Long-term safety of oral transmucosal fentanyl citrate for breakthrough cancer pain.

This open-label study evaluated the long-term safety and tolerability of oral transmucosal fentanyl citrate (OTFC) in ambulatory cancer patients with breakthrough pain undergoing cancer care at 32 university- or community-based practices. Patients had participated in a previous short-term titration trial of OTFC, were experiencing at least one episode per day of breakthrough pain, and had achieved relief of their breakthrough pain with an opioid. Patients received OTFC units at a starting dosage strength determined in the short-term trial (200-1600 microg). Outcome measures included number of successfully treated breakthrough pains, global satisfaction rating (0 = poor through 4 = excellent), and side effects. In total, 41,766 units of OTFC were used to treat 38,595 episodes of breakthrough pain in 155 patients. Number of treatment days ranged from 1 to 423 (mean, 91 days). Patients averaged 2.9 breakthrough pain episodes per day. About 92% of episodes were successfully treated with OTFC and there was no trend toward decreased effectiveness over time. Most patients (61%) did not require dose escalation during treatment. Global satisfaction ratings were consistently above 3, indicating very good to excellent relief. Common adverse events associated with OTFC were somnolence (9%), constipation (8%), nausea (8%), dizziness (8%), and vomiting (5%). Six patients (4%) discontinued therapy due to an OTFC-related adverse event. There were no reports of abuse and no concerns about the safety of the drug raised by patients or families. OTFC was used safely and effectively during long-term treatment of breakthrough pain in cancer patients at home.

Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study.

Oral transmucosal fentanyl citrate (OTFC) is a novel opioid formulation in which the potent synthetic mu-agonist fentanyl is embedded in a sweetened matrix that is dissolved in the mouth. It is undergoing investigation as a treatment for cancer-related breakthrough pain, a prevalent phenomenon defined as a transitory flare of moderate to severe pain that interrupts otherwise controlled persistent pain. There have been no controlled trials of other treatments for this condition. To evaluate the safety and efficacy of ascending doses of OTFC, a novel controlled dose titration methodology was developed that applied blinding and randomization procedures to the evaluation of recurrent pains in the home environment. The study was a multicenter, randomized, double-blind dose titration study in ambulatory cancer patients. The sample comprised adult patients receiving a scheduled oral opioid regimen equivalent to 60-1000 mg oral morphine per day, who were experiencing at least one episode per day of breakthrough pain and had achieved at least partial relief of this pain by use of an oral opioid rescue dose. After collection of 2 days of baseline data concerning the efficacy of the usual rescue drug, patients were randomly treated with either 200 or 400 microg OTFC unit doses in double-blind fashion. Up to two breakthrough pains each day could be treated with up to four OTFC unit doses per pain. OTFC in unit doses containing 200, 400, 600, 800, 1200 or 1600 microg of fentanyl citrate were available for the study. The unit dose was titrated upward in steps until the patient had 2 consecutive days on which breakthrough pain could be treated with the single unit dose, titration was ineffective at a 1600 microg unit dose, or 20 days elapsed. To maintain the double-blind, orders to titrate up were ignored one-third of the time according to a pre-defined randomization schedule accessible only to an unblinded study pharmacist. Main outcome measures included, numeric or categorical measures of pain intensity, pain relief, and global assessment of drug performance. Dose response relationships were found suggesting that the methodology was sensitive to opioid effects. Seventy-four percent of patients were successfully titrated. There was no relationship between the total daily dose of the fixed schedule opioid regimen and the dose of OTFC required to manage the breakthrough pain. Although the study was not designed to provide a definitive comparison between OTFC and the usual rescue drug, exploratory analyses found that OTFC provided significantly greater analgesic effect at 15, 30 and 60 min, and a more rapid onset of effect, than the usual rescue drug. Adverse effects of the OTFC were typically opioid-related, specifically somnolence, nausea and dizziness. Very few adverse events were severe or serious. This study demonstrated the feasibility of controlled trial methodology in studies of breakthrough pain. OTFC appears to be a safe and effective therapy for breakthrough pain, and dose titration can usually identify a unit dose capable of providing adequate analgesia. If the lack of a relationship between the effective OTFC dose and fixed schedule opioid regimen is confirmed, dose titration may be needed in the clinical use of this formulation. Further investigation of OTFC as a specific treatment for breakthrough pain is warranted.

Quality of life of women with ovarian cancer.

The primary objectives of this study were to determine the nature and extent of physical problems and psychological distress experienced by women with ovarian cancer and to identify medical and sociodemographic factors that were predictive of distress. Quality of life was assessed at 3-month intervals, for a maximum of 12 months in 151 ovarian cancer patients, most with advanced-stage disease (86%). Patients' pain, other physical symptoms, level of physical functioning, psychological state, and social functioning were evaluated using the following measures: a detailed pain questionnaire, Memorial Pain Assessment Card, Memorial Symptom Assessment Scale, Mental Health Inventory (MHI), Functional Living Index--Cancer (FLIC), and the Karnofsky Performance Status. Upon entry, 33% of patients reported significant psychological distress, as indicated by MHI Psychological Distress scores (MHI-PD) equal or greater to 1.5 standard deviations above the mean of a nationwide community sample. Impaired physical functioning (FLIC subscale) was the most important predictor of heightened psychological distress (MHI-PD) at baseline (1.5 SD or greater above the norm) (P = 0.0004) in a stepwise logistic regression involving medical/physical and sociodemographic variables as predictors. Further, significant differences were found in all quality of life scales between patients with Karnofsky Performance Status scores of < or = 80, and those with ratings of 90 or greater (P = 0.036 to P < 0.0001). These data suggest the need for an improved and more frequent assessment of ovarian cancer patients' psychological status, particularly as physical functioning declines, to improve early detection and referral to treatment of those suffering from psychiatric sequelae of cancer.

Pain in ovarian cancer patients. Prevalence, characteristics, and associated symptoms.

BACKGROUND: The prevalence, characteristics, and impact of pain and other symptoms have not been studied systematically in women with ovarian cancer. Anecdotally, pain has been associated with the onset of the disease and is a common problem among those with advanced cancer; symptoms other than pain appear to be highly prevalent. Given the profound influence of pain and other symptoms on quality of life, the evaluation of these phenomena could provide data relevant to the clinical management of these patients and advance quality of life research in the area of symptom assessment. METHODS: Questionnaires were completed by 111 inpatients and 40 outpatients with ovarian cancer who were undergoing treatment at a cancer center. Measures included a comprehensive pain questionnaire; the Rand Mental Health Inventory, Functional Living Index--Cancer; and the Memorial Symptom Assessment Scale. RESULTS: The sample (N = 151) represented 74% of the eligible patients. The median age was 55 years (range, 23-86), 82% had Stage III or IV disease at presentation, and 69% had active disease at the time of the survey. Pain, fatigue, and psychologic distress were the most prevalent symptoms. Sixty-two percent (N = 94) described a pain syndrome that preceded the onset or recurrence of the disease, and 42% (N = 63) reported "persistent or frequent pain" during the preceding 2 weeks. The latter pain had a median duration of 2 weeks (range, less than 1 to 756 weeks) and usually was in the abdominopelvic region (80%), frequent or almost constant (66%), and moderate to severe. Most patients reported moderate or greater pain-related interference with various aspects of function, particularly activity (68%), mood (62%), work (62%), and overall enjoyment of life (61%). Performance status, inpatient status, and unmarried status were significant predictors of pain presence or intensity, and both performance status and extent of tumor were significant predictors of pain interference with function. CONCLUSIONS: Among those with ovarian cancer, greater than 40% experienced pain that substantially undetermined function in one half to two thirds of these patients. Impaired performance status is associated most strongly with pain. The onset or recurrence of disease often is heralded by a stereotypic pain syndrome.