Badi El Osta

Donepezil for Cancer Fatigue: A Double-Blind, Randomized, Placebo-Controlled Trial

PURPOSE To evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F). PATIENTS AND METHODS Patients with fatigue score >or= 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) for more than 1 week were included. Patients were randomly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days. A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level. All patients were offered open-label donepezil during the second week. FACIT-F and/or the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 11, and 15. The FACIT-F fatigue subscale score on day 8 was considered the primary end point. RESULTS Of 142 patients randomly assigned to treatment, 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis. Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .57) or ESAS (P = .18) between groups. In the open-label phase, fatigue intensity continued to be low as compared with baseline. No significant toxicities were observed. CONCLUSION Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue.

Comparison of symptom burden among patients referred to palliative care with hematologic malignancies versus those with solid tumors.

BACKGROUND Patients with hematologic malignancies have reduced and later access to palliative care services (APCS) than do those with solid tumors. It is unclear whether these patients develop a high symptom burden at the end of life that requires special palliative care interventions. The purposes of this retrospective study were to determine whether symptoms are less severe in patients with hematologic than in those with solid malignancies on APCS and whether symptom severity is associated with early APCS. METHODS We studied the records of consecutive patients with hematologic and solid malignancies at their first palliative care consultation (PC1). We collected information about demographics, cancer type, date of PC1, and the interval from PC1 to death (PC1-D). We reviewed the charts for the Edmonton Symptoms Assessment System (ESAS) and presence of delirium. RESULTS We included 250 patients (125 with each type of malignancy). Median pain and drowsiness were 4 (3-5) and 7 (5-10) among hematologic compared to 5 (4-6, p=0.043) and 5 (3-6, p=0.0008) among patients with solid malignancies, respectively. Delirium was detected in 51 of 125 (41%) hematologic versus 20 of 125 (16%) solid (p=0.0001). Median PC1-D was 13 days for hematologic versus 46 days for solid (p=0.0001). There was no correlation between PC1-D and pain (r= -0.117, p=0.4 for hematologic and r=0.09, p=0.37 for solid), dyspnea (r= -0.02, p=0.85 for hematologic and r=0.09, p=0.42 for solid) or the Symptom Distress Score (r= -0.047, p=0.72 for hematologic and r= -0.093, p=0.32 for solid). CONCLUSIONS Hematologic patients had increased delirium and drowsiness and later APCS The overall symptom severity was similar in both groups of patients and did not correlate with early APCS. Future prospective studies are needed to better define APCS patterns in this group.

Alcoholism Screening in Patients with Advanced Cancer: Impact on Symptom Burden and Opioid Use

PURPOSE Alcoholism is a devastating disease that can cause patient and family suffering and is frequently underdiagnosed. Preliminary studies suggest that it is associated with increased symptom expression and opioid dose escalation. The CAGE questionnaire is a widely used tool for alcoholism screening. The purpose of this study was to determine the frequency and characteristics of patients who screen positive for alcoholism in a palliative care outpatient clinic (PCOC). METHODS We reviewed 665 consecutive charts of patients referred to the PCOC and collected data regarding age, gender, and type of cancer. For the first 100 consecutive CAGE positive (CAGE+) and 100 consecutive CAGE negative (CAGE-) patients, time from advanced cancer diagnosis (AC) to PCOC was calculated, and symptoms (Edmonton Symptom Assessment Scale, ESAS) and Morphine Equivalent Daily Dose (MEDD) were collected. RESULTS CAGE was available for 598 of 665 (90%) patients. Of 598 patients, 100 (17%) were CAGE+. CAGE+ patients were younger (58 versus 60 years, p < 0.05), predominantly male (68% versus 47%, p < 0.0001), and with head/neck malignancies (24% versus 9%, p < 0.05). CAGE+ patients were referred earlier (5 +/- 27 months after AC, p < 0.0001). At baseline, pain, sleep, dyspnea, well-being, and total symptom distress were significantly worse among CAGE+ patients. Both groups showed similar improvement in symptoms. CAGE+ patients were more frequently on opioids upon referral (47/100 versus 29/100, p < 0.05) and follow-up (27/65 versus 16/68, p < 0.05). At follow-up, opioid doses did not show significant changes. CONCLUSION Seventeen percent of the patients were CAGE+. These patients were referred earlier to palliative care, had more symptom expression, and were more frequently on opioids. The palliative care team successfully improved symptom control in both groups without opioid dose escalation.

The Effect of Oral Methadone on the QTc Interval in Advanced Cancer Patients: A Prospective Pilot Study

BACKGROUND Recent reports suggest that high doses of methadone may prolong QTc interval and occasionally cause torsades de pointes; however, few of these studies involved the palliative care population. OBJECTIVE The purpose of this study was to determine the effect of initiation of methadone on QTc interval in patients with cancer pain seen at the palliative care setting. METHODS We enrolled 100 patients with cancer in this prospective study. Patients were followed clinically and electrocardiographically for QTc changes at baseline, 2, 4, and 8 weeks. Contributing factors for QTc prolongation such as medications, cardiovascular diseases, and electrolytes disturbances were documented. QTc prolongation was defined as greater than 430 ms in males and greater than 450 ms in females, and significant QTc prolongation was defined as QTc interval greater than 25% increase from baseline or 500 ms or more. RESULTS Electrocardiographic (ECG) assessments were available for 100, 64, 41, and 27 patients at baseline, 2-, 4-, and 8-week follow-up, respectively. At baseline prior to initiation of methadone, 28 (28%) patients had QTc prolongation. Clinically significant increase in QTc occurred in only 1 of 64 (1.6%) patients at week 2, and none at weeks 4 and 8. There was no clinical evidence of torsades de pointes, ventricular fibrillation, or sudden death. QTc prolongation was more frequent among patients with increased baseline QTc interval. CONCLUSIONS Baseline QTc prolongation was common, whereas significant QTc interval 500 ms or more after methadone initiation rarely occurred, with no evidence of clinically significant arrhythmias. This study supports the safety of methadone use for pain control in patients with advanced cancer in the palliative care setting.

METHADONE INITIATION AND ROTATION IN THE OUTPATIENT SETTING FOR PATIENTS WITH CANCER PAIN

Methadone is an effective and inexpensive opioid for cancer pain treatment. It has been reported as difficult to use in the outpatient setting because of its variable relative potency and long half‐life. The purpose of this study was to determine the outcome of methadone initiation or rotation for cancer pain treatment in outpatient settings.

The influence of tumor necrosis factor-α -308 G/A and IL-6- 174 G/C on pain and analgesia response in lung cancer patients receiving supportive care

Introduction: We previously showed that select cytokine gene polymorphisms are a significant predictor for pain reported at initial presentation in 446 white patients newly diagnosed with non–small cell lung cancer. This follow-up study explores the extent to which polymorphisms in tumor necrosis factor-α (TNF- α-308 G/A), interleukin (IL)-6 −174G/C, and IL-8 −251T/A could explain variability in pain and analgesic response among those patients (n = 140) subsequently referred for pain treatment. Methods: Pain severity (0, no pain; 10, worst pain) was assessed at initial consultation and at follow-up visit. The total dose of opioids at the time of first-follow up visit (30 days postconsult) was converted to an equivalent dose of parenteral morphine. Results: Forty-one percent (57 of 140) of the patients reported severe pain (score >7/10) at initial consultation (mean, 5.5), which significantly decreased to 25% (mean, 4) at first follow-up visit (McNemar = P < 0.001). Polymorphisms in TNF and IL-6 were significantly associated with pain severity (for TNF GG, 4.12; GA, 5.38; AA, 5.50; P = 0.04) and with morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P = 0.004), respectively. Adjusting for demographic and clinical variables, variant alleles in TNFα −308 G/A remained significantly associated with pain severity (b = 0.226; P = 0.036) and carriers of the IL-6 −174C/C genotypes required 4.7 times higher dose of opioids for pain relief (odds ratio, 4.7; 95% confidence interval, 1.2;15.0) relative to GG and GC genotypes. Conclusions: We provide preliminary evidence of the influence of cytokine genes on pain and response to analgesia in lung cancer patients. Additional studies are needed to validate our findings. The long-term application is to tailored pain therapies. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3262–7)

Characteristics of patients who refuse do-not-resuscitate orders upon admission to an acute palliative care unit in a comprehensive cancer center

Refusal of appropriately indicated do‐not‐resuscitate (DNR) orders may cause harm and distress for patients, families, and the medical team. We conducted a retrospective study to determine the frequency and predictors of refusals of DNR in advanced cancer patients admitted to an acute palliative care unit.

Opioids masquerading as delirium in a patient with cancer pain and obstructive sleep apnea.

IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA, intrathecal and epidural opioids can easily precipitate drowsiness and respiratory depression, sometimes resulting in death.1,2 However, to our knowledge there have been no reports of delirium in patients with obstructive sleep apnea who are taking oral and parenteral opioids for pain control. Delirium is a common and sometimes overlooked complication in patients with cancer; it has been estimated to affect 45%–85% of patients with advanced cancer,3 but it is reversible in 50% of episodes, especially if caused by opioids, psychoactive drugs, or dehydration.4 Here, we report the first known case of a patient with obstructive sleep apnea who developed delirium after taking opioids for cancer pain management. After suspecting obstructive sleep apnea to be the main cause, we successfully treated the delirium with a continuous positive airway pressure (CPAP) mask. This case brings to light the association between obstructive sleep apnea and sensitivity to opioids and reemphasizes the need for good history taking to assess and treat obstructive sleep apnea before instituting opioids for pain control.

Innovative Strategies for Decreasing Blood Collection Wait Times for Patients in Early-Phase Cancer Clinical Trials

PURPOSE Long wait times are a primary source of dissatisfaction among patients enrolled in early-phase clinical trials. We hypothesized that an automated patient check-in system with readily available display for increasing awareness of waiting intervals would improve patient flow and use of our rooms, with decreased turnover time and increased throughput. METHODS We recorded in-room wait times for patients seen in our clinic and observed the logistics involved in the blood collection process to delineate causes for delays. We then implemented a three-step strategy to alleviate the causes of these delays: (1) changing the collection of materials and the review of faxed orders, (2) improving our LabTracker automated database system that included wait time calculators and real-time information regarding patient status, and (3) streamlining lower complexity appointments. RESULTS After our intervention, we observed a 19% decrease in mean wait times and a 30% decrease in wait times among patients waiting the longest (95th percentile). We also observed an increase in staff productivity during this process. Modifications in LabTracker provided the biggest reduction in mean wait times (17%). CONCLUSION We observed a significant decrease in mean wait times after implementing our intervention. This decrease led to increased staff productivity and cost savings. Once wait times became a measurable metric, we were able to identify causes for delays and improve our operations, which can be performed in any patient care facility.

New tools for enhancing the quality of phase I clinical trials: The Armada and Labtracker computer systems.

235 Background: The MD Anderson Clinical and Translational Research Center (CTRC) focuses on Phase I and early Phase II clinical trials and is managing approximately 156 studies annually. This 18-room combined treatment and laboratory unit manages an average of 12,500 research pharmacologic time points and over 3,000 individual shipments yearly. In FY12, 74% of shipments were done on the day of collection (DOC), whereas 26% of the shipments were shipped periodically as required by the corresponding protocol. All studies are monitored at each step for errors - minor (simple DOC label corrections) or major (improper or missed specimen). Activity is analyzed and reported monthly. METHODS In 2010, to ensure accuracy of timing, collection method, proper storage, specimen condition, and destination accuracy, we developed a robust proprietary Oracle-based laboratory tracking system (LabTracker). In addition, we designed an Advanced Research Management and Data Analysis interface (ARMADA) which provides daily step by step protocol guidance using an innovative color-icon touch-screen display of all required protocol activities for patients in the CTRC. LabTracker contains all auditable items required in the clinical trial and markedly reduces work duplication and handwritten data transcription. We hypothesized that this input system would help decrease errors and improve research quality. RESULTS In FY10 there were 2,506 DOC shipments with an overall error rate of 3.07%. In FY12 errors decreased to 1.31% out of 3,128 DOC shipments. In FY10, there were 14,507 timepoints with 28 major errors (0.19%). In 2012, with 13,490 timepoints, major errors decreased to 19 (0.076%). LabTracker database also supports billing and has catalogued over 275,000 samples. This system provides real-time accounting and has revolutionized the quality control system of the CTRC as well as the research finance component with 98% charge capture efficiency within 30 days. CONCLUSIONS The LabTracker/ARMADA systems are high volume phase I protocol management tools which have improved quality, decreased redundant work, and support a real time financial management system for complex phase I clinical trials.