Catheter-based Techniques for Terminal Cancer Pain: A Review of Nonneuraxial Interventions with Clinical Implications for End-of-Life Pain Management.

BACKGROUND: Evidence suggests that a significant proportion of terminal cancer patients have uncontrolled or inadequately controlled pain when using the World Health Organization (WHO) analgesic ladder approach. The use of interventional techniques has proven to reduce pain that is refractory to conventional methods. However, despite the use of well-established techniques (e.g., intrathecal drug delivery, celiac plexus blocks, etc), nonneuraxial, catheter-based techniques remain underutilized. OBJECTIVE: The purpose of this narrative review is to examine the evidence for nonneuraxial, catheter-based techniques in treating terminal cancer pain, the barriers to implementation, and its role in bridging the gap between single shot techniques and surgically implanted devices. STUDY DESIGN: This is a narrative review article summarizing case reports, case series, retrospective studies, prospective studies, and review articles published at any time frame on the use of nonneuraxial, catheter-based techniques for the treatment of cancer pain in the end-of-life setting. SETTING: The University of Texas MD Anderson Cancer Center. METHODS: A literature search was conducted from November 2020 to January 2021 using the PubMed database and keywords related to nonneuraxial catheters, terminal cancer pain, and hospice. All English-based literature published at any time frame involving human patients was included. RESULTS: The number of studies referencing the use of nonneuraxial, catheter-based techniques for the treatment of terminal cancer pain is limited (n = 25). All of these studies were small, single-center, nonrandomized, noncontrolled case series and case reports. A total of 63 patients were evaluated across all studies, with the largest study involving 12 patients. The most common medication used was monotherapy with bupivacaine or ropivacaine and the longest duration of continuous catheter usage was 217 days. Of the studies that reported outcomes, the majority reported a reduction in pain. Very few studies reported catheter-related adverse events and tunneling appeared to be an important factor in reducing complications. LIMITATIONS: No studies were available comparing the use of nonneuraxial, catheter-based techniques to conventional systemic medical management. Further, the studies in this review were heterogenous and limited to a small sample sizes reported in case reports and case series only. CONCLUSION: Nonneuraxial, catheter-based techniques have the potential to play a significant role in the treatment of terminal cancer pain. Despite limited data, initial findings indicate that nonneuraxial, catheter-based techniques have the potential to bridge the gap between single shot interventions and surgical implanted devices by providing an effective, continuous therapy, with a lower risk profile.

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial.

CONTEXT: The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. OBJECTIVES: We examined the effect of two doses of prophylactic FSS on exertional dyspnea. METHODS: In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35%-45% (high dose) or 15%-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. RESULTS: Thirty of the 50 enrolled patients completed the study. High-dose FSS (n = 13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P = 0.007) and greater walk distance (mean change 44 m; P = 0.001) compared to baseline. Low-dose FSS (n = 17) resulted in a nonsignificant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P = 0.24) and significant increase in walk distance (mean change 24 m; P = 0.01) compared to baseline. Global evaluation showed high-dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P = 0.06). No significant adverse events or detriment to vital signs or neurocognitive function was detected. CONCLUSION: Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High-dose FSS should be tested in confirmatory trials.

Sacroiliac joint pain following iliac-bone marrow aspiration and biopsy: a cohort study.

Background: Sacroiliac joint (SIJ) pain is a common source of lower back pain; the factors associated have not been studied in cancer patients. Observing patients with bone marrow aspiration and biopsy (BMAB) who subsequently developed SIJ-pain led to this investigation. Aim: To investigate this possible relationship. Methods: A cohort study of cancer patients diagnosed with SIJ pain. The association of BMAB with SIJ pain was evaluated, as were variables that differed between the groups. Results: The prevalence of SIJ pain was 4.95% (231/4669). Among 231 patients with SIJ pain, 34% (78/231) did not have prior history of lower back pain and had undergone BMAB prior to their diagnosis of SIJ pain. A statistically significant association between BMAB-SIJ-pain was found (p < 0.01). Conclusion: We found linear correlation between BMAB and subsequent SIJ pain.

The Long-Term Impact of Neurofeedback on Symptom Burden and Interference in Patients With Chronic Chemotherapy-Induced Neuropathy: Analysis of a Randomized Controlled Trial.

CONTEXT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment and may adversely affect quality of life (QOL) for years. OBJECTIVES: We explored the long-term effects of electroencephalographic neurofeedback (NFB) as a treatment for CIPN and other aspects of QOL. METHODS: Seventy-one cancer survivors (mean age 62.5; 87% females) with CIPN were randomized to NFB or to a waitlist control (WLC) group. The NFB group underwent 20 sessions of NFB where rewards were given for voluntary changes in electroencephalography. Measurements of pain, cancer-related symptoms, QOL, sleep, and fatigue were obtained at baseline, end of treatment, and one and four months later. RESULTS: Seventy one participants enrolled in the study. At the end of treatment, 30 in the NFB group and 32 in the WLC group completed assessments; at four months, 23 in the NFB group and 28 in the WLC completed assessments. Linear mixed model analysis revealed significant group × time interaction for pain severity. A general linear model determined that the NFB group had greater improvements in worst pain (primary outcome) and other symptoms such as numbness, cancer-related symptom severity, symptom interference, physical functioning, general health, and fatigue compared with the WLC group at the end of treatment and four months (all P < 0.05). Effect sizes were moderate or large for most measures. CONCLUSION: NFB appears to result in long-term reduction in multiple CIPN symptoms and improved postchemotherapy QOL and fatigue.

Compliance with Opioid Therapy: Distinguishing Clinical Characteristics and Demographics Among Patients with Cancer Pain.

Background: Because an increase of patients who misuse opioids has been identified in our cancer clinical setting through urine drug testing (UDT) and the Screener and Opioid Assessment for Patient's with Pain-Short Form (SOAPP-SF), we conducted this retrospective cohort study to identify patient characteristics that are associated with UDT that indicates noncompliance. Methods: Over a two-year period, 167 of 8,727 patients (2.4%) seen in the pain clinic and who underwent UDT were evaluated to determine compliance with prescribed opioid regimens. Descriptive clinical and demographic data were collected, and group differences based on compliance with opioid therapy were evaluated. Results: Fifty-eight percent of the patients were noncompliant with their prescribed opioid therapy. Noncompliant patients were younger than compliant patients, with a median age of 46 vs 49 years (P = 0.0408). Noncompliant patients were more likely to have higher morphine equivalent daily doses; however, the difference was not statistically significant. Patients with a history of alcohol (ETOH) (P = 0.0332), illicit drug use (P = 0.1014), and smoking (P = 0.4184) were more likely noncompliant. Univariate regression analysis showed that a history of ETOH use (P = 0.034), a history of anxiety (P = 0.027), younger age (P = 0.07), and a SOAPP-SF score of 4 or higher (P = 0.05) were associated with an abnormal UDT. Conclusions: History of ETOH use, anxiety, high SOAPP-SF score, and younger age were associated with UDT that indicates noncompliance. Given the very small percentage of UDT testing, it is quite likely that a significant number of patients who did not undergo UDT were also nonadherent with treatment recommendations.

Randomized controlled trial of neurofeedback on chemotherapy-induced peripheral neuropathy: A pilot study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study examined whether electroencephalogram (EEG) neurofeedback (NFB) could alleviate CIPN symptoms in survivors. METHODS: This was a randomized controlled trial with survivors assigned to an NFB group or a wait-list control (WLC) group. The NFB group underwent 20 sessions of NFB, in which visual and auditory rewards were given for voluntary changes in EEGs. The Brief Pain Inventory (BPI) worst-pain item was the primary outcome. The BPI, the Pain Quality Assessment Scale, and EEGs were collected before NFB and again after treatment. Outcomes were assessed with general linear modeling. RESULTS: Cancer survivors with CIPN (average duration of symptoms, 25.3 mo), who were mostly female and had a mean age of 62.5 years, were recruited between April 2011 and September 2014. One hundred percent of the participants starting the NFB program completed it (30 in the NFB group and 32 in the WLC group). The NFB group demonstrated greater improvement than the controls on the BPI worst-pain item (mean change score, -2.43 [95% confidence interval, -3.58 to -1.28] vs 0.09 [95% confidence interval, -0.72 to -0.90]; P =·.001; effect size, 0.83). CONCLUSIONS: NFB appears to be effective at reducing CIPN symptoms. There was evidence of neurological changes in the cortical location and in the bandwidth targeted by the intervention, and changes in EEG activity were predictive of symptom reduction. Cancer 2017;123:1989-1997. © 2017 American Cancer Society.

Acupuncture for treatment of uncontrolled pain in cancer patients: a pragmatic pilot study.

PURPOSE: Pain control is an ongoing challenge in the oncology setting. Prior to implementing a large randomized trial at our institution, we investigated the feasibility, safety, and initial efficacy of acupuncture for uncontrolled pain among cancer patients. HYPOTHESES: Our hypotheses were that the acupuncture treatments provided would be ( : ) feasible, ( : ) safe, and ( : ) a beneficial adjunct to pain management. STUDY DESIGN: This was a single arm, nonrandomized pragmatic pilot study. METHODS: Participants experiencing pain ≥4 on a 0 to 10 numeric rating scale received a maximum of 10 treatments on an individualized basis. Recruitment, attrition, compliance, and adverse events (AEs) were assessed. Pain (Brief Pain Inventory-Short Form), quality of life (MD Anderson Symptom Inventory [MDASI]), and patient satisfaction were assessed at baseline and at the end of treatment. RESULTS: Of 115 patients screened, 52 (45%) were eligible and agreed to participate. Eleven (21%) were lost to follow-up, leaving 41 who completed all study procedures. No AEs were reported. Mean pain SEVERIT: was 6.0 ± 1.3 at baseline and 3.8 ± 2.0 at follow-up ( : < .0001). Pain INTERFERENC: was 6.2 ± 2.3 at baseline and 4.3 ± 2.8 at follow-up ( : < .0011). On the MDASI, the mean symptom SEVERIT: was 4.6 ± 1.8 at baseline and 3.2 ± 1.9 at follow-up ( : < .0001), and mean symptom INTERFERENC: was 5.8 ± 2.4 at baseline and 4.1 ± 2.9 at follow-up ( : < .002). Prescribed pain medications decreased across the course of the study. Patient satisfaction was high: 87% reported that their expectations were met "very well" or "extremely well"; 90% said they were likely to participate again; 95% said they were likely to recommend acupuncture to others; and 90% reported they found the service to be "useful" or "very useful." CONCLUSIONS: Acupuncture was feasible, safe, and a helpful treatment adjunct for cancer patients experiencing uncontrolled pain in this study. Randomized placebo-controlled trials are needed to confirm these results.

Risk stratification of opioid misuse among patients with cancer pain using the SOAPP-SF.

BACKGROUND: Opioids are recognized as an integral part of the armamentarium in the management of cancer pain. There has been a growing awareness of the misuse of prescription opioids among cancer patients. More research is needed to detail risk factors and incidence for opioid misuse among cancer pain patients. METHODS: We reviewed 522 patient charts that were seen in our Pain Center from January 1, 2009 to June 30, 2009 for risk stratification of opioid misuse with demographic and clinical factors utilizing the Screener and Opioid Assessment for Patients with Pain-short form (SOAPP-SF). Group differences based on High (≥4) and Low (<4) SOAPP-SF scores were evaluated at initial visit, follow-up within a month and 6-9 months. RESULTS: One hundred forty-nine of the 522 (29%) patients had a SOAPP-SF score of ≥4. The mean age for patients with high SOAPP-SF score (≥4) was 50 ± 14 vs 56 ± 14 for patients with low SOAPP-SF score (<4) (P < 0.0001). The pain scores were higher for patients with high SOAPP-SF score compared with patients with low SOAPP-SF score at consult (P < 0.0001). Morphine equivalent daily dose (MEDD) was higher for patients with high SOAPP-SF score compared with patients with low SOAPP-SF score at consult (P = 0.0461). Fatigue, feeling of well-being, and poor appetite were higher among the high SOAPP-SF group at initial visit (P < 0.0001, <0.0001, <0.0149, respectively). The high SOAPP-SF score patients also had statistically significant (P < 0.05) higher anxiety and depression scores at all three time points. In the multivariate analysis, patients younger than 55 years have a higher odds of having a "high" SOAPP-SF score than patients 55 years and older {odds ratio (OR) (95% confidence interval [CI]) = 2.76 (1.58, 4.81), P = 0.0003} adjusting for employment status, disease status, treatment status, usual pain score, and morphine equivalency at consult. Patients with higher usual pain score at consult have higher odds of a "high" SOAPP-SF score (OR [95% CI] = 1.34 [1.19, 1.51], P < 0.0001) adjusting for age, employment status, disease status, treatment status, and morphine equivalency at consult. CONCLUSION: Patients classified by the SOAPP-SF in the current study as high risk tended to be younger, endorse more pain, have higher MEDD requirement, and endorse more symptoms of depression and anxiety. These findings are consistent with the literature on risk factors of opioid abuse in chronic pain patients which suggests that certain patient characteristics such as younger age, anxiety, and depression symptomatology are associated with greater risk for opioid misuse. However, a limitation of the current study is that other measures of opioid abuse were not available for validation and comparison with the SOAPP-SF.

Complications after intrathecal drug delivery due to the underlying malignancy in two patients with intractable cancer pain.

Intrathecal drug delivery is a mode of analgesic delivery that can be considered in those experiencing both refractory pain and excessive side effects from opioid and adjuvant analgesic use. Delivery of analgesic agents directly to the cerebral spinal fluid allows binding of the drug to receptors at the spinal level. Therefore, a reduced analgesic dosage can be afforded, resulting in reduction of drug side effects due to decreased systemic absorption. Drug delivery into the intrathecal space provides this benefit, yet it does not eliminate the possibility of drug side effects or risks of complications. Complications from this route of administration may be seen in the perioperative period or beyond, including infection, inflammatory mass, bleeding, and catheter or pump dysfunction, among others. This may manifest as new/worsening pain or as a neurologic deficit, such as a sensorimotor change and bladder/bowel dysfunction. Urgent evaluation with a detailed physical examination, device interrogation, and other workup including imaging is called for if symptoms suspicious for device-related problems arise. For the cancer pain patient, the underlying malignancy should also be considered as a potential cause for these new symptoms after intrathecal system implantation. We present 2 such cases of complications in the cancer pain patient after intrathecal drug delivery due to progression of the underlying malignant process rather than to surgical or device-related problems. The first patient had a history of metastatic osteosarcoma who, shortly after undergoing an intrathecal drug delivery trial with external pump, presented with new symptoms of both pain and neurologic changes. The second patient with a history of chondrosarcoma developed new symptoms of pain and sensorimotor change several days after intrathecal drug delivery system implantation.

Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine.

PURPOSE: Chemoneuropathy remains a painful, burdensome complication of cancer treatment for patients receiving a range of chemotherapeutics, yet the cause and persistence of this condition are not fully documented. This study was designed to quantify the longevity of and contributions to neuropathy following treatment with the plant alkaloids paclitaxel and vincristine. METHODS: Quantitative sensory testing was conducted approximately 18 months apart on 14 patients, seven of which had been treated with paclitaxel and seven with vincristine and compared to data from 18 healthy control subjects. In addition, skin biopsies were obtained to investigate changes in the density of Meissner's corpuscles and epidermal nerve fibers (ENFs), the loss of which is thought to contribute to multiple forms of neuropathy. RESULTS: Impairments in motor skills, as measured by a grooved peg-board, were found. Deficits in touch detection were observed using von Frey monofilaments, as were changes in sharpness detection using a weighted needle device. Using a Peltier device, warmth and heat detection were impaired. These deficits were consistent across time. Remarkably, the average length of time patients reported painful neuropathy was over four and a half years. Skin biopsies were found to be deficient in Meissner's corpuscles and ENFs. CONCLUSIONS: The combination of widespread deficits in sensory testing and decreases in skin innervation for cancer patients receiving paclitaxel or vincristine document a persistent polyneuropathy which severely impacts these patients. Decreases in Meissner's corpuscles and ENFs indicate a possible mechanism for the neuropathy.

Distinguishing features of cancer patients who smoke: pain, symptom burden, and risk for opioid misuse.

UNLABELLED: Although many cancer patients who have pain are smokers, the extent of their symptom burden and risk for opioid misuse are not well understood. In this study we analyzed records of patients being treated for cancer pain, 94 of whom were smokers and 392 of whom were nonsmokers, to determine smoking status group differences. Smokers had significantly higher pain intensity, fatigue, depression, and anxiety than nonsmokers (independent samples t-tests P < .002). Smokers were at higher risk for opioid misuse based on the short form of the Screener and Opioid Assessment for Patients with Pain (SOAPP). Specifically, smokers had more frequent problems with mood swings, taking medications other than how they are prescribed, a history of illegal drug use, and a history of legal problems (chi-square tests P ≤ .002). Changes in pain and opioid use were examined in a subset of patients (146 nonsmokers and 46 smokers) who were receiving opioid therapy on at least 2 of the 3 data time points (consult, follow-up 1 month after consult, follow-up 6 to 9 months after consult). Results based on multilevel linear modeling showed that over a period of approximately 6 months, smokers continued to report significantly higher pain than nonsmokers. Both smokers and nonsmokers reported a significant decline in pain across the 6-month period; the rate of decline did not differ across smokers and nonsmokers. No significant difference over time was found in opioid use between smokers and nonsmokers. These findings will guide subsequent studies and inform clinical practice, particularly the relevancy of smoking cessation. PERSPECTIVE: This article describes pain, symptom burden, and risk for opioid misuse among cancer patients with pain across smoking status. Smoking appears to be a potential mechanism for having an increased pain and symptom burden and risk for opioid misuse. This improved understanding of cancer pain will inform clinical practice.

Opioid abuse in cancer pain: report of two cases and presentation of an algorithm of multidisciplinary care.

BACKGROUND: The growing awareness of opioid abuse and addiction in the chronic pain population, along with increasing cancer survivorship, has heightened our awareness of this potential problem in the cancer patient. An increasing number of patients who abuse opioids have been identified in our clinical setting. OBJECTIVE: We present an algorithm of multidisciplinary care for the treatment of cancer patients at risk for abusing opioids. SETTING: Two illustrative patient examples were identified recently from our clinic. RESULTS: These 2 patient examples demonstrate our multidisciplinary approach to treatment. A discussion of safe prescribing principles adapted from the literature is presented. Also, a brief point of added complexity is introduced; specifically, ethical considerations due to the unique nature of cancer pain. LIMITATIONS: Although validation studies exist for the use of screening tools in patients with chronic noncancer pain, there have been no instrument validation studies on patients with cancer pain. The educational treatment model that we refer to regarding facilitating safe use of opioids also has not been studied on patients with cancer pain. Lastly, we express caution in generalizing our guidelines to patients with noncancer pain. Our patient population differs in the multiple co-existing stressors and symptom burden associated with cancer. CONCLUSIONS: We have become increasingly aware of the problem of opioid abuse in the cancer pain population. With an approach to using safe prescribing principles adapted from chronic pain literature, and an ethically based multidisciplinary approach, clinicians can continue to treat pain successfully in the opioid-misusing cancer patient. We outline our approach in this article.

Follow-up psychophysical studies in bortezomib-related chemoneuropathy patients.

UNLABELLED: Many frontline chemotherapeutic agents produce robust neuropathy as a dose-limiting side effect; however, the persistence of chemotherapy-related sensory disturbances and pain are not well documented. We have previously investigated the qualities of bortezomib-induced pain, and now seek to determine the ongoing nature of this pain. Twenty-six control subjects and 11 patients who had previously been treated with bortezomib and who were experiencing ongoing pain consented to recurring quantitative sensory testing. A pilot immunohistochemistry study of skin innervation was also performed on patient-obtained biopsies. Psychophysical testing in patients revealed persistent changes including decreased skin temperature in the area of pain, diminished touch and sharpness detection, increased pegboard completion times, and decreased sensitivity to skin heating. Additionally, the intensity of pain, as captured by the use of a visual analog scale and pain descriptors, was reported by patients to be unchanged during the retest despite similar morphine equivalent daily doses. The patient skin biopsies displayed a marked decrease in the density of epidermal nerve fibers and Meissner's corpuscles. These results signify a persistent and severe impairment of Aß, Aδ, and C fibers in patients with chronic bortezomib-induced chemoneuropathy. Further, this study reports a loss of both epidermal nerve fibers and Meissner's corpuscles. PERSPECTIVE: The results of this article indicate a persistent, painful peripheral neuropathy in patients treated with bortezomib. Pilot data indicates a loss of nerve fibers innervating the area of pain. This is the first paper to address the persistence, and potential contributing factors, of bortezomib chemoneuropathy.

Preliminary evaluation of an educational model for promoting positive team attitudes and functioning among pain medicine fellows.

OBJECTIVE: In response to the Accreditation Council for Graduate Medical Education's (ACGME) new pain medicine fellowship requirement, which emphasizes multidisciplinary training strategies aimed at providing improved clinical care for pain patients, we developed a multidisciplinary team training education model for trainees in our institution's Fellowship Program in Pain Medicine. Although the biopsychosocial model guides the delivery of care by multidisciplinary pain teams, there is a gap on how to improve team attitudes and functioning within an already extensive pain medicine curriculum. The current study aimed to fill that gap by developing and incorporating an educational model that focuses on interpersonal relationships among team members and strategies for improving team performance over time. DESIGN, SETTING, PARTICIPANTS, INTERVENTION, AND OUTCOME MEASURES: Here, we provide a brief overview of our institution's pain medicine fellowship training program highlighting how we have included a team training component into lectures, interdisciplinary case conferences, and journal club articles that focus on topics in the ACGME pain medicine curriculum. We present data from a team attitude and functioning assessment battery administered to 11 pain medicine fellows at the outset and end of their fellowship. RESULTS AND CONCLUSIONS: Mean assessment scores increased from the beginning of the fellowship to the end of the fellowship on interdisciplinary pain team knowledge, current team skills, and attitude toward health care teams. The current study demonstrated effective ways for assessing team attitudes and functioning and including this educational component into a 1-year pain medicine curriculum. Based on our results, we will continue to teach and model effective teamwork in an effort to enhance our trainees' attitudes toward working on an interdisciplinary pain team.

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.

Case studies in breakthrough pain.

OBJECTIVE: To illustrate the variable presentations of and treatments for breakthrough pain (BTP). DESIGN: Five cases of BTP were selected by the author, and treatment options were then considered. RESULTS: Breakthrough pain presents in many different ways in clinical practice. Clinicians must first evaluate patients to identify the subtype, etiology, severity, and pattern of BTP, and then use that information to suggest appropriate interventions. Whenever possible, correctable causes of BTP should first be addressed. A variety of treatment tools are available, including opioid analgesics, nonopioid analgesics, adjuvant agents, nonpharmacologic strategies, and procedural and surgical interventions. In many cases, more than one treatment option will be appropriate, but in all cases, regular communication between patient and clinician will be needed to achieve optimal control of BTP. CONCLUSION: Treatment of BTP should be individualized by using a multidisciplinary approach to address each patient's pain profile.

Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial.

PURPOSE: To evaluate the effectiveness of patient-controlled methylphenidate as 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 a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point. RESULTS: Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed. CONCLUSION: Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention.

Oral transmucosal fentanyl citrate in the outpatient management of severe cancer pain crises: a retrospective case series.

OBJECTIVE: This retrospective chart review evaluated the efficacy of oral transmucosal fentanyl citrate (OTFC) in an outpatient cancer pain center for patients experiencing severe exacerbations of pain that exceed usual breakthrough pain levels. PATIENTS: Records were reviewed for all patients who received OTFC at M.D. Anderson's outpatient pain clinic over a three-month time period. OTFC was used in thirty-nine patients experiencing a recent onset of severe pain (> or =7 on a 0-10 scale). All patients had cancer, cancer-related pain syndromes, and were opioid tolerant with an oral morphine equivalent daily dosage (MEDD) of (> or =40 mg/day. RESULTS: Prior to OTFC treatment, all patients reported a mean pain intensity of 9.0 (SD = 1.2). After OTFC treatment, patients reported a mean intensity of 3.0 (SD = 1.4), a significant reduction in pain intensity (P < 0.001). In most cases, OTFC averted the need for an emergency center visit, parenteral opioids, and hospital admission, which suggests that OTFC may be an effective alternative over intravenous opioids to rapidly titrate analgesia in selected opioid-tolerant cancer patients experiencing severe pain.