Cancer pain management.

BACKGROUND: Controlling pain in cancer patients is often inadequate. A recent multicenter study of patients with metastatic disease who were experiencing pain reported that 36% still had pain severe enough to compromise their daily function. METHODS: The author draws on his experiences as well as those of others to review general guidelines and provide specific recommendations for cancer pain management. RESULTS: Three components are critical to managing cancer pain: assessing pain, establishing an appropriate therapeutic opioid regimen, and integrating with other therapies. An appropriate therapeutic opioid regimen involves initiating, consolidating and maintaining therapy. Other strategies (e.g., advanced pharmacological, adjuvant, interventional, and psychological) can be added to opioid therapy. CONCLUSIONS: A revision of the Agency for Health Care Policy and Research Cancer Pain Guidelines is currently underway. The management of pain in cancer patients should include more frequent reassessment of both analgesia and side effects to ensure optimal cancer pain relief.

Amitriptyline-associated seizures in a toddler with Munchausen-by-proxy.

We describe an unusual case of a toddler diagnosed with an idiopathic seizure disorder that later was proved to be caused by deliberate administration of amitriptyline by his custodian. In spite of seizures associated with widened electrocardiographic wave (QRS) and right axis deviation on the electrocardiogram (EKG), the correct diagnosis eluded clinicians through a series of hospital admissions. Unfortunately, clinicians are quite accustomed to the fact that patients previously diagnosed with epilepsy have seizures and may not investigate other causes of seizure. This allowed classic signs of cyclic antidepressant poisoning to go unrecognized.

Palliative medicine in the elderly.

Cancer is primarily a disease of the elderly and the palliation of both disease- and treatment-related symptoms is of importance in the practice of cancer medicine in all patients. Many older patients are treated within community hospitals, in which anticancer therapies are less likely to be given and in which the palliation of symptoms should be of primary importance. Many oncologists struggle with the palliation of symptoms in patients who are near the end of life. This is despite the considerable energies that are spent in palliating symptoms in patients who are receiving anticancer therapies at all disease stages. The management of pain has advanced considerably recently with improvements in pain assessment and pharmacologic interventions. However, elderly patients are less likely than younger patients to receive proper pain management. Elderly patients also are less likely to take opioids for pain because of their attitudes and beliefs. Fatigue, dyspnea, and psychologic issues also are of importance in the management of elderly cancer patients both during anticancer therapy and near the time of death. Some elderly cancer patients die in the care of a hospice, although many are not referred to this service. There are many barriers to the provision of palliative medicine and these may be related to health practitioners, to the patients themselves, or to the health care system of which they are part. The increased educational efforts of health professionals are needed to ensure that all patients, including the elderly, have adequate palliation of their cancer-related symptoms.

A phase I study of 5-fluorouracil, leucovorin and levamisole.

PURPOSE: The activity of 5-fluorouracil (5-FU) against colon cancer is enhanced by leucovorin and the combination of 5-FU and levamisole has activity in the adjuvant treatment of colonic malignancies. The combination of 5-FU with both leucovorin and levamisole may provide additional benefit in the treatment of colon cancer. METHODS: A phase I study to assess qualitative and quantitative toxicities of this three-drug combination and to determine a dose for further phase II testing was undertaken. The role of levamisole as an immunomodulator was also assessed. RESULTS: A group of 38 patients with incurable metastatic malignancies received 119 cycles of treatment at eight dose levels. 5-FU (375 mg/m2 per day) and leucovorin (200 mg/m2 per day) were administered intravenously (days 1-5). Levamisole was administered orally (days 1-3 and 15-17) at doses from 30 to 470 mg/m2 per day. Patients received both 5FU/leucovorin and 5-FU/leucovorin/levamisole in random order for their initial two cycles. All subsequent treatments were with the three-drug combination. Toxicities included nausea, vomiting, stomatitis, thrombocytopenia and granulocytopenia. Diarrhea was the dose-limiting toxicity at 470 mg/m2 per day levamisole. The addition of levamisole resulted in more toxicity than 5-FU and leucovorin alone. No clinical responses were seen with this regimen. The addition of levamisole resulted in more immunomodulation than 5-FU and leucovorin alone as evidenced by release of neopterin from monocytes. CONCLUSION: With this schedule and dose of 5-FU and leucovorin, the maximum tolerated dose of levamisole was 354 mg/m2. However, given the lack of response and the absence of dose-dependent immunomodulation, this may not be the appropriate dose for further phase 11 studies.

Plasma concentrations and renal clearance of morphine, morphine-3-glucuronide and morphine-6-glucuronide in cancer patients receiving morphine.

The plasma concentrations and renal clearance values of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were determined in 11 adult cancer patients maintained on a long term oral morphine dosage (10 to 100mg every 4h). Concentrations in plasma and urine were determined by a specific high performance liquid chromatography assay. In this group of patients, whose creatinine clearance values ranged from 52 to 180 ml/min (3.12 to 10.8 L/h), average steady-state plasma concentrations of morphine, M3G and M6G were related (p < 0.01) to the morphine dose per kilogram of bodyweight. The mean total urinary recovery as morphine, M3G and M6G was 74.6 +/- 26.5% of the dose. Renal clearance values for M3G and M6G were closely related (r2 = 0.80; p < 0.0005). It was not possible to detect a relationship between the renal clearance of morphine, M3G and M6G, and that of creatinine. The renal tubular handling of all 3 compounds showed wide interindividual variation, and there was evidence of either net renal tubular secretion or reabsorption. There was no apparent relationship between plasma morphine and M6G concentrations and pain relief.