Treatment Duration,Healthcare Resource Utilization,and Costs Among Chemotherapy-Naïve Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate: A Retrospective Claims Analysis

Introduction

Enzalutamide and abiraterone acetate (plus prednisone) are new hormonal treatments for metastatic castration-resistant prostate cancer (mCRPC). This study compared treatment duration, healthcare resource utilization (HRU), and treatment costs for chemotherapy-naïve mCRPC patients treated with enzalutamide or abiraterone acetate in the USA.

Methods

Chemotherapy-naïve mCRPC patients initiating treatment with enzalutamide or abiraterone acetate were identified from administrative claims. Continuous enrollment ≥?6 months before and ≥?3 months after the index date (initiation date of enzalutamide or abiraterone acetate) was required. Treatment duration, all-cause and prostate cancer-related HRU, and costs were estimated during the post-index period. Multivariable analyses compared HRU and costs between cohorts, adjusting for baseline characteristics.

Results

Overall, 920 chemotherapy-naïve patients initiated enzalutamide and 2310 initiated abiraterone acetate (median follow-up, 10.7 and 13.5 months, respectively). More enzalutamide-treated patients had corticosteroid-sensitive comorbidities at baseline. Treatment duration was longer with enzalutamide versus abiraterone acetate (median, 10.7 vs. 8.8 months; P?=?0.008). Enzalutamide was associated with fewer all-cause inpatient admissions [adjusted incidence rate ratio (95% confidence interval) 0.87 (0.76, 0.99)], days of hospitalization [0.84 (0.70, 1.02)], and outpatient visits [0.94 (0.90, 0.98)], and fewer prostate cancer-related outpatient visits [0.92 (0.87, 0.96)] compared with abiraterone acetate. Enzalutamide was also associated with lower prostate cancer-related inpatient and emergency department costs [adjusted differences, $122 (P?=?0.024) and $28 (P?=?0.009), respectively].

Conclusion

Chemotherapy-naïve mCRPC patients treated with enzalutamide versus abiraterone acetate had longer treatment duration and incurred lower HRU and prostate cancer-related inpatient and emergency department costs.

Funding

Astellas Pharma Inc.

     

Long-term mortality in patients with chronic obstructive pulmonary disease following extracorporeal membrane oxygenation for cardiac assist after cardiovascular surgery

Purpose

Information on predisposing risk factors influencing long-term survival after extracorporeal membrane oxygenation (ECMO) support remains scarce. In critically ill patients chronic obstructive pulmonary disease (COPD) is an independent risk factor for mortality and morbidity. We assessed the influence of COPD on cardiovascular and all-cause mortality in patients undergoing ECMO therapy.

Methods

We prospectively included 191 patients undergoing veno-arterial ECMO therapy following cardiovascular surgery at a university-affiliated tertiary care center into our registry.

Results

The median follow-up time was 51 months (IQR 34–71 months) corresponding to 4,197 overall months of follow-up. A total of 125 patients (65 %) died; 88 % of deaths were due to cardiovascular causes. Long-term survival was decreased in patients with COPD after 1 year (23 % vs. 44 %) and after 6 years (14 % vs. 35 %) compared to patients without COPD. COPD was independently associated with all-cause mortality with a hazard ratio of 4.22 (95 % CI 1.04–17.11, p = 0.04) and cardiovascular mortality with a hazard ratio of 5.87 (95 % CI 1.41–24.47, p = 0.02).

Conclusions

We identified COPD as a strong and independent predictor of long-term all-cause mortality and cardiovascular mortality in patients undergoing ECMO therapy following cardiovascular surgery. The current study presents valuable information for a comprehensive decision-making process prior to ECMO implantation and helps to identify high-risk patients that may benefit from intensified treatment of co-morbidities and close check-ups after hospital discharge.     

Survival of metastatic colorectal cancer patients treated with chemotherapy in Alberta (1995–2004)

Goals of work

Clinical trials have suggested that advances in chemotherapy significantly improve the survival of patients with metastatic colorectal cancer. Comparable evidence from clinical practice is scarce. This study aims to investigate the survival of patients with metastatic colorectal cancer treated with chemotherapy in Alberta, Canada.

Patients and methods

Trends of relative survival of patients diagnosed in 1994–2003 were assessed using Alberta Cancer Registry (ACR) data. The median overall survival (OS) of patients diagnosed in 2004 was determined by linking Cancer Registry data with Electronic Medical Records (EMR). Cox regression models were fitted to calculate the hazard ratio for patients treated with chemotherapy.

Results

The 2-year relative survival for patients with metastatic colorectal cancer who received chemotherapy increased significantly from 29% to 41% over the 10 years (1994–2003, p?<?0.015). A 69% reduction in the risk of mortality was observed in the 168 patients who received chemotherapy compared to the 87 patients who did not, after adjusting for age, gender, and number of metastases. The median OS of patients who received chemotherapy was 17.5 months. This is comparable to the 18–20 months seen in recently published clinical trials, considering the patients in this study were from the real clinical practice, nearly half of them were older than 70, and many of them might have important co-morbidities.

Conclusions

The survival of patients diagnosed with metastatic colorectal cancer in Alberta has improved in recent years; this is most likely attributable in large part to the use of chemotherapy.     

Cost-Effectiveness of Second-Line Chemotherapy/Biologics among Elderly Metastatic Colon Cancer Patients

Introduction

Advancements in chemotherapy treatment have improved the clinical management of metastatic colon cancer (mCC) patients. An increasing number of elderly mCC patients receive various combinations of regimens in second-line chemotherapy/biologics treatment (Tx2) after first-line treatment (Tx1) to prolong survival and/or palliate symptoms, but these regimens have higher costs. This analysis investigated the survival benefit and incremental cost associated with Tx2 among elderly mCC patients.

Methods

Elderly (aged ≥66 years) SEER-Medicare patients diagnosed with mCC in 2003–2007 were identified and followed until death or the end of 2009. Cox regression and partitioned least squares regression were utilized to obtain the survival benefit and incremental cost associated with Tx2 within a 5-year study period. A time-varying model was used to reduce bias due to sequential ordering of Tx1 and Tx2. The regressions controlled for patient demographic characteristics, clinical variables, and a proxy for poor performance. Bootstrapping was used to generate 95% confidence intervals (CI).

Results

Of the 3,266 elderly mCC patients who received Tx1, 2,744 (84%) died within the observation period; 1,440 (44%) received Tx2. The survival benefit associated with receipt of Tx2 was 0.33 years (95% CI 0.19–0.43), and the associated incremental cost was $40,888 (95% CI 3,044–44,324). The incremental cost-effectiveness ratio (ICER) for Tx2 was $123,903 per life year gained (95% CI 9,600–216,082).

Conclusion

The estimated survival benefit of receiving second-line chemotherapy/biologics was about 4 months, which is consistent with evidence from clinical trials. This improved survival was associated with an ICER that exceeds the traditional threshold.     

Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy—a systematic review

Background

Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 1–3 days and lasting 5–7 days after taxane-based chemotherapy. Despite negatively impacting patient’s quality of life, little is known about the optimal TAPS management. A systematic review of treatment strategies for TAPS across all tumor sites was performed.

Methods

Embase, Ovid MEDLINE(R), and the Cochrane Central Register of Controlled Trials were searched from 1946 to October 2014 for trials reporting the effectiveness of different treatments of TAPS in cancer patients receiving taxane-based chemotherapy. Two individuals independently screened citations and full-text articles for eligibility. Outcome measures included type of treatment and response of myalgias, arthralgias, pain, and quality of life (QoL).

Results

Of 1614 unique citations initially identified, five studies met the pre-specified eligibility criteria. Two were randomized placebo-controlled trials (225 patients), two were randomized open-label trials 76 patients), and one was a retrospective study (10 patients). The agents investigated included gabapentin, amifostine, glutathione, and glutamine. Study sizes ranged from 10 to 185 patients. Given the heterogeneity of study designs, a narrative synthesis of results was performed. Neither glutathione (QoL, p = 0.30, no 95 % CI reported) nor glutamine (mean improvement in average pain was 0.8 in both treatment arms, p = 0.84, no 95 % CI reported) were superior to placebo. Response to amifostine (pain response) and gabapentin (reduction in taxane-induced arthralgias and myalgias) was 36 % (95 % CI, 16–61 %) and 90 % (no 95 % CI data reported), respectively.

Conclusions

Despite its prevalence in patients receiving taxane-based chemotherapies, TAPS remains poorly researched and few studies evaluate its optimal management. If the management of patients is to be improved, more prospective trials are needed.

     

Change in bone mineral density during adjuvant chemotherapy for early-stage breast cancer

Purpose

Adjuvant chemotherapy has been associated with loss of bone mineral density (BMD) either as a direct effect or due to glucocorticoids used as supportive care medication. A prospective cohort study was conducted to evaluate changes in BMD from baseline to right after completion of chemotherapy, i.e., 4 months.

Methods

Dual-imaging X-ray absorptiometry (DXA) was performed at baseline and after completing anthracycline- and taxane-based chemotherapy to measure BMD in the spine, hip, and forearm in early-stage breast cancer patients. High-dose prednisolone was used at three weekly intervals to reduce nausea and vomiting. Patients were advised a daily calcium/vitamin D supplement. Linear regression was used to assess mean percentage change in BMD and 95 % confidence intervals (95 % CI) according to doses of prednisolone, menopausal status, smoking, and BMI.

Results

Eight patients were excluded: seven because of initiation of bisphosphonate treatment due to osteoporosis at baseline, and one had non-interpretable DXA. The final cohort included 97 patients with a mean age of 53 years (range 34–72). Mean cumulative prednisolone dose was 1308 mg (95 % CI 1255; 1362). BMD increased 1.36 % (95 % CI 0.7; 2.0, p?<?0.001) in the spine and 1.27 % (95 % CI 0.9; 1.7, p?<?0.001) in the hip. Forearm BMD did not change. Postmenopausal women had increases in spine BMD of 2.35 % (95 % CI 1.1; 3.6, p?<?0.001) compared to premenopausal women. The spine BMD of current smokers decreased 1.67 % (95 % CI ?3.3; ?0.1, p?=?0.04) compared to never/former smokers.

Conclusions

Adjuvant chemotherapy supplemented with prednisolone was not associated with loss of BMD. Postmenopausal women gained bone mass, whereas current smokers lost bone mass.

     

Long-term follow-up for cardiovascular disease after chemotherapy and/or radiotherapy for breast cancer in an unselected population

Purpose

Whereas earlier research focused on specific patient groups, this study assessed the risk of cardiovascular disease (CVD) in an unselected population curatively treated for breast cancer (BC), compared with an age-matched random sample of controls.

Methods

Risks were determined in BC survivors and controls. CVD was divided into three categories: congestive heart failure, vascular cardiac diseases, and “other” cardiac diseases. Hazard ratios (HRs) and 95 % confidence intervals (95 % CI) adjusted for age, CVD, and CVD risk factors at baseline were determined by Cox regression analyses.

Results

All 561 survivors of BC experienced surgery of whom 229 received (neo)adjuvant radiotherapy, 145 received chemotherapy (with or without radiotherapy), and 187 received no adjuvant therapy. During follow-up (median 9; range 5–57 years), CVD occurred in 176/561 (31 %) survivors and in 398/1,635 (24 %) controls. After radiotherapy, no increased risks of congestive heart failure (HR 0.5; 95 % CI 0.2–1.8), vascular cardiac diseases (HR 1.1; 95 % CI 0.7–1.7), or other cardiac diseases (HR 1.3; 95 % CI 0.8–2.3) were found compared with controls. Similar results were found after chemotherapy for congestive heart failure (HR 1.8; 95 % CI 0.6–5.8), vascular cardiac diseases (HR 1.1; 95 % CI 0.5–2.3), and other cardiac diseases (HR 1.2; 95 % CI 0.3–5.5).

Conclusions

In an unselected population of BC survivors, no significant increased risk of CVD after radiotherapy and/or chemotherapy was found compared with controls. However, the HRs after chemotherapy were in-line with previous studies. Future studies should include more detailed information on treatment and more specific outcome measures.     

The early discontinuation of palliative chemotherapy in older patients with cancer

Purpose

Older patients with cancer may have an increased risk of early discontinuation of active treatment (ED), which results in poor outcome in curative or adjuvant settings. We aimed to determine the association between survival and ED and to identify predictors of ED in palliative setting.

Methods

Ninety-eight patients older than 65 years of age who received a comprehensive geriatric assessment (CGA) before palliative first-line chemotherapy were analyzed. Clinical information and CGA results were retrieved from electronic medical record. CGA included Charlson’s co-morbidity index, activities of daily living (ADL), instrumental ADL (IADL), Mini-Mental Status Examination, short-form of the geriatric depression scale, timed-get-up-and-go test (TGUG), and mini-nutritional assessment (MNA). ED was defined as no active cancer treatment (radiotherapy and/or chemotherapy) beyond palliative first-line chemotherapy. Predictors of ED were identified using clinical parameters and CGA.

Results

Active treatment was discontinued after first-line chemotherapy in 30 patients during median follow-up period of 15.1 months. ED after first-line chemotherapy was associated with shorter overall survival (OS; median OS?=?3.1 vs. 14.7 months in patients with ED compared with patients without ED, p?<?0.001). Eastern Cooperative Oncology Group performance status, living alone, ADL, IADL, MNA, and TGUG were associated with ED (p?=?0.001, p?=?0.048, p?=?0.001, p?<?0.001, p?<?0.001, p?=?0.002, respectively). In multivariable analysis, malnutrition and dependent IADL were the independent predictive factors for ED (odds ratio?=?5.03; 95 % confidence interval?=?1.50–16.87: odds ratio?=?3.06; confidence interval?=?1.03–9.12, respectively).

Conclusions

ED was associated with shorter OS in older patients with cancer. Malnutrition and dependent IADL were identified as independent predictive factors for ED.     

Occurrence and characterization of everolimus adverse events during first and subsequent cycles in the treatment of metastatic breast cancer

Purpose

Endocrine therapy remains the standard therapy for patients with metastatic hormone receptor (HR)-positive breast cancer. The novel combination of everolimus and exemestane has been shown to prolong progression-free survival but with increased adverse events compared to exemestane alone. In this study, we aimed to describe the frequency and timing of everolimus dose reductions and/or interruptions due to adverse events.

Methods

This is a single-center retrospective case series including all patients who received everolimus in combination with exemestane from May 1, 2012, through July 31, 2013. The primary objective was to determine the incidence of first-cycle interruptions or dose reductions with everolimus.

Results

Forty-six patients were included in the analysis. First-cycle dose reductions or interruptions were observed in 21 (45.6 %) patients. The most common adverse events leading to dose reduction or interruption was stomatitis (57.1 %), fatigue (14.3 %), and diarrhea (14.3 %). The median time to dose reduction was 14 days, and the median duration of the interruption was 14 days. The median progression-free survival was 6.2 months, and the median time to treatment failure was 4.4 months.

Conclusions

In this case series, almost half of the patients treated with everolimus and exemestane required a dose reduction or interruption of everolimus during the first cycle of treatment. This early onset of adverse events requires thorough patient education and close clinical monitoring during the first 28 days of therapy.

     

Specific anticancer treatments in the last 3 months of life: a French experience

Purpose

The treatment of patients with advanced cancer is becoming increasingly aggressive near the end of life, whereas poor literature is available. This study analyzes the management of patients with a solid cancer in their last 3 months of life in the Centre Hospitalier Universitaire de Besançon, France.

Methods

This retrospective study includes all adult patients with a solid tumor who died in medical oncology or radiotherapy unit in 2005, 2006, and 2007. Group A had received at least one specific anticancer treatment at the end of life, while group B did not.

Results

Of 167 included patients, 139 (83.2 %) received a specific treatment during the last 3 months of life. The reference unit was medical oncology for 76 % and radiotherapy for 24 % patients; overall survival was 18 and 9 months, and median age of metastatic evolution was 59 and 71 in group A and B, respectively. The number of previous lines of chemotherapy was on average 1.96 and 0.39, respectively. In a univariate analysis, differences appear for reference unit, age of death, and number of previous lines of chemotherapy, with a trend for chemosensitivity of the tumor in this small-sized study. No significant difference was found for sex, life-threatening metastases, or performance status.

Conclusion

These preliminary data suggest that when evaluating the utilization of care at the end of life, one needs to take into account factors such as the age of the patient and the chemosensitivity of the tumor.     

Transient swelling versus lymphoedema in the first year following surgery for breast cancer

Purpose

The aim was to better understand the incidence, time course and risk factors for swelling in the arm on the side of surgery over the first year following surgery for breast cancer.

Method

Women (n?=?160) were assessed 1 month following surgery and then randomised to the exercise or control group. Reassessment occurred 3, 9 and 15 months following surgery. Potential risk factors for swelling included age, body mass index, side of surgery and surgical and medical treatments for their breast cancer, physical measures of shoulder range of motion and strength, inter-limb arm circumference difference and the group to which they were randomised. Swelling was determined using bioimpedance spectroscopy with reference to previously established cut-offs for lymphoedema.

Results

The number of women with swelling at 3, 9 and 15 months was 15, 15 and 13, respectively; however, at 15 months only 5/13 presented with swelling in either of the preceding assessments. The risk of swelling increased at 3, 9 and 15 months for each centimetre increase in the baseline inter-limb difference in sum of arm circumferences by 1.30, 1.17 and 1.14. In addition, risk of swelling at 3 months was 2.6 times greater for women in the control group; at 9 months, 7 times greater for women who had taxane-based chemotherapy; and at 15 months, the risk increased 1.16 times for each day the drain was in situ.

Conclusion

Swelling in the first year is likely to be transient, and factors including exercise and taxane chemotherapy affect the risk of developing swelling.     

Cardiopulmonary resuscitation among mechanically ventilated patients

Purpose

To evaluate the outcomes, including long-term survival, after cardiopulmonary resuscitation (CPR) in mechanically ventilated patients.

Methods

We analyzed Medicare data from 1994 to 2005 to identify beneficiaries who underwent in-hospital CPR. We then identified a subgroup receiving CPR one or more days after mechanical ventilation was initiated [defined by ICD-9 procedure code for intubation (96.04) or mechanical ventilation (96.7x) one or more days prior to procedure code for CPR (99.60 or 99.63)].

Results

We identified 471,962 patients who received in-hospital CPR with an overall survival to hospital discharge of 18.4 % [95 % confidence interval (CI) 18.3–18.5 %]. Of those, 42,163 received CPR one or more days after mechanical ventilation initiation. Survival to hospital discharge after CPR in ventilated patients was 10.1 % (95 % CI 9.8–10.4 %), compared to 19.2 % (95 % CI 19.1–19.3 %) in non-ventilated patients (p < 0.001). Among this group, older age, race other than white, higher burden of chronic illness, and admission from a nursing facility were associated with decreased survival in multivariable analyses. Among all CPR recipients, those who were ventilated had 52 % lower odds of survival (OR 0.48, 95 % CI 0.46–0.49, p < 0.001). Median long-term survival in ventilated patients receiving CPR who survived to hospital discharge was 6.0 months (95 % CI 5.3–6.8 months), compared to 19.0 months (95 % CI 18.6–19.5 months) among the non-ventilated survivors (p < 0.001 by logrank test). Of all patients receiving CPR while ventilated, only 4.1 % were alive at 1 year.

Conclusions

Survival after in-hospital CPR is decreased among ventilated patients compared to those who are not ventilated. This information is important for clinicians, patients, and family members when discussing CPR in critically ill patients.     

Everolimus Plus Exemestane in Postmenopausal Patients with HR+ Breast Cancer: BOLERO-2 Final Progression-Free Survival Analysis

Introduction

Effective treatments for hormone-receptor-positive (HR⁺) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population.

Methods

BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR⁺ advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints.

Results

Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38–0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31–0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, patients with recurrence during or within 12 months of completion of adjuvant therapy, and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials.

Conclusion

The addition of everolimus to exemestane markedly prolonged PFS in patients with HR⁺ advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.     

Chemotherapy-induced peripheral neuropathy after neoadjuvant or adjuvant treatment of breast cancer: a prospective cohort study

Purpose

The purposes of this study were to estimate the incidence of chemotherapy-induced peripheral neuropathy (CIPN) and to identify its main determinants and impact in patient-reported outcomes.

Methods

We performed a prospective cohort study including 296 patients with incident breast cancer submitted to chemotherapy, followed for 1 year. Patients with incident CIPN were reevaluated 6 months after this diagnosis. Relative risks (RR) with 95 % confidence intervals (95 % CI) were computed to quantify the relation between different clinical characteristics and the occurrence of CIPN, using Poisson regression. The variation of patient-reported outcomes between baseline and 1-year follow-up assessments was compared between patients with and without CIPN.

Results

The cumulative incidence of CIPN in the first year after diagnosis was 28.7 % (95 % CI 23.8–34.1), and more than 80 % of the patients were still symptomatic after 6 months. Among the latter, there was a significant decrease in the median total neuropathy score, clinical version (7 versus 4) between the two periods. In multivariable analysis, the risk of CIPN was higher for treatment with docetaxel (cumulative doses ≤300 mg/m², RR?=?6.96, 95 % CI 2.53–19.10; >300 mg/m², RR?=?13.32; 95 % CI 4.11–43.14). Alcohol consumption and diabetes were not significantly associated with CIPN. There were no significant differences in the variation of patient-reported outcomes between the baseline and 1-year follow-up evaluations.

Conclusions

CIPN was frequent in this contemporary cohort of early-stage breast cancer patients and was strongly associated with docetaxel-based regimens. Symptoms persisted for at least 6 months in most patients, but severity was low and CIPN had no impact on patient-reported outcomes.

     

Outcome and late effects among acute myeloid leukemia survivors: a nationwide population-based study

Background

Understanding of pathogenesis and treatment for acute myeloid leukemia (AML) is growing. However, studies regarding the outcomes and late effects among AML survivors are relatively limited.

Methods

This nationwide population-based study used medical records from the Taiwanese National Health Insurance Research Database. A total of 3356 AML patients diagnosed from 2000 to 2008 were analyzed. The physiological and psychological morbidities in AML survivors were compared to those identified from a normal population. This study also compared late effects among AML survivors treated by intensive chemotherapy alone and allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Results

The incidence of AML in Taiwan has increased from 1.07 per 100,000 persons in 2000 to 2.17 per 100,000 persons in 2008 (p < 0.0001). With the median overall survival (OS) time of 0.98 years, 25.0 % of AML patients in this study cohort received best supportive care alone. Compared to the normal population, AML survivors had higher rates of hypertension (hazard ratio [HR] 1.69; 95 % confidence interval [CI] 1.18–2.42; p < 0.01), cardiovascular disease (HR 2.53; 95 % CI 1.39–4.61; p < 0.01), diabetes (HR 2.27; 95 % CI 1.48–3.48; p < 0.001), and psychological disorders (HR 1.45; 95 % CI 1.04–2.04; p < 0.05). Although patients undergoing allo-HSCT had a better OS than did patients treated with intensive chemotherapy alone (median not reached vs. 1.53 years; p < 0.0001), diabetes was found more often among allo-HSCT recipients than among patients receiving intensive chemotherapy only (HR 2.93; 95 % CI 1.21–7.08; p < 0.05).

Conclusion

Regular physical and psychological surveillance of AML survivors is needed especially for those receiving allo-HSCT.

     

Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid

Purpose

This analysis evaluated patient-reported outcomes and analgesic use in patients with bone metastases from solid tumours across three comparative studies of denosumab and zoledronic acid.

Methods

Pooled data were analysed from three identically designed double-blind phase III studies comparing subcutaneous denosumab 120 mg with intravenous zoledronic acid 4 mg monthly in patients with bone metastases from breast cancer (n?=?2,046), castration-resistant prostate cancer (n?=?1,901) or other solid tumours (n?=?1,597). Pain severity, pain interference, health-related quality of life and analgesic use were quantified.

Results

At baseline, approximately half of patients had no/mild pain (53 % [1,386/2,620] denosumab; 50 % [1,297/2,578] zoledronic acid). Denosumab delayed onset of moderate/severe pain by 1.8 months (median, 6.5 vs 4.7 months; hazard ratio, 0.83; 95 % CI, 0.76–0.92; p?<?0.001; 17 % risk reduction) and clinically meaningful increases in overall pain interference by 2.6 months (median, 10.3 vs 7.7 months; hazard ratio, 0.83; 95 % CI, 0.75–0.92; p?<?0.001; 17 % risk reduction) compared with zoledronic acid. Strong opioid use and worsening of health-related quality of life were less common with denosumab.

Conclusions

Across three large studies of patients with advanced solid tumours and bone metastases, denosumab prevented progression of pain severity and pain interference more effectively than zoledronic acid.     

Risk of unplanned visits for colorectal cancer outpatients receiving chemotherapy: a case-crossover study

Aim

This study was conducted to evaluate the impact of chemotherapy on the risk of unplanned visit in a cohort of colorectal cancer outpatients. Chief complaints for unplanned visits and risk factors for hospital admission were also analyzed.

Patients and methods

Clinical data of 229 consecutive colorectal cancer patients who were unexpectedly presented to our acute oncology clinic between 2006 and 2009 were reviewed. A case-crossover statistical analysis was applied to study the association between exposure to chemotherapy (trigger event) and the occurrence of unplanned visit (acute outcome) in three time windows (7, 15, and 21 days from the closest previous chemotherapy treatment). Cox model was used to assess the risk factors for hospitalization.

Results

There were 469 unplanned visits registered. Most of the patients had Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 (80 %) and advanced cancer stage (78 %). The majority of unplanned visits (72 %) occurred within 30 days since last chemotherapy. The most frequent presenting complaints were pain, fatigue, and anorexia. The two time windows associated with higher risk of visit were 15 and 21 days from last treatment, both for early (odds ratio [OR] 3.8, CI 1.4–10.2 and OR 3.8, CI 1.4–10.2) and advanced disease stage (OR 1.71, CI 1–2.9 and OR 3, CI 1.5–5.9). Of the unplanned visits, 10 % resulted in hospital admission. Presenting with multiple symptoms and with deteriorated PS were both predictors for hospitalization.

Conclusion

Chemotherapy exposition triggers the need for unplanned visits over the second and third week after treatment. The prompt and effective management of unexpected events may be cost- and time-saving and reduce pressure on oncology services.     

Effects of adjuvant chemotherapy on recurrence,survival, and quality of life in stage II colon cancer patients: a 24-month follow-up

Purpose

The purpose of this cohort study was to investigate the association of adjuvant chemotherapy with quality of life (QoL), survival, and recurrence over the 24 months following diagnosis in stage II colon cancer patients.

Methods

Overall, 453 patients were recruited from North Carolina from 2009 to 2011 and interviewed with a closed-ended survey detailing quality of life, health behaviors, treatment, and cancer recurrence at three times points: diagnosis, 12-, and 24-months post-diagnosis; mortality was obtained via the National Death Index.

Results

In sum, 265 patients received chemotherapy. Receipt of chemotherapy exhibited an inverse association with total Functional Assessment of Cancer Treatment (FACT)-General (P?<?0.01), FACT-Colorectal (P?<?0.01), physical (P?<?0.01), emotional (P?=?0.02), and functional (P?<?0.01) well-being; the inverse association between receiving chemotherapy and emotional well-being persisted for Caucasians but not African Americans (P _interaction?=?0.049). Those who received chemotherapy demonstrated significantly higher odds of cancer recurrence (odds ratio (OR) 2.74; 95 % confidence interval (CI) 1.18, 6.35) and all-cause mortality (OR: 1.95; 95 % CI: 1.05, 3.62).

Conclusions

In this study, stage II colon cancer patients who received chemotherapy treatment were more likely to have poor QoL, recurrence, and all-cause mortality after 24 months compared to those who did not receive chemotherapy. Future research focusing on subtypes of chemotherapy treatment, as well as a longer follow-up period, is needed.

     

De-escalation of antimicrobial treatment in neutropenic patients with severe sepsis: results from an observational study

Background

In severe sepsis, guidelines recommend de-escalating the empirical antimicrobial treatment as soon as the microbiological results are available. We aimed to determine the rate of de-escalation of the empirical antimicrobial treatment in neutropenic patients with severe sepsis. The characteristics of antimicrobial treatment associated with de-escalation and its impact on short- and long-term survival were also determined.

Methods

In the intensive care unit (ICU) of a cancer referral center, we prospectively collected observational data related to the antimicrobial management in neutropenic patients who developed severe sepsis and were admitted to ICU for at least 48 h. De-escalation of antimicrobial therapy consisted either of deleting one of the empirical antibiotics of a combined treatment, or, whenever possible, to use a betalactam antibiotic with a narrower spectrum of activity. Multivariate logistic regression was conducted to determine the factors associated with de-escalation, while a Cox proportional hazards model with a time-dependent covariate was fitted to assess the effect of de-escalation on 30-day survival. Finally 1-year survival after ICU discharge was compared across de-escalation groups.

Results

Cumulative incidence of de-escalation of the empirical antimicrobial treatment among the 101 patients of the cohort was 44 %, [95 % confidence interval (CI) 38–53 %], including 30 (68 %) patients with ongoing neutropenia. A microbiological documentation was available in 63 (63 %) patients. Factors associated with de-escalation were the adequation of the empirical antimicrobial treatment in ICU [OR = 10.8 (95 % CI 1.20–96)] for adequate documented treatment versus appropriate empirical treatment, the compliance with guidelines regarding the empirical choice of the anti-pseudomonal betalactam [OR = 10.8 (95 % CI 1.3–89.5)]. De-escalation did not significantly modify the hazard of death within the first 30 days [HR = 0.51 (95 % CI 0.20–1.33)], nor within 1 year after ICU discharge [HR = 1.06 (95 % CI 0.54–2.08)].

Conclusion

Our data suggest that, in ICU, de-escalation of the empirical antimicrobial treatment is frequently applied in neutropenic cancer patients with severe sepsis. No evidence of any prognostic impact of this de-escalation was found.     

Oral-transmukosales Fentanylcitrat zur Therapie von Durchbruchschmerzen

Background

In a non-interventional study the efficacy and tolerability of oral transmucosal fentanyl citrate (OTFC) was studied in patients with opioid-treated cancer pain suffering from breakthrough pain.

Patients and methods

The prospective multicenter observational trial included 406 patients. For 3–4 months, efficacy of OTFC treatment for breakthrough pain was documented using a numerical analog pain intensity scale (NAS). Further, OTFC therapy was rated and adverse events were recorded.

Results

With application of oral transmucosal fentanyl citrate median pain intensity fell from NAS 8 points at the beginning to NAS 2 points at the end of the study. The median effective dosage was 400 g. Tolerability was rated as good or very good by 87.5% of the patients.

Conclusion

Oral transmucosal fentanyl citrate is a safe and effective treatment for breakthrough pain in chronic cancer-related pain.