + Reminder: had access to the app, and use was encouraged with daily and/or weekly reminders; (2) app: had access to the app but received no reminders. The app displayed discharge instructions and queried symptoms. Patients' self-reported health information was integrated into their electronic health records. Outcomes above a predetermined threshold triggered alerts that indicated a patient may need medical intervention. Participants completed a questionnaire at baseline and 30-day follow-up. They were also invited to provide qualitative, post-intervention feedback. RESULTS: We screened 35 patients, with high rates of recruitment (74%, N = 26) and completion (93%, N = 24). Participants in the App + Reminder group had more frequent app use relative to the app group (p = 0.05). Using differences-in-differences (DID) analysis for quality of life, the App + Reminder group had relative increase in the mental health score (DID = 7.51, p = 0.15) but decrease in the physical health score (DID = -7.49, p = 0.13). Participant feedback suggested the relative decrease in physical quality of life was attributable to the app activating patients' focus on physical symptoms, not the intervention. CONCLUSION: The pilot established feasibility, acceptability, and some potential benefits of a new web-based app intervention for gynecological oncology postoperative care.

Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma.

BACKGROUND: This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma. METHODS: Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression-free rate (PFR) at 12 weeks (PFR12). RESULTS: Forty-one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%-81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%-55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression-free survival was 4.4 months (95% CI, 3.2-6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5-16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy. CONCLUSIONS: The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017;123:4640-4647. © 2017 American Cancer Society.

Analysis of the psychological impact of cancer-related symptoms on patients with non-small cell lung cancer.

BACKGROUND: Patients with non-small cell lung cancer (NSCLC) experience adverse physical symptoms because of cancer, cancer treatment, and comorbidities. The relations among Cancer-Related Symptoms, Functional Impairment, and Psychological Symptoms in patients with NSCLC is not well understood. METHODS: Retrospective analysis of patient-reported symptoms with the 38-item Patient Care Monitor survey, collected in routine clinical care for 1138 patients with NSCLC at eight US community oncology practices. Study sample was randomly split, and structural equation models examined the direct and mediated effects of Cancer-Related Symptoms and Functional Impairment on symptoms of acute distress (Distress) and depression (Despair) in the training sample. The training model was cross validated in testing sample. Results are presented for the full model using the entire sample. RESULTS: Patients were 48.3% female, with mean age of 66.0 years. The most common comorbidities were anemia (60.8%) and respiratory disease (24.5%). Severity of Cancer-Related Symptoms was strongly and positively related to Functional Impairment and Psychological Symptoms in both training and testing models. The modeled effect of Functional Impairment on Distress and Despair was significant in the overall model using the total sample, and significant or near-significant in the training and testing models. The mediated effect of Cancer-Related Symptoms by Functional Impairment tended to be weaker than its direct modeled effect on Distress and Despair. CONCLUSIONS: Despite prior research suggesting that Functional Impairment plays a larger role than symptom burden in depression in NSCLC, the independent modeled effects of Functional Impairment were no greater than the direct modeled effects of Cancer-Related Symptoms. Copyright © 2016 John Wiley & Sons, Ltd.

Phase II clinical trial of bevacizumab with albumin-bound paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma.

OBJECTIVE: We examined the safety and efficacy of combining bevacizumab with albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma. METHODS: Patients had measurable disease per RECIST guidelines, progressing within 6 months after a prior course of platinum-based treatment. Patients received ab-paclitaxel 100mg/m(2) given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28-day cycle with bevacizumab 10mg/kg given on days 1 and 15. RESULTS: Forty-eight patients with an average 1.8 prior lines of treatment participated. The overall response rate was 50% (24/48) (95% CI, 34.8% - 65.1%), with 4 complete and 20 partial responses. Fourteen patients (29%) had stable disease, whereas eight (17%) had progressive disease, and two (4%) were not evaluable. Patients received a median of 6 treatment cycles (range, 1 - 31 cycles). The median progression-free survival was 8.08 months (95% CI, 5.78 - 10.15 months); 6 month progression-free rate was 62.5% (95% CI, 47.8%-77.2%); median overall survival was 17.15 months (95% CI, 13.57 - 23.82 months). Grade 3-4 adverse events included gastrointestinal disorders (18.8%), neutropenia (8.3%), and hypertension (6.3%). CONCLUSIONS: Ab-paclitaxel with bevacizumab clearly demonstrates antitumor activity and manageable toxicity profile in patients with recurrent, platinum-resistant ovarian carcinoma. This regimen should be evaluated in a larger randomized trial.

Hematologic outcomes and blood utilization in cancer patients with chemotherapy-induced anemia (CIA) pre- and post-national coverage determination (NCD): results from a multicenter chart review.

PURPOSE: In July 2007, the Centers for Medicare and Medicaid Services (CMS) limited coverage of erythropoiesis-stimulating agents (ESAs) in cancer patients with chemotherapy-induced anemia (CIA) through a National Coverage Determination (NCD). The primary objective of this study was to compare transfusion rates in patients with CIA with lung, breast, or colorectal cancer before and after the NCD. METHODS: Adult Medicare patients with CIA treated at 49 community oncology clinics were selected from two time periods based on clinics' NCD implementation date. Chart data were abstracted for 12 weeks post-CIA episode start, defined as hemoglobin (Hb) level <11 g/dL while receiving chemotherapy or within 60 days of the last chemotherapy dose. Multivariate analyses were used to calculate the odds of transfusion and to assess the units of blood transfused, controlling for differences in demographics, clinical history, and chemotherapy. RESULTS: Eight hundred pre-NCD and 994 post-NCD patients from 49 sites were selected. Of the patients, 56% used ESAs post-NCD vs. 88% pre-NCD (p < 0.0001). The duration of ESA use decreased in the post-NCD (32.1 days) vs. pre-NCD (48.4 days, p < 0.0001) group. The post-NCD group reported significantly lower Hb levels, higher odds of receiving a transfusion (odds ratio: 1.41, 95% CI 1.05-1.89, p = 0.0238) and increased blood utilization of 53% (units transfused: OR 1.53, 95% CI 1.15-2.04, p = 0.0034). CONCLUSIONS: Decreased frequency and duration of ESA administration were reported in the post-NCD vs. pre-NCD period. Findings were accompanied by a modest but statistically significant increase in transfusions and a decrease in Hb values.

Retrospective study of the effect of disease progression on patient reported outcomes in HER-2 negative metastatic breast cancer patients.

BACKGROUND: This retrospective study evaluated the impact of disease progression and of specific sites of metastasis on patient reported outcomes (PROs) that assess symptom burden and health related quality of life (HRQoL) in women with metastatic breast cancer (mBC). METHODS: HER-2 negative mBC patients (n = 102) were enrolled from 7 U.S. community oncology practices. Demographic, disease and treatment characteristics were abstracted from electronic medical records and linked to archived Patient Care Monitor (PCM) assessments. The PCM is a self-report measure of symptom burden and HRQoL administered as part of routine care in participating practices. Linear mixed models were used to examine change in PCM scores over time. RESULTS: Mean age was 57 years, with 72% of patients Caucasian, and 25% African American. Median time from mBC diagnosis to first disease progression was 8.8 months. Metastasis to bone (60%), lung (28%) and liver (26%) predominated at initial metastatic diagnosis. Results showed that PCM items assessing fatigue, physical pain and trouble sleeping were sensitive to either general effects of disease progression or to effects associated with specific sites of metastasis. Progression of disease was also associated with modest but significant worsening of General Physical Symptoms, Treatment Side Effects, Acute Distress and Impaired Performance index scores. In addition, there were marked detrimental effects of liver metastasis on Treatment Side Effects, and of brain metastasis on Acute Distress. CONCLUSIONS: Disease progression has a detrimental impact on cancer-related symptoms. Delaying disease progression may have a positive impact on patients' HRQoL.

A retrospective study of quality of life in a community sample of patients with early stage breast cancer.

Few studies have examined the pattern of change in quality of life (QoL) over time among patients with breast cancer, or the impact of disease recurrence on QoL. This retrospective study examined QoL among patients with stage I-IIIB breast cancer. Individual, disease and treatment characteristics were abstracted from the medical record, and linked with QoL data collected as a routine part of patient care. The sample included patients with nonrecurrent (N = 100) and recurrent (N = 19) disease, who completed 1,449 QoL assessments. Linear mixed model analysis showed that disease recurrence significantly and adversely affected QoL across all domains. QoL did not appear to deteriorate before recurrence. The pattern of adjustment after recurrence varied across QoL domains in theoretically consistent ways. Study findings suggest that patients show improvement in some areas after recurrence, but generally do not recover previous levels of QoL.

Patient and practice impact of capecitabine compared to taxanes in first-/second-line chemotherapy for metastatic breast cancer.

BACKGROUND: Oral chemotherapy regimens have emerged as comparably effective to intravenous regimens with the potential for less resource utilization, fewer treatment side effects and a better quality-of-life outcome. The objective of this retrospective chart review was to examine these issues among patients who received single-agent taxane therapy vs. single-agent capecitabine for first- or second-line treatment of metastatic breast cancer (MBC) METHODS: Data from the medical charts of 61 patients who received single-agent capecitabine, docetaxel, or paclitaxel therapy were supplemented with data from the 38-item Patient Care Monitor (PCM) survey of symptom burden and quality of life, prospectively collected during chemotherapy. The endpoints were PCM index scores, hospitalization during treatment, and the number of clinic visits during treatment. RESULTS: The sample was 75% Caucasian, 16% African-American, with a mean age of 59.4 years. Taxane-treated patients had more clinic visits than capecitabine patients, were more likely to have been hospitalized during treatment, and had worse treatment side effects. Controlling for depression, infusion-treated patients reported greater acute distress at the start of therapy than those on oral medication. CONCLUSION: Capecitabine for MBC was associated with a more favorable outcome regarding treatment side effects and quality of life, with reduced resource burden to patients and providers. Physicians may have differentially selected patients with greater depressive symptoms for capecitabine therapy.

Adherence, reports of benefits, and depression among patients treated with continuous positive airway pressure.

OBJECTIVES: To examine if reported obstructive sleep apnea (OSA) symptom improvement, baseline depressive symptoms, or polysomnographically measured sleep parameters are associated with adherence to continuous positive airway pressure (CPAP). CPAP is a highly effective treatment for OSA. Low adherence to CPAP therapy is common and poorly understood. Depression and lack of perceived benefits from CPAP are possible reasons for low adherence. METHODS: Seventy-eight patients evaluated for OSA at a sleep medicine center agreed to participate in the study; 54 patients completed all study assessments. The Beck Depression Inventory (BDI) and the functional outcomes of sleep questionnaire (FOSQ) were administered before polysomnographic evaluation. A card embedded in the CPAP device electronically recorded adherence. The BDI and FOSQ were administered 1 to 2 months after the baseline measurements were obtained. RESULTS: Baseline depressive symptoms were not correlated with mean duration of CPAP use per night. Reported improvements in OSA symptoms were correlated positively with CPAP adherence. There were significant positive correlations between improvement in depressive symptoms and OSA symptoms after initiation of CPAP therapy. The polysomnographic variables measured did not predict improvement in daytime OSA symptoms or CPAP adherence. Post hoc analyses suggested that those individuals with baseline Apnea Hypopnea Index (AHI) between 40 and 80 experienced more symptom improvement than those with AHI <40 or >80. CONCLUSIONS: Patients with the greatest level of CPAP adherence also reported the greatest improvement in OSA symptoms. Patients who continued to experience OSA symptoms after CPAP treatment also tended to have more depressive symptoms after CPAP treatment.

mHealth: Mobile Technologies to Virtually Bring the Patient Into an Oncology Practice.

Accompanied by the change in the traditional medical landscape, advances in wireless technology have led to the development of telehealth or mobile health (mHealth), which offers an unparalleled opportunity for health care providers to continually deliver high-quality care. This revolutionary shift makes the patient the consumer of health care and empowers patients to be the driving force of management of their own health through mobile devices and wearable technology. This article presents an overview of technology as it pertains to clinical practice considerations. Telemedicine is changing the way clinical care is delivered without regard for proximity to the patient, whereas nonclinical telehealth applications affect distance education for consumers or clinicians, meetings, research, continuing medical education, and health care management. Technology has the potential to reduce administrative burdens and improve both efficiency and quality of care delivery in the clinic. Finally, the potential for telehealth approaches as cost-effective ways to improve adherence to treatment is explored. As telehealth advances, health care providers must understand the fundamental framework for applying telehealth strategies to incorporate into successful clinical practice.

Circadian phase in delayed sleep phase syndrome: predictors and temporal stability across multiple assessments.

STUDY OBJECTIVES: To assess temporal stability across multiple assessments and predictors of circadian phase in participants with delayed sleep phase syndrome (DSPS), relative to normal-sleeping matched controls. DESIGN: Circadian phase was assessed by salivary dim light melatonin onset (DLMO) during 3 laboratory visits, separated by at least 5 days--2 scheduled at the end of the week (Friday) and 1 scheduled at the end of the weekend (Sunday). PATIENTS: Eight young volunteers who met International Classification of Sleep Disorders-Revised criteria for DSPS, and 8 age- and sex-matched controls (age range 19-27 years old). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: As expected, salivary DLMO occurred significantly later in patients with DSPS than in controls (F 10.561, p = .006). However, circadian phase did not change significantly across the 3 DLMO assessments in either group. Estimations of circadian phase were not significantly different in the assessments conducted on weekdays versus weekends. Predictors of circadian phase included time of morning light exposure (R2 = 0.777; p < .001), recent wake time (R2 = 0.701, p < .001), and self-reported chronotype (R2 = 0.320, p = .016). DLMO preceded wake time in both groups by approximately 10.75 hours. CONCLUSIONS: Across serial laboratory assessments on an ad lib sleep schedule, patients with DSPS appeared more similar to than different from normal-sleeping control subjects, except for a stable delay in circadian phase.

Emerging research on the treatment and etiology of secondary or comorbid insomnia.

Secondary insomnia is defined as difficulty initiating or maintaining sleep that occurs as a consequence of another primary medical or psychiatric disorder. This distinction from primary insomnia has been thought to be important from a diagnostic standpoint so that treatment for secondary insomnia can appropriately target the primary disorder. By convention, treating insomnia directly has only been recommended with primary insomnia. However, a number of recent studies of cognitive-behavioral treatment for a wide range of secondary insomnias have demonstrated that this approach is an effective treatment in this population. These results are not predicted by the traditional conceptualization of secondary insomnia. Results of epidemiological research also argue against viewing insomnia that is comorbid with another disorder as being caused by that disorder. A revised model is needed to understand insomnia that is comorbid with medical and/or psychiatric illness, in addition to re-evaluating standard treatment protocols for comorbid insomnia.

Recent developments in the classification, evaluation, and treatment of insomnia.

Sleep/wake complaints, and specifically insomnia, are some of the more common problems encountered in the outpatient setting. Despite its prevalence, few clinicians are experts at diagnosing and treating this entity. Additionally, diagnosis and treatment of insomnia is a time-intensive process (often the initial interview takes at least 1 h, depending on the complexity of the insomnia). With a conservative estimate of the annual cost of insomnia between dollar 92.5 and dollar 107.5 billion dollars, it is becoming clear that insomnia has significant medical and public health implications. A problem that has hampered insomnia research is the lack of a standard definition of insomnia for use in research, as well as guidelines for assessment. In recent years, there have been important advances in the classification, evaluation, and treatment of insomnia with efforts to establish greater consensus in how to define and measure insomnia. Cognitive behavioral and pharmacologic therapies have been shown to be effective treatment approaches. Insomnia is a complex entity, often multifactorial in its etiology; and as research and clinical guidelines are established and validated (leading to better data interpretation), continued enhancement of our understanding of this disorder is expected.

The effect of sleep fragmentation on daytime function.

It is clear from this literature that fragmented sleep is less restorative than consolidated sleep, and leads to sleepiness-related daytime impairment. The optimal approach to the quantification of sleep fragmentation continues to be debated. Modest and erratic correlations between measures of sleepiness and traditional measures of EEG arousals have pushed investigators to try and find more sensitive measures of sleep fragmentation. Simply correlating various measures of sleep fragmentation with a measure of sleepiness has significant limitations. Since sleep fragmentation is not the only factor affecting daytime sleepiness, these correlations can be misleading. For example, a subject with severely fragmented sleep will show elevated sleepiness during the day. However, the overall correlation may be reduced because lack of fragmented sleep does not guarantee that the level of sleepiness will be low. Multivariate statistical modeling is needed to account for sources of variance simultaneously in the prediction of daytime sleepiness. In this way it may be possible to identify the optimal definition of sleep fragmentation. More studies are needed that evaluate "sub-cortical" arousals, EEG arousals, and daytime function simultaneously. Ideally, clarification of these measurement issues will lead to an improved understanding of sleep structure and the mechanism through which sleep fragmentation impacts daytime function.

Daytime sleepiness and alertness in patients with Parkinson disease.

STUDY OBJECTIVES: The goal of the study was to objectively measure daytime sleepiness and alertness in patients undergoing treatment for idiopathic Parkinson disease (PD) and assess potential contributing factors. DESIGN: Prospective study. SETTING: An accredited sleep disorders center in a university-based medical center in a large urban area. PATIENTS: Twenty consecutive subjects with idiopathic PD were recruited from a tertiary-care movement disorders clinic. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Patients underwent polysomnography, with a Multiple Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test (MWT) on the following day. Forty-seven percent of the sample was pathologically sleepy according to the MSLT, but only 26% had abnormal MWT scores. There was also a different pattern of correlations between predictors of sleepiness and MSLT and MWT scores. Percentage of stage 1 sleep had the largest correlation with MSLT (-0.42), while pergolide equivalents had the largest correlation with MWT (-0.70). CONCLUSIONS: In this sample of subjects with PD, severe daytime sleepiness was common and was related to poor sleep quality. Daytime alertness as measured by the MWT was impaired as medication burden increased.

Derivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work Group.

Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.

Use of sleep hygiene in the treatment of insomnia.

Sleep hygiene (SH) refers to a list of behaviors, environmental conditions, and other sleep-related factors that can be adjusted as a stand-alone treatment or component of multimodal treatment for patients with insomnia. This paper presents a review of SH, how this concept has been applied and often modified over the past 24 years, and how it relates to the modern sleep disorder nosology, particularly Inadequate Sleep Hygiene. Although a recognized and commonly utilized treatment option, there is no absolute consensus about which steps must be included to constitute SH treatment, and there is much overlap between SH and other cognitive-behavioral treatments for insomnia such as Stimulus Control Procedures and Sleep Restriction Therapy. The literature on the effects of manipulations of individual components of SH under experimental conditions (e.g. effects of presleep alcohol or caffeine intake) in normal sleepers show mixed results. Empirical data demonstrating the role of poor SH as a contributor to insomnia, or showing that good SH improves sleep in patients with insomnia, is not available. Instead of evaluating the impact of a comprehensive list of SH recommendations, a focus on guidelines for use of individual rules is needed.

Sleep and quality of life in breast cancer patients.

This study described sleep in a heterogeneous sample of breast cancer patients using the Pittsburgh Sleep Quality Index (PSQI) and examined the relation between sleep disturbance and health-related quality of life as measured by the Rand 36-Item Health Survey. Chemotherapy and radiation therapy were explored as predictors of sleep disturbance in breast cancer patients, and the sleep characteristics of breast cancer patients were compared to the sleep characteristics of a sample of medical patients with general medical conditions. Results showed that 61% of breast cancer patients had significant sleep problems. Sleep was characterized by reduced total sleep time with sleep frequently being disturbed by pain, nocturia, feeling too hot, and coughing or snoring loudly. Despite the frequency of significant sleep disturbance, pharmacological and cognitive-behavioral treatments of sleep problems were observed to be inadequate. Limited evidence was found for the role of chemotherapy and radiation therapy in the sleep disturbance of breast cancer patients, and the general pattern of sleep disturbance in breast cancer patients was not significantly different than that observed in medical patients with general medical conditions. Breast cancer patients having significant sleep problems had greater deficits in many areas of health-related quality of life. The implications of the findings and study limitations are discussed.

Treatment patterns and outcomes among patients with metastatic melanoma treated in community practice.

BACKGROUND: The primary systemic treatments for advanced melanoma have been chemotherapy and immunotherapy. New agents are currently in development. OBJECTIVES: This study aimed to characterize treatment patterns and outcomes across several lines of therapy and to illustrate the treatment landscape prior to the approval of new therapies. The study endpoints were progression-free survival (PFS), overall survival (OS), and best overall response within line of therapy. METHODS: A retrospective chart analysis was conducted at 11 community oncology practices in the USA. Data for patients aged ≥18 years and diagnosed with stage IV and/or metastatic melanoma during 2006-2010 were analyzed. Primary endpoints were PFS within line of therapy and OS from the diagnosis of metastasis. RESULTS: Data on a total of 202 patients were collected. The sample was mostly male (60%) and Caucasian (88%), with a mean age of 61.3 years. Of the 202 patients, 56 (28%) never received any systemic therapy. In the remaining 146 patients, systemic therapies included temozolomide-based regimens (n = 68), platinum-based regimens without temozolomide (n = 16), other regimens (n = 23), and research regimens (n = 39). Of the 146 patients who received systemic therapy, not all did so immediately after the diagnosis of metastasis: 102 (51%) patients did so shortly after diagnosis and before first disease progression, and 44 (22%) did so after first disease progression. Response rates were very low (≤5%) and did not differ across treatment groups. Progressive disease was the most frequent best overall response category identified, with rates of 83, 78, and 89% in the first to third lines of treatment, respectively. In 146 patients receiving first-line systemic therapy, median PFS was 3.25 months. Median OS in the entire sample was 7.66 months. CONCLUSIONS: Findings provided little evidence for any beneficial effects of the treatments available in the timeframe referred to in this study. Few patients (≤5%) responded to treatment, PFS among treated patients was short (3.25 months in first-line treatments, less in later lines), and there was no evidence of a differential effect of treatment regimens on PFS. There was no evidence of shorter survival in patients who never received systemic therapy. The high proportion of patients who did not receive any systemic therapy highlights the lack of effective therapies and underscores the unmet medical need in this patient population.

Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.

BACKGROUND: In this phase II study, we explored efficacy and toxicity of combined endocrine and low-dose metronomic chemotherapy therapy consisting of fulvestrant and capecitabine in estrogen and/or progesterone receptor-positive, HER2-negative MBC. PATIENTS AND METHODS: Patients with ≤ 1 previous hormonal treatment in the metastatic setting received an injection fulvestrant loading dose 500 mg on day 1, 250 mg on days 15 and 29 followed by 250 mg every 28 days along with continuous oral capecitabine in divided doses. The total fixed daily dose of capecitabine was either 1500 mg or 2000 mg, depending on the patient's weight (< 80 kg vs. ≥ 80 kg). Primary end points were PFS and TTP. Toxicity was assessed by continuous evaluations of treatment-emergent adverse events (AEs) and changes from baseline in laboratory values. RESULTS: Forty-one women, with a mean age of 64.5 years, were enrolled. Patients completed a median of 11 monthly treatment cycles. Median PFS was 14.98 months (95% confidence interval [CI], 7.26-upper limit [UL] not estimated) and median TTP was 26.94 months (95% CI, 7.26-UL not estimated). Median overall survival was 28.65 months (95% CI, 23.95-UL not estimated). Treatment was well tolerated with < 10% Grade 3 palmar-plantar erythrodysesthesia. Overall, the most frequent AEs were palmar-plantar erythrodysesthesia, fatigue, and nausea. CONCLUSION: Fulvestrant with metronomic capecitabine demonstrates substantial activity in hormone receptor-positive MBC and is well tolerated. Combined chemoendocrine approaches should be further explored considering the low toxicity of the combination with meaningful TTP.