Hypoglycemia during rapid methadone dose escalation.

OBJECTIVES: To answer a question whether or not rapid methadone dose increase can be associated with onset of hypoglycemia. This hypothesis is based on the previously reported case reports of hypoglycemia with rapid methadone increase and our clinical experience of a number of cases when symptomatic hypoglycemia during rapid methadone escalation was initially mistaken for methadone overdose. METHODS: A retrospective chart review of 59 consecutive opioid-tolerant patients with cancer who received methadone for pain while inpatients in a tertiary cancer center within 1 year was performed. In patients who also had hypoglycemia during the admission, blood glucose levels were analyzed in relationship to the time of methadone titration. Use of steroid, presence of fever, renal insufficiency, and periods of fasting were recorded. RESULTS: Eleven patients (19 percent) had hypoglycemia while receiving methadone, of them two patients had at least two episodes of hypoglycemia. In the 11 cases of documented hypoglycemia, mean methadone dose was nearly doubled (92 percent increase) within 2 days before the onset of hypoglycemia. None of the other recorded factors correlated with glucose level in this group of patients. CONCLUSIONS: Present report is the first reported series of patients with hypoglycemic episodes associated with rapid methadone dose escalation. Based on our results, a patient who develops unexplained sweating, palpitations, or lethargy during methadone titration may benefit from blood glucose monitoring.

The successful use of parenteral methadone in a patient with a prolonged QTc interval.

Recent case reports have raised concerns about the potential for methadone to prolong the QTc interval (QT corrected for heart rate) and predispose patients to torsade de pointes (TdP), a life-threatening arrhythmia. We present a case report that describes the successful use of parenteral and oral methadone in a patient with uncontrolled cancer pain and a history of QTc prolongation. We describe an approach to the use of methadone in this patient and review both case reports and recent prospective studies that have evaluated the risk of TdP and the long-term outcome with respect to the development of TdP in patients receiving methadone for chronic pain or addiction.

Phase II trial of ixabepilone in patients with cisplatin-refractory germ cell tumors.

In a phase I study, ixabepilone, a novel non-taxane microtubule-stabilizing agent, demonstrated activity against both paclitaxel-sensitive and paclitaxel-refractory solid tumors. We conducted a phase II trial of this agent in patients with advanced germ cell tumors (GCT) who were resistant to conventional therapies. Patients with cisplatin-refractory GCT were enrolled in this single-institution, phase II trial. Ixabepilone was administered at a dose of 40 mg/m2 intravenously over 3 hours every 21 days. Dose modifications were planned according to a nomogram for adverse events. Responses were assessed every 6 weeks using tumor markers and radiographic imaging according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients who progressed (>or=20% increase in tumor size or rising serum tumor markers) were taken off protocol. Twenty-nine cycles of treatment were administered to 12 patients. The most common Grade 3/4 toxicities were leukopenia, lymphopenia, and neutropenia. One patient (8%) achieved a confirmed objective partial response but this patient had not received prior treatment with a taxane. Based on slow accrual and a lack of antitumor activity in patients previously treated with a taxane, the trial was closed after enrolling 12 patients. For patients who had previously received taxane therapy, ixabepilone was not efficacious in the treatment of cisplatin-refractory GCT.

Methadone in the treatment of pain and terminal delirum in advanced cancer patients.

OBJECTIVE: This prospective study documents the use of methadone as part of an opioid rotation strategy in patients with uncontrolled pain and severe delirium admitted for terminal care to a tertiary cancer palliative care hospital. METHODS: We reviewed the treatment of 20 patients with severe pain and delirium at the end of life who's delirium did not improve 24 h or longer after starting a neuroleptic medication. RESULTS: Ten male and 10 female patients, 47 to 77 years old, were rotated or "switched" to methadone due to uncontrolled pain in the setting of delirium, limiting further opioid dose escalation. At 2 weeks, a total of 10 patients had expired. Of the 10 patients who were alive 2 weeks after starting methadone, 7 patients were stable on an average of 1.1 mg/h methadone, 2 patients were restarted on morphine IV and one on Percocet. The calculated average equianalgesic dose of methadone was 9% (2%-17%) of the previous morphine-equivalent dose. Of the 20 patients who were switched to methadone for what appeared to be terminal delirium, the pain control was significant in 15, moderate in 3, and unchanged in 2 patients. Average analgesia was good to excellent (average Numeric Analog Scale rating [NAS] decreased from 8.2 to 2.5). Sedation had decreased from 1.65 to 0.55 on a scale of 0 to 3. Of the 20 patients, improvement of cognitive status was significant in 9, moderate in 6, partial in 2, and none in 3 patients. The Memorial Delirium Assessment Scale (MDAS) showed improvement from an average of 23.6 prior to the switch to 10.6 3 days after. Decreased alertness on methadone was devoid of agitated features. SIGNIFICANCE OF RESULTS: Our study suggests that methadone can be effective in the treatment of both refractory pain and what appears to be terminal delirium. Most patients in our group had at least a short-term improvement in mental status as well as significant and lasting improvement in analgesia.

Benefit-risk assessment of transdermal fentanyl for the treatment of chronic pain.

Transdermal fentanyl is effective and well tolerated for the treatment of chronic pain caused by malignancy and non-malignant conditions when administered according to the manufacturer's recommendations. Compared with oral opioids, the advantages of transdermal fentanyl include a lower incidence and impact of adverse effects (constipation, nausea and vomiting, and daytime drowsiness), a higher degree of patient satisfaction, improved quality of life, improved convenience and compliance resulting from administration every 72 hours, and decreased use of rescue medication. Transdermal fentanyl is a useful analgesic for cancer patients who are unable to swallow or have gastrointestinal problems. Transdermal fentanyl forms a depot within the upper skin layers before entering the microcirculation. Therapeutic blood levels are attained 12-16 hours after patch application and decrease slowly with a half-life of 16-22 hours following removal. Patients with chronic pain should be titrated to adequate relief with short-acting oral or parenteral opioids prior to the initiation of transdermal fentanyl in order to prevent exacerbations of pain or opioid-related adverse effects. Transdermal fentanyl can then be initiated based on the 24-hour opioid requirement once adequate analgesia has been achieved. The prolonged elimination of transdermal fentanyl can become problematic if patients develop opioid-related adverse effects, especially hypoventilation. Adverse effects do not improve immediately after patch removal and may take many hours to resolve. Patients who experience opioid-related toxicity associated with respiratory depression should be treated immediately with an opioid antagonist such as naloxone and closely monitored for at least 24 hours. Because of the short half-life of naloxone, sequential doses or a continuous infusion of the opioid antagonist may be necessary. Transdermal fentanyl should be administered cautiously to patients with pre-existing conditions such as emphysema that may predispose them to the development of hypoventilation. Transdermal fentanyl is indicated only for patients who require continuous opioid administration for the treatment of chronic pain that cannot be managed with other medications. It is contraindicated in the management of acute and postoperative pain, as pain may decrease more rapidly in these circumstances than fentanyl blood levels can be adjusted, leading to the development of life-threatening hypoventilation. Cognitive and physical impairments such as confusion and abnormal co-ordination can occur with transdermal fentanyl. Therefore, patients should be instructed to refrain from driving or operating machinery immediately following the initiation of transdermal fentanyl, or after any dosage increase. Patients may resume such activities once the absence of these potential adverse effects is documented.

Chordoid glioma: report of a case with unusual histologic features, ultrastructural study and review of the literature.

Chordoid gliomas are an uncommon primary brain tumor with histologic features of a chordoma and immunolabeling for glial fibrillary acid protein. We report the 32nd case with a review of the literature. The clinical, radiographic and pathologic features of the tumor are presented with new pathologic findings adding support that this lesion may be of ependymal origin. Treatment and long term outcome are limited but chordoid gliomas appear to be indolent lesions that may be cured with gross total resection.

Intraventricular morphine administration for control of chronic cancer pain.

Twenty cancer patients with severe chronic pain have been treated with intraventricular morphine sulfate. Adequate pain relief until death was achieved in 10 patients; 1 patient has been treated for 9 months and is still being treated. In 2 patients, the effects of the morphine sulfate on their unilateral pelvic pain wore off after 4 and 6 months because of tumor progression. At that time, they underwent chordotomy procedures elsewhere. The treatment was discontinued in 4 patients for reasons other than inadequate pain relief, such as medical complications or resolution of pain. In 3 patients, the procedure was abandoned when emotional and psychological factors interfered with pain control. Dose requirements of intraventricular morphine sulfate varied greatly, depending on the total daily dose of systemic narcotic intake at the onset of the study. Intraventricular morphine sulfate is a feasible and reliable method to achieve pain relief in selected cancer patients with severe chronic pain when the maximum tolerated dose of systemic narcotic analgesics has become insufficient to control their pain.