Errors in opioid prescribing: a prospective survey in cancer pain.

CONTEXT: Cancer pain is debilitating and has multidimensional consequences. It can be treated adequately in up to 90% of patients by following pain management guidelines. Nevertheless, inadequate pain control remains a global problem. OBJECTIVES: We surveyed prescribing patterns in patients referred to our Palliative Medicine Program (PMP) to identify common errors in opioid use. METHODS: Consecutive cancer patients seen by our PMP were prospectively surveyed for the presence of pain and errors in opioid prescribing at the time of initial consultation. Our recommendations to correct and optimize pain management also were recorded. RESULTS: One hundred eighty-six consecutive cancer patients were screened. One hundred seventeen (63%) had cancer pain, 151 opioid prescribing errors were detected, and 147 different recommendations were made. Most common were failure to order around-the-clock opioids for constant pain, and the failure to treat or prevent opioid side effects. Multiple errors were more common in females, but the sex difference did not reach statistical significance. There was no difference in the errors by pain severity or reason for consultation. CONCLUSION: Opioid prescribing errors were common. Females may be at greater risk of multiple errors. A PM consultation program is effective in identifying and correcting a wide variety of opioid prescribing errors.

Opioid equianalgesic tables: are they all equally dangerous?

Pain is one of the most common symptoms in cancer patients. Opioids are widely prescribed for this and other purposes. Properly used, they are safe, but they have serious and potentially lethal side effects. Successful use of opioids to manage cancer pain requires adequate knowledge about opioid pharmacology and equianalgesia for the purpose of both drug rotation and route conversion. The aim of this study was to demonstrate variations in equianalgesic ratios, as quoted in equianalgesic tables and various educational materials widely available to practicing physicians. We surveyed commercially available educational materials in package inserts, teaching materials provided by pharmaceutical companies, and the Physicians' Desk Reference for equianalgesic tables of commonly used opioids. We found inconsistent and variable equianalgesic ratios recommended for both opioid rotation and conversion. Multiple factors like inter- and intraindividual differences in opioid pharmacology may influence the accuracy of dose calculations, as does the heterogeneity of study design used to derive equianalgesic ratios. Equianalgesic tables should only serve as a general guideline to estimate equivalent opioid doses. Clinical judgment should be used and individual patient characteristics considered when applying any table. Professional organizations and regulators should establish a rotation and conversion consensus concerning opioid equianalgesic ratios. Systematic research on equianalgesic opioid dose calculation is recommended to avoid adverse public health consequences of incorrect or inappropriate dosing. Current information in equianalgesic tables is confusing for physicians, and dangerous to the public.

The business of palliative medicine - part 5: service utilization in a comprehensive integrated program.

The aim of palliative medicine is to provide multidisciplinary comprehensive care in advanced illness. Patient and family utilization of various product service lines offered by the Harry R Horvitz Center for Palliative Medicine at the Cleveland Clinic Foundation was studied. Newly referred patients were followed up prospectively until 85% had either died or been lost to follow-up. Demographic, clinical, and referral data were recorded; subsequent product service line utilization was updated daily. The total study period was 171 days, and 238 patients entered. Acute care inpatient unit, outpatient clinic visits, and 24-hour phone contacts were the most frequently used product service lines. Patients had a median of 3 contacts (range, 1 to 27) with individual service lines. Multiple palliative medicine product service lines were utilized often, with repeated use of the individual service lines. A comprehensive integrated palliative medicine program is necessary to fully meet the complex needs of those with advanced disease.

Thrombocytosis as a prognostic factor for survival in patients with metastatic renal cell carcinoma.

BACKGROUND: It has been suggested that thrombocytosis, as defined by a platelet count >400,000/microL, is a negative predictor for survival among patients with metastatic renal cell carcinoma. However, this has not been a uniform finding. METHODS: To address this issue, retrospective analysis of 700 previously untreated patients entering on institution review board-approved phase 1, 2, or 3 clinical trials in the United States and Europe was conducted between 1982 and 2002. RESULTS: Thrombocytosis was present at study entry in 25% of patients. Median baseline platelet count was 304,000/microL (range, 86-1,420,000/microL). Eighty-seven percent of patients died with a median survival of 13.0 months. Median follow-up for patients not known to have died was 2.4 years. On univariate analysis, patients with elevated platelet counts had significantly shorter survival than patients with normal platelet counts; median survivals of 8.4 and 14.6 months, respectively, P < .001. However, platelet count was associated with several clinical and biochemical factors, including gender, age, performance status, time from diagnosis to study entry, prior radiotherapy or nephrectomy, presence of liver metastasis, number of metastatic sites, amount of hemoglobin, white blood cell count, amount of lactate dehydrogenase, and amount of serum alkaline phosphatase. Several of these factors have previously been reported as prognostic indicators for survival, and, therefore, multivariable analyses were conducted to determine whether thrombocytosis is an independent predictor of survival. After adjusting for multiple factors, thrombocytosis continued to impact negatively on survival, P < .001. CONCLUSIONS: Thrombocytosis was found to be an independent prognostic factor for survival in patients with metastatic renal cell carcinoma.

Targeted therapy for renal cell carcinoma: a new therapeutic paradigm.

Renal cell carcinoma is the most common tumor of the kidney. It has an unpredictable behavior and poor response to systemic therapy. Developing newer therapy for this disease is a priority considering the high recurrence rate and the small subset of patients who benefit from the use of cytokines such as interferon-alpha or interleukin-2. Identifying molecular targets and targeting various biomarkers has revolutionized the therapeutic approach to advanced and metastatic renal cell carcinoma. Although some of the antiangiogenic agents and receptor tyrosine kinase inhibitors appear promising, further understanding of their mechanism of action and the patient population who would benefit most from such agents is still being explored. As numerous targeted agents are entering the clinical investigation arena in a relatively short period of time, newer challenges in renal cell carcinoma therapeutics are emerging. Some of the future challenges in using targeted antineoplastic agents in renal cell carcinoma will include evaluating their long-term safety and benefit, using the particular drug in the appropriate patient population after appropriate stratification and studying the combination of some of these drugs for synergy or additive effects.

Clinical activity of sorafenib and sunitinib in renal cell carcinoma refractory to previous vascular endothelial growth factor-targeted therapy: two case reports.

Sunitinib and sorafenib are multitargeted receptor tyrosine kinase inhibitors of the vascular endothelial growth factor and platelet-derived growth factor receptor families with antiangiogenic and antitumor activity in metastatic renal cell carcinoma. The utility of these agents in patients refractory to previous treatment with the other agent is unknown. We report 2 cases highlighting that efficacy of these agents is possible after failure of the other agent. Further prospective study is needed.

Emerging drugs for renal cell carcinoma.

Renal cell carcinoma (RCC) still represents a therapeutic challenge when patients have advanced or metastatic disease. Treatment using IL-2 and IFN-alpha continues to be the standard of care in patients who are able to tolerate such regimens. Targeted therapy may become the first-line treatment for patients resistant or intolerant to cytokines as new emerging drugs continue to be investigated. Understanding the genetic abnormalities related to the development of RCC (e.g., VHL gene abnormalities) and identifying molecular targets (e.g., epidermal growth factor, vascular endothelial growth factor and carbonic anhydrase IX) are playing a major role in the emergence of these novel agents for the treatment of this malignancy. Overall, these drugs are better tolerated and more acceptable to use by patients than the traditional cytokine-based regimens. The use of oral drugs to treat various malignancies including RCC seems to be the new paradigm of the future. Further understanding of their mechanisms of action and confirmation of their benefits on the clinical outcome is needed.

Phase II study of the efficacy and safety of oral GD0039 in patients with locally advanced or metastatic renal cell carcinoma.

Seventeen patients with locally advanced or metastatic renal cell carcinoma (RCC) were enrolled in this phase II trial. The purpose of the trial was to assess the efficacy of the administration of oral GD0039, and to further assess the pharmacokinetics and pharmacodynamics of this drug. Patients were given an initial dose of 37.5 micro g/kg b.i.d for 3 weeks followed by one week off in each cycle, with the treatment continuing until disease progression or adverse effects. All 17 patients discontinued treatment due to disease progression or toxicity. Adverse events such as fatigue, nausea and diarrhea were common but generally mild. No evidence of anti-tumor activity of GD0039 was seen in this study.

Extensor hallucis longus innervation: an anatomic study.

Thirty legs from skeletally mature embalmed cadavers were dissected to define the most common pattern and the variants of innervation of the extensor hallucis longus muscle and its clinical significance. Twenty-seven muscles had only one innervating branch (90%). Only three muscles had two innervating branches (10%). Twenty-one of the branches entered the muscles from the fibular side (63.6%), six entered the muscles from the tibial side (18.2%), and six entered the muscles from the anterior edge (18.2%). The branches innervating the extensor hallucis longus from the fibular side had a closer relation with the fibular periosteum than those entering the muscle from the tibial side or the anterior edge. The mean length of these branches between their points of origin and entry in the extensor hallucis longus was 5.0 +/- 1.5 cm. The high risk zone for the iatrogenic injury to the muscular branch of the extensor hallucis longus was located between 5.9 +/- 1.7 and 10.9 +/- 1.7 cm inferior to the most distal palpable point of the fibular head. The current study confirmed that the extensor hallucis longus was supplied mostly by one nerve that usually entered the muscle from the fibular side and had a close relation to the fibular periosteum in the dangerous zone.