A comparison of patient and proxy symptom assessments in advanced cancer patients.

The purpose of this study was to compare patient and proxy (physician and nurse) assessments of symptoms in advanced cancer patients. The sample consisted of 49 patients with advanced cancer admitted to an acute palliative care unit. Three independent assessments were completed for each patient on two occasions within 11 days of admission. On each occasion, symptoms were rated independently by the patient and two proxies (treating physician and nurse), using the Edmonton Symptom Assessment System (ESAS). The ESAS is a nine-item visual analogue scale (VAS) for assessing pain, activity, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath. Symptom ratings were compared using a repeated-measures ANOVA procedure and correlations. Average physician ratings were generally lower than average patient ratings for both occasions. Average nurse ratings agreed more closely with patient ratings, with a trend towards lower ratings on occasion 1 and higher ratings on occasion 2. There was a significant rater (person rating the effects) effect (P < 0.01) for three of the nine symptoms: physicians rated drowsiness, shortness of breath and pain significantly lower than patients. For drowsiness and shortness of breath, these differences were clinically relevant, representing a difference of more than 12 mm on a 100-mm VAS. The accuracy of assessments amongst those rating the symptoms did not improve over time. Proxy assessments of symptom intensity, particularly by physicians, were significantly lower than patient assessments for three of the nine symptoms. Further research regarding the reliability of patient and proxy assessments is needed to assess and manage symptoms in advanced cancer effectively.

Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study.

PURPOSE: To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer. METHODS: A total of 84 patients with advanced, solid tumours not responsive to hormone therapy were enrolled in this double-blind, crossover study. During phase 1, patients were randomly assigned to receive megestrol acetate (160 mg 3 times daily) for 10 days or placebo. During phase 2, after a 2-day washout period, patients received the alternate treatment for 10 days. Patients underwent daily assessments of activity, nausea, appetite and well-being by means of a visual analogue scale (VAS). In addition, nutritional status (weight, tricep skinfold measure, arm muscle circumference), energy intake, fatigue (Piper Fatigue Scale) and quality of life (Functional Living Index-Cancer [FLIC]) were assessed. RESULTS: Among the 53 evaluable patients megestrol acetate resulted in a significant improvement in appetite (p = 0.005), activity (p = 0.007) and well-being (p = 0.03). There was no significant change in the intensity of nausea, nutritional parameters, energy intake or FLIC scores. There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score. Upon completion of the study, while still blind to the treatment condition, 30 patients indicated that they felt better overall after megestrol, 15 said they felt better after placebo, and 10 indicated no preference (p = 0.001). CONCLUSION: Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported. The effects are not secondary to nutritional changes. The FLIC quality-of-life questionnaire was unable to detect these changes.

Comparison of two different concentrations of hyaluronidase in patients receiving one-hour infusions of hypodermoclysis.

The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per one-half liter to 150 units per one-half liter in patients receiving brief infusions for subcutaneous hydration. Twenty-five evaluable patients were randomized to receive a local injection of 300 units of hyaluronidase or 150 units of hyaluronidase immediately before two 1-hr infusions of two-thirds dextrose 5% and one-third normal saline solution (500 cc volume). The following day a crossover took place, and patients received the alternate treatment before each of the two 1-hr infusions. The intensity and swelling as reported by the patient (visual analogue scale 0-100), and the intensity of edema and rash as assessed by the investigator (score 0-4) were not significantly different between groups. The patients' and investigators' final choice was also not significantly different. Patients could not distinguish between bolus and their previous experience with overnight clysis. Our results suggest that brief infusions are well tolerated for subcutaneous hydration of patients with advanced cancer. A concentration of 150 units of hyaluronidase per one-half liter is well tolerated in this population.

Steady-state pharmacokinetic evaluation of a novel, controlled-release morphine suppository and subcutaneous morphine in cancer pain.

Although the oral route is the preferred method for morphine administration for cancer pain, many patients will require an alternate route of administration at some point during their illness. The authors studied the steady-state pharmacokinetics of morphine after administration of a novel, controlled-release suppository (MS-CRS) and subcutaneous morphine in a randomized, double-blind, two-way crossover evaluation in 10 patients with cancer pain. When administered at a 2.5:1 analgesic ratio, MS-CRS given every 12 hours showed an equivalent extent of absorption compared with subcutaneous morphine given every 4 hours (AUC0-12, 132.5 +/- 30.1 versus 123.8 +/- 27.3 ng.h.mL-1, P = not significant [NS]). Peak morphine concentrations were lower, time of peak was later, and percent fluctuation less after MS-CRS than after subcutaneous morphine (Cmax, 14.7 +/- 2.9 versus 29.9 +/- 5.4 ng/mL, P = .0110; tmax, 3.33 +/- 0.75 versus 2.22 +/- 0.15 hours, P = .0160; fluctuation, 122 +/- 71 versus 356 +/- 123%, P = .00160). Relative bioavailability of MS-CRS using the 2.5:1 analgesic ratio was 105%, and bioavailability from data dose normalized without regard to route specificity in metabolism was 42%. For both routes of administration there was a significant linear relationship between morphine dose and AUC (MS-CRS, r = .8568, P = .0032; subcutaneous morphine, r = .8314, P = .0055). MS-CRS morphine provides a pharmacokinetic profile consistent with dosing every 12 hours; at steady state, the extent of absorption is comparable with that of subcutaneous morphine when administered at a 2.5:1 dose ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical efficacy and safety of a novel controlled-release morphine suppository and subcutaneous morphine in cancer pain: a randomized evaluation.

PURPOSE: A significant number of cancer patients will require an alternate route of morphine administration at some point during their illness. This study compared the clinical efficacy and safety of a novel morphine sulfate controlled-release suppository (MS-CRS) and subcutaneous (SC) morphine in patients with cancer pain. METHODS: Thirty patients with cancer pain were randomized in a double-blind crossover study to MS-CRS every 12 hours or SC morphine every 4 hours for 4 days each, using a 2.5:1 analgesic equivalence ratio. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed with a VAS. Evaluations were made by the patient at 8 AM, noon, 4 PM, and 8 PM and rescue morphine consumption recorded. RESULTS: Twenty-three patients completed the study (13 men and 10 women; mean age, 64.0 +/- 2.0 years) and were treated with mean daily MS-CRS and SC morphine doses of 326 +/- 69 mg and 138 +/- 28 mg, respectively. There was a small but significant difference in overall ordinal pain-intensity scores in favor of MS-CRS (0.7 +/- 0.1 v 0.9 +/- 0.1, P = .0459). There were no significant differences between MS-CRS and SC morphine in overall VAS scores for pain intensity (13 +/- 3 v 13 +/- 3 mm), sedation (23 +/- 3 v 25 +/- 4 mm), and nausea (8 +/- 2 v 9 +/- 2 mm). The mean daily rescue analgesic consumption during MS-CRS and SC morphine did not differ significantly (1.2 +/- 0.4 v 1.2 +/- 0.4 doses/d). CONCLUSION: MS-CRS, administered every 12 hours, provides analgesia comparable to SC morphine and represents a reliable, noninvasive alternative method of pain control for patients unable to take oral morphine.

Comparison of the efficacy, safety, and pharmacokinetics of controlled release and immediate release metoclopramide for the management of chronic nausea in patients with advanced cancer.

BACKGROUND: The short elimination half-life of metoclopramide necessitates frequent administration for optimal relief of nausea. This study compares a newly developed controlled release preparation of metoclopramide (CRM) and immediate release metoclopramide (IRM) with respect to efficacy, safety, and pharmacokinetics in patients with chronic nausea associated with advanced cancer. METHODS: Thirty-four patients with advanced cancer with nausea lasting more than 1 month and with no evidence of involvement of the gastrointestinal tract, peptic ulcer or gastritis, brain metastases, or metabolic abnormalities were randomized, in a double-blind cross-over study, to receive 40 mg of CRM every 12 hours or 20 mg of IRM every 6 hours for 3 days. Nausea, food intake, and side effects were assessed four times daily. On Day 3, sequential venous samples were taken (12 patients) to determine plasma metoclopramide concentrations. RESULTS: In 29 evaluable patients, the intensity of nausea on Day 3, measured by a 0-100-mm visual analogue scale and 0-3 categoric scale was 15 +/- 17 and 0.6 +/- 0.6 after IRM, versus 8 +/- 9 (P = 0.033) and 0.4 +/- 0.5 (P = 0.055) after CRM, respectively. Visual analogue scale nausea scores recorded by time of day and by day for the 3 treatment days were significantly lower for patients who received CRM compared with those who received IRM (P = 0.047 and P = 0.043, respectively), but categoric nausea scores were not significantly different between treatments by time of day and by day across the 3 treatment days. No differences were observed in caloric intake or side effects between treatments. In a pharmacokinetic analysis, the CRM/IRM ratio for area under the curve0-12 (microgram x hours x L-1), Cmax (microgram/L), and Tmax (hours) was 100%, 98%, and 2.3 fold, respectively. CONCLUSION: Controlled release metoclopramide is safe and effective in managing chronic nausea in patients with advanced cancer. Future studies should focus on characterizing this syndrome more clearly and on determining the optimal dose of metoclopramide and the effects of drug combinations that have proven to be useful in managing chemotherapy-induced emesis (i.e., metoclopramide plus corticosteroids).

The use of hypodermoclysis for rehydration in terminally ill cancer patients.

The need to treat dehydration in terminally ill patients to minimize symptom distress remains a controversial issue. Hypodermoclysis (HDC) is a simple technique for rehydration that offers many advantages over the intravenous route. In this prospective open study of 100 consecutive patients who died on a palliative care unit, we recorded our indications for, and use of, HDC. Of the 100 patients, 69 received HDC for an average of 14 +/- 18 days during an average admission of 35 +/- 41 days. The 31 patients who did not receive HDC had an average admission of 22 +/- 24 days, and appeared to have different characteristics than the HDC group. HDC was well tolerated in most patients at an average volume of 1203 +/- 505 mL/day. These results confirm that HDC for dehydration is a safe and effective technique and suggest the need for further research to clarify the role of rehydration in assisting symptom control.

Symptom control in terminally ill patients with malignant bowel obstruction (MBO).

The inadequacy of prolonged conservative management with nasogastric suction and intravenous fluids for terminally ill patients with bowel obstruction has long been recognized. Using previous reports and our experience on the Palliative Care Unit at the Edmonton General Hospital, we have developed a basic approach to bowel obstruction management. In a review of 100 consecutive patients who died on our Palliative Care Unit, 15 required medical management for bowel obstruction. Evaluation of these cases suggests that intensive medical management can provide good symptom control without using intravenous lines and with minimal use of nasogastric tubes.

Use of the Edmonton Injector for parenteral opioid management of cancer pain: a study of 100 consecutive patients.

In this retrospective study, we reviewed the patterns of use of the Edmonton Injector (EI) in 100 consecutive cancer patients. Seventy-eight patients used the EI for an average of 23 +/- 27 days. The main reasons for starting the EI were nausea (37 patients) and severe pain (31 patients). The median opioid dose equivalent to parenteral morphine (MEDD) was 264 +/- 443 mg/day. The mean duration of the subcutaneous injection site was 6.5 +/- 9.2 days. The most frequent reasons for change were accidental needle pulling (59%) and erythema (12%). Only two patients developed local infection (1% of 196 sites). The average cost of treatment was $1.65 Canadian per patient per day. No mechanical problems or refusals to start or continue treatment were detected. We conclude that the EI is a safe and simple device that allows for cost-effective parenteral administration of opioids for cancer pain.